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Sample records for antifungal drugs posaconazole

  1. Effectiveness of Posaconazole in Recalcitrant Fungal Keratitis Resistant to Conventional Antifungal Drugs

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    A. Altun

    2014-01-01

    Full Text Available Purpose. To present the success of posaconazole in two cases with recalcitrant fugal keratitis that were resistant to conventional antifungal drugs. Method. We presented two cases that were treated with posaconazole after the failure of fluconazole or voriconazole, amphotericin B, and natamycin therapy. Case 1 was a 62-year-old man with a history of ocular trauma. He had been using topical fluorometholone and tobramycin. His best corrected visual acuity (BCVA was hand motion. He had 5.0 × 4.5 mm area of deep corneal ulcer with stromal infiltration. Case 2 was a 14-year-old contact lens user. He had been using topical moxifloxacin, tobramycin, and cyclopentolate. His BCVA was 20/200. He had a 4.0 × 3.0 mm area of pericentral corneal ulcer with deep corneal stromal infiltration and 2 mm hypopyon. Results. Both patients initially received systemic and topical fluconazole or voriconazole and amphotericin B and topical natamycin that were all ineffective. But the response of posaconazole was significant. After posaconazole, progressive improvement was seen in clinical appearance. BCVA improved to 20/100 in case 1 and 20/40 in case 2. Conclusion. Posaconazole might be an effective treatment option for recalcitrant fusarium keratitis and/or endophthalmitis resistant to conventional antifungal drugs.

  2. Structural characterization of CYP51 from Trypanosoma cruzi and Trypanosoma brucei bound to the antifungal drugs posaconazole and fluconazole.

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    Chiung-Kuang Chen

    Full Text Available BACKGROUND: Chagas Disease is the leading cause of heart failure in Latin America. Current drug therapy is limited by issues of both efficacy and severe side effects. Trypansoma cruzi, the protozoan agent of Chagas Disease, is closely related to two other major global pathogens, Leishmania spp., responsible for leishmaniasis, and Trypansoma brucei, the causative agent of African Sleeping Sickness. Both T. cruzi and Leishmania parasites have an essential requirement for ergosterol, and are thus vulnerable to inhibitors of sterol 14alpha-demethylase (CYP51, which catalyzes the conversion of lanosterol to ergosterol. Clinically employed anti-fungal azoles inhibit ergosterol biosynthesis in fungi, and specific azoles are also effective against both Trypanosoma and Leishmania parasites. However, modification of azoles to enhance efficacy and circumvent potential drug resistance has been problematic for both parasitic and fungal infections due to the lack of structural insights into drug binding. METHODOLOGY/PRINCIPAL FINDINGS: We have determined the crystal structures for CYP51 from T. cruzi (resolutions of 2.35 A and 2.27 A, and from the related pathogen T. brucei (resolutions of 2.7 A and 2.6 A, co-crystallized with the antifungal drugs fluconazole and posaconazole. Remarkably, both drugs adopt multiple conformations when binding the target. The fluconazole 2,4-difluorophenyl ring flips 180 degrees depending on the H-bonding interactions with the BC-loop. The terminus of the long functional tail group of posaconazole is bound loosely in the mouth of the hydrophobic substrate binding tunnel, suggesting that the major contribution of the tail to drug efficacy is for pharmacokinetics rather than in interactions with the target. CONCLUSIONS/SIGNIFICANCE: The structures provide new insights into binding of azoles to CYP51 and mechanisms of potential drug resistance. Our studies define in structural detail the CYP51 therapeutic target in T. cruzi, and

  3. Posaconazole

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    Bhattacharya M

    2010-01-01

    Full Text Available Posaconazole is a novel second-generation Triazole oral antifungal agent. It is highly effective in the prophylaxis of invasive fungal infections in immunocompromised patients. It is used as a first-line agent as well as for salvage therapy in invasive fungal infections including aspergillosis, oropharyngeal and esophageal candidiasis. It has a good adverse effect profile. With the rising incidence of invasive fungal infections due to the HIV pandemic and medical advancements in transplantation and cancer therapy, these features make posaconazole a valuable addition in the family of antifungal agents.

  4. Posaconazole exhibits in vitro and in vivo synergistic antifungal activity with caspofungin or FK506 against Candida albicans.

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    Ying-Lien Chen

    Full Text Available The object of this study was to test whether posaconazole, a broad-spectrum antifungal agent inhibiting ergosterol biosynthesis, exhibits synergy with the β-1,3 glucan synthase inhibitor caspofungin or the calcineurin inhibitor FK506 against the human fungal pathogen Candida albicans. Although current drug treatments for Candida infection are often efficacious, the available antifungal armamentarium may not be keeping pace with the increasing incidence of drug resistant strains. The development of drug combinations or novel antifungal drugs to address emerging drug resistance is therefore of general importance. Combination drug therapies are employed to treat patients with HIV, cancer, or tuberculosis, and has considerable promise in the treatment of fungal infections like cryptococcal meningitis and C. albicans infections. Our studies reported here demonstrate that posaconazole exhibits in vitro synergy with caspofungin or FK506 against drug susceptible or resistant C. albicans strains. Furthermore, these combinations also show in vivo synergy against C. albicans strain SC5314 and its derived echinocandin-resistant mutants, which harbor an S645Y mutation in the CaFks1 β-1,3 glucan synthase drug target, suggesting potential therapeutic applicability for these combinations in the future.

  5. In vitro activity of the antifungal azoles itraconazole and posaconazole against Leishmania amazonensis.

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    Sara Teixeira de Macedo-Silva

    Full Text Available Leishmaniasis, caused by protozoan parasites of the Leishmania genus, is one of the most prevalent neglected tropical diseases. It is endemic in 98 countries, causing considerable morbidity and mortality. Pentavalent antimonials are the first line of treatment for leishmaniasis except in India. In resistant cases, miltefosine, amphotericin B and pentamidine are used. These treatments are unsatisfactory due to toxicity, limited efficacy, high cost and difficult administration. Thus, there is an urgent need to develop drugs that are efficacious, safe, and more accessible to patients. Trypanosomatids, including Leishmania spp. and Trypanosoma cruzi, have an essential requirement for ergosterol and other 24-alkyl sterols, which are absent in mammalian cells. Inhibition of ergosterol biosynthesis is increasingly recognized as a promising target for the development of new chemotherapeutic agents. The aim of this work was to investigate the antiproliferative, physiological and ultrastructural effects against Leishmania amazonensis of itraconazole (ITZ and posaconazole (POSA, two azole antifungal agents that inhibit sterol C14α-demethylase (CYP51. Antiproliferative studies demonstrated potent activity of POSA and ITZ: for promastigotes, the IC50 values were 2.74 µM and 0.44 µM for POSA and ITZ, respectively, and for intracellular amastigotes, the corresponding values were 1.63 µM and 0.08 µM, for both stages after 72 h of treatment. Physiological studies revealed that both inhibitors induced a collapse of the mitochondrial membrane potential (ΔΨm, which was consistent with ultrastructural alterations in the mitochondrion. Intense mitochondrial swelling, disorganization and rupture of mitochondrial membranes were observed by transmission electron microscopy. In addition, accumulation of lipid bodies, appearance of autophagosome-like structures and alterations in the kinetoplast were also observed. In conclusion, our results indicate that ITZ and

  6. Drug-interactions of azole antifungals with selected immunosuppressants in transplant patients: strategies for optimal management in clinical practice

    NARCIS (Netherlands)

    Lempers, V.J.C.; Martial, L.C.; Schreuder, M.F.; Blijlevens, N.M.A.; Burger, D.M.; Aarnoutse, R.E.; Bruggemann, R.J.M.

    2015-01-01

    The management of drug-drug interactions (DDIs) between azole antifungals (fluconazole, itraconazole, posaconazole and voriconazole) and immunosuppressants (cyclosporine, tacrolimus, everolimus and sirolimus) in transplant patients remains challenging, as the impact of altered immunosuppressant conc

  7. Quantification of the Triazole Antifungal Compounds Voriconazole and Posaconazole in Human Serum or Plasma Using Liquid Chromatography Electrospray Tandem Mass Spectrometry (HPLC-ESI-MS/MS).

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    Molinelli, Alejandro R; Rose, Charles H

    2016-01-01

    Voriconazole and posaconazole are triazole antifungal compounds used in the treatment of fungal infections. Therapeutic drug monitoring of both compounds is recommended in order to guide drug dosing to achieve optimal blood concentrations. In this chapter we describe an HPLC-ESI-MS/MS method for the quantification of both compounds in human plasma or serum following a simple specimen preparation procedure. Specimen preparation consists of protein precipitation using methanol and acetonitrile followed by a cleanup step that involves filtration through a cellulose acetate membrane. The specimen is then injected into an HPLC-ESI-MS/MS equipped with a C18 column and separated over an acetonitrile gradient. Quantification of the drugs in the specimen is achieved by comparing the response of the unknown specimen to that of the calibrators in the standard curve using multiple reaction monitoring.

  8. Quantification of the Triazole Antifungal Compounds Voriconazole and Posaconazole in Human Serum or Plasma Using Liquid Chromatography Electrospray Tandem Mass Spectrometry (HPLC-ESI-MS/MS).

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    Molinelli, Alejandro R; Rose, Charles H

    2016-01-01

    Voriconazole and posaconazole are triazole antifungal compounds used in the treatment of fungal infections. Therapeutic drug monitoring of both compounds is recommended in order to guide drug dosing to achieve optimal blood concentrations. In this chapter we describe an HPLC-ESI-MS/MS method for the quantification of both compounds in human plasma or serum following a simple specimen preparation procedure. Specimen preparation consists of protein precipitation using methanol and acetonitrile followed by a cleanup step that involves filtration through a cellulose acetate membrane. The specimen is then injected into an HPLC-ESI-MS/MS equipped with a C18 column and separated over an acetonitrile gradient. Quantification of the drugs in the specimen is achieved by comparing the response of the unknown specimen to that of the calibrators in the standard curve using multiple reaction monitoring. PMID:26660172

  9. Hot Melt Extruded Amorphous Solid Dispersion of Posaconazole with Improved Bioavailability: Investigating Drug-Polymer Miscibility with Advanced Characterisation

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    Ritesh Fule

    2014-01-01

    Full Text Available Invasive antifungal infections are reasons for morbidity and mortality in immunogenic patients worldwide. Posaconazole is a most promising antifungal agent against all types of invasive infections with high % of cure rate. The marketed suspension formulation has low bioavailability and is needed to be taken with food. In this paper, PCZ hot melt extruded amorphous solid dispersion (SD with immediate release and improved bioavailability was prepared using Soluplus (Sol as primary carrier for solubilization. Surfactants such as PEG 400, Lutrol F27, Lutrol F68, and TPGS are also used in combination with Soluplus to improve the physicochemical performance of the formulation when it comes in contact with GI (gastrointestinal fluid. Drug-polymer miscibility of SD was investigated using advanced techniques. In the in vivo study, the AUC(0–72 and Cmax of PCZ/Soluplus were 11.5 and 11.74 time higher than those of pure PCZ. The formulation of the extrudate SD had an AUC(0–72 and Cmax higher than those with the commercial capsule (Noxafil. Molecular dynamic (MD simulation studies were carried out using in silico molecular modelling to understand the drug-polymer intermolecular behaviour. The results of this research ensure enhanced dissolution and bioavailability of the solid dispersion of PCZ prepared by HME compared with the PCZ suspension.

  10. Hot melt extruded amorphous solid dispersion of posaconazole with improved bioavailability: investigating drug-polymer miscibility with advanced characterisation.

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    Fule, Ritesh; Amin, Purnima

    2014-01-01

    Invasive antifungal infections are reasons for morbidity and mortality in immunogenic patients worldwide. Posaconazole is a most promising antifungal agent against all types of invasive infections with high % of cure rate. The marketed suspension formulation has low bioavailability and is needed to be taken with food. In this paper, PCZ hot melt extruded amorphous solid dispersion (SD) with immediate release and improved bioavailability was prepared using Soluplus (Sol) as primary carrier for solubilization. Surfactants such as PEG 400, Lutrol F27, Lutrol F68, and TPGS are also used in combination with Soluplus to improve the physicochemical performance of the formulation when it comes in contact with GI (gastrointestinal) fluid. Drug-polymer miscibility of SD was investigated using advanced techniques. In the in vivo study, the AUC(0-72) and C(max) of PCZ/Soluplus were 11.5 and 11.74 time higher than those of pure PCZ. The formulation of the extrudate SD had an AUC(0-72) and C(max) higher than those with the commercial capsule (Noxafil). Molecular dynamic (MD) simulation studies were carried out using in silico molecular modelling to understand the drug-polymer intermolecular behaviour. The results of this research ensure enhanced dissolution and bioavailability of the solid dispersion of PCZ prepared by HME compared with the PCZ suspension.

  11. 泊沙康唑体内及体外活性研究进展%In-vitro and in-vivo antifungal activities of posaconazole:an update

    Institute of Scientific and Technical Information of China (English)

    孙禾; 苏欣; 施毅

    2011-01-01

    泊沙康唑是广谱三唑类抗真菌新药,对大多数酵母菌和丝状真菌体外高度敏感,如念珠菌属、新型隐球菌、曲霉属、镰刀霉属及接合菌属等.对部分双相型真菌和地方性真菌,泊沙康唑也具有体外活性.对免疫正常及免疫抑制动物的侵袭性感染,泊沙康唑都有广谱、高效的抗真菌活性.对光滑念珠菌、克柔念珠菌、土曲霉、镰刀霉及接合菌等,泊沙康唑的体内外活性优于其他唑类药物.在体内敏感度研究中,对不同免疫状态及不同部位的重度侵袭性感染,泊沙康唑预防和治疗用药都显示了良好的效果.%Posaconazole is a new triazole drug with broad-spectrum activity in vitro against most yeasts and molds such as candidae, cryptococcus neoformans, aspergillus, Fusarium and zygomycetes, and also against certain species of dimorphic fungi and endemic fungi. In immunocompetent or immunocompromised animal models of invasive fungal infections, Posaconazole has been demonstrated to provide highly-effective, broad-spectrum antifungal activities. In-vitro and in-vivo activities of posaconazole were superior to those of other azoles against Candida gla-brata,Candida krusei, Aspergillus terms, fusarium and zygomycetes. In vivo sensitivity studies have shown the promising efficacy of posaconazole against life-threatening fungal infections in animal models with different immune status and sites of infections.

  12. Clinical effectiveness of posaconazole versus fluconazole as antifungal prophylaxis in hematology–oncology patients: a retrospective cohort study

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    Kung, Hsiang-Chi; Johnson, Melissa D; Drew, Richard H; Saha-Chaudhuri, Paramita; Perfect, John R

    2014-01-01

    In preventing invasive fungal disease (IFD) in patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), clinical trials demonstrated efficacy of posaconazole over fluconazole and itraconazole. However, effectiveness of posaconazole has not been investigated in the United States in real-world setting outside the environment of controlled clinical trial. We performed a single-center, retrospective cohort study of 130 evaluable patients ≥18 years of age admitted to Duke University Hospital between 2004 and 2010 who received either posaconazole or fluconazole as prophylaxis during first induction or first reinduction chemotherapy for AML or MDS. The primary endpoint was possible, probable, or definite breakthrough IFD. Baseline characteristics were well balanced between groups, except that posaconazole recipients received reinduction chemotherapy and cytarabine more frequently. IFD occurred in 17/65 (27.0%) in the fluconazole group and in 6/65 (9.2%) in the posaconazole group (P = 0.012). Definite/probable IFDs occurred in 7 (10.8%) and 0 patients (0%), respectively (P = 0.0013). In multivariate analysis, fluconazole prophylaxis and duration of neutropenia were predictors of IFD. Mortality was similar between groups. This study demonstrates superior effectiveness of posaconazole over fluconazole as prophylaxis of IFD in AML and MDS patients. Such superiority did not translate to reductions in 100-day all-cause mortality. PMID:24644249

  13. Clinical effectiveness of posaconazole versus fluconazole as antifungal prophylaxis in hematology–oncology patients: a retrospective cohort study

    International Nuclear Information System (INIS)

    In preventing invasive fungal disease (IFD) in patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS), clinical trials demonstrated efficacy of posaconazole over fluconazole and itraconazole. However, effectiveness of posaconazole has not been investigated in the United States in real-world setting outside the environment of controlled clinical trial. We performed a single-center, retrospective cohort study of 130 evaluable patients ≥18 years of age admitted to Duke University Hospital between 2004 and 2010 who received either posaconazole or fluconazole as prophylaxis during first induction or first reinduction chemotherapy for AML or MDS. The primary endpoint was possible, probable, or definite breakthrough IFD. Baseline characteristics were well balanced between groups, except that posaconazole recipients received reinduction chemotherapy and cytarabine more frequently. IFD occurred in 17/65 (27.0%) in the fluconazole group and in 6/65 (9.2%) in the posaconazole group (P = 0.012). Definite/probable IFDs occurred in 7 (10.8%) and 0 patients (0%), respectively (P = 0.0013). In multivariate analysis, fluconazole prophylaxis and duration of neutropenia were predictors of IFD. Mortality was similar between groups. This study demonstrates superior effectiveness of posaconazole over fluconazole as prophylaxis of IFD in AML and MDS patients. Such superiority did not translate to reductions in 100-day all-cause mortality

  14. Rapid identification of antifungal compounds against Exserohilum rostratum using high throughput drug repurposing screens.

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    Wei Sun

    Full Text Available A recent large outbreak of fungal infections by Exserohilum rostratum from contaminated compounding solutions has highlighted the need to rapidly screen available pharmaceuticals that could be useful in therapy. The present study utilized two newly-developed high throughput assays to screen approved drugs and pharmaceutically active compounds for identification of potential antifungal agents. Several known drugs were found that have potent effects against E. rostratum including the triazole antifungal posaconazole. Posaconazole is likely to be effective against infections involving septic joints and may provide an alternative for refractory central nervous system infections. The anti-E. rostratum activities of several other drugs including bithionol (an anti-parasitic drug, tacrolimus (an immunosuppressive agent and floxuridine (an antimetabolite were also identified from the drug repurposing screens. In addition, activities of other potential antifungal agents against E. rostratum were excluded, which may avoid unnecessary therapeutic trials and reveals the limited therapeutic alternatives for this outbreak. In summary, this study has demonstrated that drug repurposing screens can be quickly conducted within a useful time-frame. This would allow clinical implementation of identified alternative therapeutics and should be considered as part of the initial public health response to new outbreaks or rapidly-emerging microbial pathogens.

  15. 三唑类抗真菌新药泊沙康唑的药理基础%Pharmacokinetic and pharmacodynamic profile of a new triazole antifungal posaconazole

    Institute of Scientific and Technical Information of China (English)

    孙禾; 苏欣; 施毅

    2012-01-01

    Posaconazole oral suspension acts by inhibiting cytochrome P450-dependent-14-ot-demethylase in the biosynthetsis of ergosterol. Since the relative bioavailability is significantly different among regimens, this triazole requires administration with food or a nutritional supplement to assure adequate bioavailability. The extent of protein binding is high (> 98%). The time to reach the maximum plasma concentration is about 5-8 hours following oral administration of a single dose. Posaconazole has a large mean apparent volume of distribution ( VJF) influenced by the dosage regimen, suggesting extensive extravascular distribution and penetration into intracellular spaces. The metabolism of posaconazole is mediated predominantly through phase 2 biotransformations via uridine diphosphate glucuronosyltransferase enzyme pathways. As an inhibitor primarily of CYP3A4, plasma concentrations of drugs that are predominantly metabolized by CYP3A4 may be increased by posaconazole. Posaconazole has a median terminal elimination half-life of 20 - 66 hours and is predominantly eliminated in the feces as unchanged drug. The drug is well tolerated, even in long - term courses. Adverse reactions are generally mild.%泊沙康唑是第二代三唑类抗真菌药,该口服液通过抑制细胞色素P450依赖的14α-脱甲基酶(CYP51)发挥抗真菌活性.泊沙康唑口服生物利用度变异大,随高脂餐同服吸收率最高,分次给药可增加其生物利用度.在体内蛋白结合率达98%,单次给药后5~8h血药浓度达峰.泊沙康唑的表观分布容积与给药方案相关,组织分布广泛,穿透力强,口服给药后7~10d达稳态血药浓度,通过尿苷二磷酸葡萄糖醛酸转移酶途径代谢.泊沙康唑是细胞色素酶CYP3A4的抑制剂,经此通路代谢的药物可受泊沙康唑的影响,血药浓度升高.泊沙康唑主要经消化道清除,清除半衰期20 ~ 66 h,口服耐受性良好,不良反应轻微.

  16. Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections

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    Wiederhold NP

    2015-12-01

    Full Text Available Nathan P Wiederhold Departments of Pathology and Medicine/Infectious Diseases, University of Texas Health Science Center at San Antonio, South Texas Reference Laboratories, San Antonio, TX, USA Abstract: Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data

  17. Efficacy and safety of posaconazole in antifungal prophylaxis:a Meta-analysis%泊沙康唑预防性抗真菌疗效与安全性的Meta 分析

    Institute of Scientific and Technical Information of China (English)

    黄金柱; 罗晓; 李咏; 李欣; 王子绮; 佟春香; 赵振满; 卢来春

    2015-01-01

    显示试验组与氟康唑、伊曲康唑、伏立康唑和两性霉素 B 脂质体对照组比较,差异均无统计学意义(均 P >0.05),考虑可能存在发表偏倚。结论泊沙康唑预防侵袭性真菌感染的疗效优于非泊沙康唑类药物,安全性与非泊沙康唑类药物相似。%Objective To evaluate the effectiveness and safety of posaconazole in antifungal prophylaxis. Methods CNKI,VIP,CBM,Wangfang Database,PubMed,Cochrane Library,Embase, OVID,and Web of Science from the inception to March 2014 were searched. The randomized controlled trials(RCT)which compared posaconazole with placebo or other antifungal drugs in antifungal prophylaxis and the endpoint was the incidences of invasive fungal infection( IFI),all-cause mortality,or adverse reactions were collected. The related information was selected and RevMan 5. 1 software of Cochrane Collaboration was used for statistical analysis. The results were expressed as odds ratios( OR)and its corresponding 95% confidence intervals(CI). Results A total of 6 RCTs were enrolled into the study. Of them,4 RCTs were comparison of posaconazole with one other antifungal drug,and 2 RCTs were comparison of posaconazole with two kinds of other antifungal drugs. There were 1 410 cases in the experimental group and 929 cases in the control group. The results of Meta-analysis showed that the incidence of IFI in the experimental group was lower than that in the control group(OR = 0. 37,95% CI:0. 27-0. 50,P ﹤ 0. 000 01). The results of comparison of posaconazole with other antifungal drugs showed that the incidence of invasive fungal infections in the experimental group were lower than those in the fluconazol group(OR = 0. 42,95% CI:0. 28-0. 64,P ﹤ 0. 000 1)and the itraconazole group(OR = 0. 33, 95% CI:0. 21-0. 53,P ﹤ 0. 000 01). There were no statistical significant differences in incidence of invasive fungal infections between the experimental group and the control groups of voriconazole and

  18. Prevention of invasive fungal infections in immunocompromised patients: the role of delayed-release posaconazole

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    Soysal A

    2015-09-01

    Full Text Available Ahmet SoysalDivision of Pediatric Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Marmara University, Istanbul, TurkeyAbstract: Posaconazole is a triazole antifungal agent that has broad-spectrum activity against many yeasts and filamentous fungi, including Candida species, Cryptococcus neoformans, Aspergillus species, and Zygomycetes. This drug has been approved for the prevention of invasive fungal infections in patients with neutropenia and for the treatment of invasive fungal infections in hematopoietic stem cell transplant recipients with graft-versus-host disease. Studies on the clinical efficacy, safety, tolerability, and cost-effectiveness of posaconazole therapy were performed using the oral suspension form of the drug. Pharmacokinetic studies have found that the oral suspension form of posaconazole has problemeatic bioavailability: its absorption is affected by concomitant medication and food. This article discusses the pharmacokinetic properties of the newly developed posaconazole delayed-release tablet formulation and reviews the efficacy, safety, and cost-effectiveness of both the oral suspension and the new tablet formulation. In conclusion, the posaconazole tablet formulation has better systemic bioavailability, thereby enabling once-daily administration and better absorption in the presence of concomitant medication and food. However, well-designed clinical studies are needed to evaluate the use of the tablet formulation in real-life settings.Keywords: posaconazole delayed-release tablet, prophylaxis, invasive fungal infections

  19. The expenditures related to the use of antifungal drugs in patients with hematological cancers: a cost analysis

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    Gedik H

    2015-11-01

    Full Text Available Habip Gedik Department of Infectious Diseases and Clinical Microbiology, Ministry of Health Okmeydani Training and Research Hospital, Istanbul, Turkey Objective: The aim of this study is to analyze the expenditures related to the use of antifungal drugs in patients with hematological malignancies. Methods: In this retrospective study, the expenditures related to use of antifungal drugs for treatment of invasive fungal infections in patients with hematological malignancies between November 2010 and November 2012 were analyzed. Expenditures of antifungal drugs were calculated by converting the price billed to the Republic of Turkey Social Security Institution per patient using the US dollar ($ exchange rate. Results: We retrospectively analyzed the expenditures related to the use of antifungal drugs in 282 febrile episodes of 126 neutropenic patients. Voriconazole (VOR, caspofungin, and liposomal amphotericin B (L-AmB were administered as a first-line antifungal therapy to treat 72 febrile episodes of 65 neutropenic patients, 45 febrile episodes of 37 neutropenic patients, and 34 febrile episodes of 32 neutropenic patients, respectively. The expenditures related to the use of antifungal drugs per febrile neutropenic episode were $3,857.85 for VOR; $15,783.34 for caspofungin, and $21,561.02 for L-AmB, respectively. The expenditure related to the use of posaconazole (POS was $32,167.39 per patient for primary or secondary prophylaxis. Conclusion: Improving conditions in the patient's room, choosing pre-emptive antifungal treatment instead of empirical antifungal treatment, switching to tablet form of VOR after initiation of its intravenous form, secondary prophylaxis with VOR against invasive aspergillosis, primary prophylaxis with POS in high-risk patients, and choosing less L-AmB as being an alternative to other antifungal drugs, may reduce expenditures related to the use of antifungal drugs in the treatment of invasive fungal infections during

  20. 21 CFR 333.250 - Labeling of antifungal drug products.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of antifungal drug products. 333.250... Antifungal Drug Products § 333.250 Labeling of antifungal drug products. (a) Statement of identity. The... “antifungal.” (b) Indications. The labeling of the product states, under the heading “Indications,” the...

  1. Posaconazole: An Update of Its Clinical Use

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    Simon Leung

    2015-10-01

    Full Text Available Posaconazole (PCZ is a relatively new addition to the azole antifungals. It has fungicidal activities against Aspergillus fumigatus, Blastomyces dermatitidis, selected Candida species, Crytopcoccus neoformans, and Trichosporon. PCZ also has fungistatic activities against Candida, Coccidioides, selected Fusarium spp., Histoplasma, Scedosporium and Zygomycetes. In addition, combining the drug with caspofungin or amphotericin B results in a synergistic interaction against A. fumigatus, C. glabrata and C. neoformans. The absorption of PCZ suspension is enhanced when given with food, nutritional supplements, and carbonated beverages. Oral administration of PCZ in divided doses also increases its bioavailability. PCZ has a large volume of distribution and is highly protein bound (>95%. The main elimination route of PCZ is fecal. PCZ is an inhibitor of the CYP3A4 enzyme; therefore, monitoring for drug-drug interactions is warranted with other CYP3A4 substrates/inhibitors/inducers. The most common adverse effects include headache, fatigue, nausea, vomiting and elevated hepatic enzymes. PCZ, with its unique antifungal activities, expands the azole class of antifungal agents. Because of its limit in formulation, PCZ oral suspension is recommended in immunocompromised patients with functional gastrointestinaltracts who fail conventional antifungal therapies or who are suspected to have a breakthrough fungal infection. However, a delayed-release tablet formulation and intravenous (IV injection became available in 2014, expanding the use of PCZ in other patient populations, including individuals who are unable to take oral formulations.

  2. Antifungal drugs and resistance: Current concepts

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    Pramod Kumar Nigam

    2015-04-01

    Full Text Available Recently, clinical failure and relapses have been observed in patients treated with antifungals. Drug resistance has become an important problem leading to significant negative social, psychological, and occupational health effects and quality of life. Early recognition and treatment is essential to reduce morbidity and possibility of transmission. The increased use, inappropriate prescribing and over the counter sale of antifungal agents has also added in the development of resistance to these drugs. The main biochemical and molecular mechanisms that contribute to antifungal resistance include reduced uptake of the drug, an active transport out of the cell or modified drug metabolic degradation of the cell, changes in the interaction of the drug to the target site or other enzymes involved in the process by point mutations, overexpression of the target molecule, overproduction or mutation of the target enzyme, amplification and gene conversion (recombination, and increased cellular efflux and occurrence of biofilm. Although, there is considerable knowledge concerning the biochemical, genetic and clinical aspects of resistance to antifungal agents, expansion of our understanding of the mechanisms by which antifungal resistance emerges and spreads, quicker methods for the determination of resistance, targetting efflux pumps, especially ATP binding cassette (ABC transporters and heat shock protein 90, new drug delivery systems, optimizing therapy according to pharmacokinetic and pharmacodynamic characteristics, new classes of antifungal drugs that are active against azole-resistant isolates, and use of combinations of antifungal drugs or use of adjunctive immunostimulatory therapy and other modalities of treatment will clearly be important for future treatment strategies and in preventing development of resistance.

  3. Antifungal drugs and resistance: Current concepts

    OpenAIRE

    Pramod Kumar Nigam

    2015-01-01

    Recently, clinical failure and relapses have been observed in patients treated with antifungals. Drug resistance has become an important problem leading to significant negative social, psychological, and occupational health effects and quality of life. Early recognition and treatment is essential to reduce morbidity and possibility of transmission. The increased use, inappropriate prescribing and over the counter sale of antifungal agents has also added in the development of resistance to the...

  4. Antifungal drug discovery: the process and outcomes.

    Science.gov (United States)

    Calderone, Richard; Sun, Nuo; Gay-Andrieu, Francoise; Groutas, William; Weerawarna, Pathum; Prasad, Sridhar; Alex, Deepu; Li, Dongmei

    2014-01-01

    New data suggest that the global incidence of several types of fungal diseases have traditionally been under-documented. Of these, mortality caused by invasive fungal infections remains disturbingly high, equal to or exceeding deaths caused by drug-resistant tuberculosis and malaria. It is clear that basic research on new antifungal drugs, vaccines and diagnostic tools is needed. In this review, we focus upon antifungal drug discovery including in vitro assays, compound libraries and approaches to target identification. Genome mining has made it possible to identify fungal-specific targets; however, new compounds to these targets are apparently not in the antimicrobial pipeline. We suggest that 'repurposing' compounds (off patent) might be a more immediate starting point. Furthermore, we examine the dogma on antifungal discovery and suggest that a major thrust in technologies such as structural biology, homology modeling and virtual imaging is needed to drive discovery. PMID:25046525

  5. Mystery unraveled about antifungal drug targets

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ A long-standing mystery about the functional roles of the N-terminal region of protein N-myristoyltransferase, an ideal target for antifungal drugs, was recently decoded, thanks to the threeyear joint efforts of researchers from the CAS Key Laboratory of Molecular Biology and their US colleagues at the DuPont Stine Haskell Research Center.

  6. Antifungal effect of cumin essential oil alone and in combination with antifungal drugs

    OpenAIRE

    SAHADEO PATIL; PANKAJ MAKNIKAR; SUSHILKUMAR WANKHADE; CHANDRAKIRAN UKESH; MAHENDRA RA

    2015-01-01

    Abstract. Patil S, Maknikar P, Wankhade S, Ukesh C, Rai M. 2015. Antifungal effect of cumin essential oil alone and in combination with antifungal drugs. Nusantara Bioscience 7: 55-59. We report evaluation of antifungal activity of cumin seed oil and its pharmacological interactions when used in combination with some of the widely used conventional antifungal drugs using CLSI broth microdilution, agar disc diffusion and checkerboard microtitre assay against Candida. The essential oil was obta...

  7. Oral Antifungal Drugs in the Treatment of Dermatomycosis.

    Science.gov (United States)

    Tsunemi, Yuichiro

    2016-01-01

    Oral antifungal drugs are used primarily to treat tinea unguium; however, they are also useful for other types of tinea. For example, a combination of topical and oral antifungal drugs is effective in hyperkeratotic tinea pedis that is unresponsive to topical monotherapy. In cases of tinea facialis adjacent to the eyes, ears, or mouth, or widespread tinea corporis, or tinea cruris involving the complex skin folds of the external genitalia, it is difficult to apply topical drugs to all the lesions; therefore, oral antifungal drugs are necessary. Oral antifungal drugs are also useful not only for tinea but for widespread pityriasis versicolor and Malassezia folliculitis, candidal onychomycosis, and candidal paronychia and onychia. Topical antifungal drugs are in fact unsuitable for some mycoses. In tinea capitis, for example, irritation by topical drugs is likely to enhance inflammation; therefore, oral antifungal drug monotherapy is preferable. In interdigital tinea pedis with erosion or contact dermatitis, topical drugs are difficult to use because they tend to cause irritant dermatitis, resulting in exacerbation of the condition. In such cases, treatment should begin with a combination of topical corticosteroid therapy and oral antifungal drugs active against dermatophytes. Topical antifungal drugs are used after the complications resolve. A combination of topical and oral antifungal drugs can shorten the treatment period, thus improving patient adherence to topical treatment. Oral antifungal drugs are useful because of their wide range of applications in the treatment of dermatomycosis. PMID:27251319

  8. Tolerability and safety of antifungal drugs

    Directory of Open Access Journals (Sweden)

    Francesco Scaglione

    2013-08-01

    Full Text Available When treating critically ill patients, as those with fungal infections, attention should be focused on the appropriate use of drugs, especially in terms of dose, safety, and tolerability. The fungal infection itself and the concomitant physiological disorders concur to increase the risk of mortality in these patients, therefore the use of any antifungal agent should be carefully evaluated, considering both the direct action on the target fungus and the adverse effects eventually caused. Among antifungal drugs, echinocandins have the greatest tolerability. In fact, unlike amphotericin B, showing nephrotoxicity, and azoles, which are hepatotoxic, the use of echinocandins doesn’t result in major adverse events.http://dx.doi.org/10.7175/rhc.v4i2s.873

  9. Antifungal effect of cumin essential oil alone and in combination with antifungal drugs

    Directory of Open Access Journals (Sweden)

    SAHADEO PATIL

    2015-05-01

    Full Text Available Abstract. Patil S, Maknikar P, Wankhade S, Ukesh C, Rai M. 2015. Antifungal effect of cumin essential oil alone and in combination with antifungal drugs. Nusantara Bioscience 7: 55-59. We report evaluation of antifungal activity of cumin seed oil and its pharmacological interactions when used in combination with some of the widely used conventional antifungal drugs using CLSI broth microdilution, agar disc diffusion and checkerboard microtitre assay against Candida. The essential oil was obtained from cumin seeds using hydrodistillation technique and was later evaluated for the presence of major chemical constituents present in it using gas chromatography and mass spectrometry (GC-MS assay. The GC-MS assay revealed the abundance of γ-terpinene (35.42% followed by p-cymene (30.72%. The agar disc diffusion assay demonstrated highly potent antifungal effect against Candida species. Moreover, the combination of cumin essential oil (CEO with conventional antifungal drugs was found to reduce the individual MIC of antifungal drug suggesting the occurrence of synergistic interactions. Therefore, the therapy involving combinations of CEO and conventional antifungal drugs can be used for reducing the toxicity induced by antifungal drugs and at the same time enhancing their antifungal efficacy in controlling the infections caused due to Candida species.

  10. Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections.

    Science.gov (United States)

    Wiederhold, Nathan P

    2016-01-01

    Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data regarding clinical efficacy are needed. PMID:26730212

  11. Antifungal Drug Resistance - Concerns for Veterinarians

    Directory of Open Access Journals (Sweden)

    Bharat B. Bhanderi

    2009-10-01

    Full Text Available In the 1990s, there were increased incidences of fungal infectious diseases in human population which might be due to increase in immunosuppressive diseases. But the major concern was increase in prevalence of resistance to antifungal drugs which were reported both in the fungal isolates of human beings and that of animal origin. In both animals and human beings, resistance to antimicrobial agents has important implications for morbidity, mortality and health care costs, because resistant strains are responsible for bulk of infection in animals and human beings, and large number of antimicrobial classes offers more diverse range of resistance mechanisms to study and resistance determinants move into standard well-characterized strains that facilitates the detailed study of molecular mechanisms of resistance in microorganisms. Studies on resistance to antifungal agents has been lagging behind that of antibacterial resistance for several reasons, the foremost reason might be fungal agents were not recognized as important animal and human pathogens, until relatively in recent past. But the initial studies of antifungal drug resistance in the early 1980s, have accumulated a wealth of knowledge concerning the clinical, biochemical, and genetic aspects of this phenomenon. Presently, exploration of the molecular aspects for antifungal drug resistance has been undertaken. Recently, the focus was on several points like developing a more detailed understanding of the mechanisms of antimicrobial resistance, improved methods to detect resistance when it occurs, methods to prevent the emergence and spread of resistance and new antimicrobial options for the treatment of infections caused by resistant organisms. [Vet. World 2009; 2(5.000: 204-207

  12. Use of antifungal drugs in hematology

    Directory of Open Access Journals (Sweden)

    Marcio Nucci

    2012-01-01

    Full Text Available Invasive fungal disease represents a major complication in hematological patients. Antifungal agents are frequently used in hematologic patients for different purposes. In neutropenic patients, antifungal agents may be used as prophylaxis, as empiric or preemptive therapy, or to treat an invasive fungal disease that has been diagnosed. The hematologist must be familiar with the epidemiology, diagnostic tools and strategies of antifungal use, as well as the pharmacologic proprieties of the different antifungal agents. In this paper the principal antifungal agents used in hematologic patients will be discussed as will the clinical scenarios where these agents have been used.

  13. In vitro susceptibility testing of Aspergillus spp. against voriconazole, itraconazole, posaconazole, amphotericin B and caspofungin

    Institute of Scientific and Technical Information of China (English)

    SHI Jun-yan; WANG He; GUO Li-na; XU Ying-chun; SHI Yi; L(U) Huo-xiang; LIU Yong; ZHAO Wang-sheng; CHEN Dong-mei; XI Li-yan; ZHOU Xin

    2010-01-01

    Background During recent years, the incidence of serious infections caused by opportunistic fungi has increased dramatically due to alterations of the immune status of patients with hematological diseases, malignant tumors,transplantations and so forth. Unfortunately, the wide use of triazole antifungal agents to treat these infections has lead to the emergence of Aspergillus spp. resistant to triazoles. The present study was to assess the in vitro activities of five antifungal agents (voriconazole, itraconazole, posaconazole, amphotericin B and caspofungin) against different kinds of Aspergillus spp. that are commonly encountered in the clinical setting.Methods The agar-based Etest MIC method was employed. One hundred and seven strains of Aspergillus spp. (5 species) were collected and prepared according to Etest Technique Manuel. Etest MICs were determined with RPMI agar containing 2% glucose and were read after incubation for 48 hours at 35℃. MIC50, MIC90 and MIC range were acquired by Whonet 5.4 software.Results The MIC90 of caspofungin against A. fumigatus, A. flavus and A. nidulans was 0.094 μg/ml whereas the MIC90 against A. niger was 0.19 μg/ml. For these four species, the MlC90 of caspofungin was the lowest among the five antifungal agents. For A. terrus, the MIC90 of posaconazole was the lowest. For A. fumigatus and A. flavus, the MlC90in order of increasing was caspofungin, posaconazole, voriconazole, itraconazole, and amphotericin B. The MIC of amphotericin B against A. terrus was higher than 32 μg/ml in all 7 strains tested.Conclusions The in vitro antifungal susceptibility test shows the new drug caspofungin, which is a kind of echinocandins, has good activity against the five species of Aspergillus spp. and all the triazoles tested have better in vitro activity than traditional amphotericin B.

  14. Use of antifungal drugs in hematology

    OpenAIRE

    Marcio Nucci

    2012-01-01

    Invasive fungal disease represents a major complication in hematological patients. Antifungal agents are frequently used in hematologic patients for different purposes. In neutropenic patients, antifungal agents may be used as prophylaxis, as empiric or preemptive therapy, or to treat an invasive fungal disease that has been diagnosed. The hematologist must be familiar with the epidemiology, diagnostic tools and strategies of antifungal use, as well as the pharmacologic proprieties of the dif...

  15. Targeting efflux pumps to overcome antifungal drug resistance.

    Science.gov (United States)

    Holmes, Ann R; Cardno, Tony S; Strouse, J Jacob; Ivnitski-Steele, Irena; Keniya, Mikhail V; Lackovic, Kurt; Monk, Brian C; Sklar, Larry A; Cannon, Richard D

    2016-08-01

    Resistance to antifungal drugs is an increasingly significant clinical problem. The most common antifungal resistance encountered is efflux pump-mediated resistance of Candida species to azole drugs. One approach to overcome this resistance is to inhibit the pumps and chemosensitize resistant strains to azole drugs. Drug discovery targeting fungal efflux pumps could thus result in the development of azole-enhancing combination therapy. Heterologous expression of fungal efflux pumps in Saccharomyces cerevisiae provides a versatile system for screening for pump inhibitors. Fungal efflux pumps transport a range of xenobiotics including fluorescent compounds. This enables the use of fluorescence-based detection, as well as growth inhibition assays, in screens to discover compounds targeting efflux-mediated antifungal drug resistance. A variety of medium- and high-throughput screens have been used to identify a number of chemical entities that inhibit fungal efflux pumps. PMID:27463566

  16. Antifungal drug discovery through the study of invertebrate model hosts

    OpenAIRE

    Pukkila-Worley, R.; Holson, E.; Wagner, F.; Mylonakis, E.

    2009-01-01

    There is an urgent need for new antifungal agents that are both effective and non-toxic in the therapy of systemic mycoses. The model nematode Caenorhabditis elegans has been used both to elucidate evolutionarily conserved components of host-pathogen interactions and to screen large chemical libraries for novel antimicrobial compounds. Here we review the use of C. elegans models in drug discovery and discuss caffeic acid phenethyl ester, a novel antifungal agent identified using an in vivo sc...

  17. 泊沙康唑的药动和药效学评价%A Review of Posaconazole Pharmacokinetic and Pharmacodynamic Studies

    Institute of Scientific and Technical Information of China (English)

    梅丹; 梅隆; 刘梅; 刘正印

    2014-01-01

    Objective: To review the PK, PD, pharmacology, drug-drug interaction, safety and clinical application studies of posaconazole. Methods: Relevant information was identified through a literature search of Medline (1996-2013) and FDA website. Results: The oral absorption of Posaconazole is related with the dosage and significantly influenced by food. Multi-dose administration with Posaconazole wil improve the relative bioavailability. Posaconazole is mainly metabolized by UDP enzyme. The inducers and inhibitors of this enzyme wil affect the plasma concentration. Conclusion:Posaconazole is an extended -spectrum azole antifungal agents. The introduction of Posaconazole into China wil significantly expand both prophylaxis and treatment options for invasive fungal infections.%目的:综述介绍泊沙康唑的药动和药效学评价。方法:检索10余年来的相关文献,介绍其药学相关信息。结果:泊沙康唑的口服制剂吸收在一定范围内与剂量相关,且明显受食物摄入的影响,相对生物利用度与给药方案相关,分次服用有助于提高其生物利用度(BA),主要通过葡萄糖醛酸转移酶(UDP)酶代谢,该酶的诱导或抑制剂会影响药物的浓度。结论:泊沙康唑是近年来新的三唑类抗真菌药,充分了解药品的药理、药动和药效学信息,有助于临床合理选药、用药。

  18. Update on antifungal drug resistance mechanisms of Aspergillus fumigatus.

    Science.gov (United States)

    Chamilos, G; Kontoyiannis, D P

    2005-12-01

    Although the arsenal of agents with anti-Aspergillus activity has expanded over the last decade, mortality due to invasive aspergillosis (IA) remains unacceptably high. Aspergillus fumigatus still accounts for the majority of cases of IA; however less susceptible to antifungals non-fumigatus aspergilli began to emerge. Antifungal drug resistance of Aspergillus might partially account for treatment failures. Recent advances in our understanding of mechanisms of antifungal drug action in Aspergillus, along with the standardization of in vitro susceptibility testing methods, has brought resistance testing to the forefront of clinical mycology. In addition, molecular biology has started to shed light on the mechanisms of resistance of A. fumigatus to azoles and the echinocandins, while genome-based assays show promise for high-throughput screening for genotypic antifungal resistance. Several problems remain, however, in the study of this complex area. Large multicenter clinical studies--point prevalence or longitudinal--to capture the incidence and prevalence of antifungal resistance in A. fumigatus isolates are lacking. Correlation of in vitro susceptibility with clinical outcome and susceptibility breakpoints has not been established. In addition, the issue of cross-resistance between the newer triazoles is of concern. Furthermore, in vitro resistance testing for polyenes and echinocandins is difficult, and their mechanisms of resistance are largely unknown. This review examines challenges in the diagnosis, epidemiology, and mechanisms of antifungal drug resistance in A. fumigatus. PMID:16488654

  19. Solid lipid nanoparticles for antifungal drugs delivery for topical applications.

    Science.gov (United States)

    Trombino, Sonia; Mellace, Silvia; Cassano, Roberta

    2016-09-01

    Systemic and local infections caused by fungi, in particular those concerning the skin and nails, are increasing. Various drugs are used for mycoses treatment such as amphotericin B, nystatin and ketoconazole, fluconazole, itraconazole and fluconazole, among others. Unfortunately, many of these antifungal agents can cause side effects such as allergic and severe skin reaction. With the aim to reduce these side effects and maximize the antifungal drug activity, various drug-delivery systems have been formulated and been investigated in the last few years. In this context, solid lipid nanoparticles are attracting great attention. The aim of this review is to highlight the role of solid lipid nanoparticles as carriers of antifungal drugs for topical applications. PMID:27582235

  20. Antifungal susceptibility of Malassezia pachydermatis biofilm.

    Science.gov (United States)

    Figueredo, Luciana A; Cafarchia, Claudia; Otranto, Domenico

    2013-11-01

    Antifungal resistance has been associated with biofilm formation in many microorganisms, but not yet in Malassezia pachydermatis. This saprophytic yeast can cause otitis and dermatitis in dogs and has emerged as an important human pathogen, responsible for systemic infections in neonates in intensive care units. This study aims to evaluate the in vitro antifungal susceptibility of M. pachydermatis strains, in both their planktonic and sessile forms, to fluconazole, miconazole, ketoconazole, itraconazole, posaconazole, terbinafine and voriconazole using the XTT assay and Clinical and Laboratory Standards Institute (CLSI) microdilution method. The minimum inhibitory concentration (MIC) values recorded for each drug were significantly higher for sessile cells relative to planktonic cells to the extent that ≥ 90% of M. pachydermatis strains in their sessile form were classified as resistant to all antifungal agents tested. Data suggest that M. pachydermatis biofilm formation is associated with antifungal resistance, paving the way towards investigating drug resistance mechanisms in Malassezia spp. PMID:23834283

  1. Mechanisms of antifungal drug resistance in Candida dubliniensis.

    LENUS (Irish Health Repository)

    Coleman, David C

    2010-06-01

    Candida dubliniensis was first described in 1995 and is the most closely related species to the predominant human fungal pathogen Candida albicans. C. dubliniensis is significantly less prevalent and less pathogenic than C. albicans and is primarily associated with infections in HIV-infected individuals and other immunocompromised cohorts. The population structure of C. dubliniensis consists of three well-defined major clades and is significantly less diverse than C. albicans. The majority of C. dubliniensis isolates are susceptible to antifungal drugs commonly used to treat Candida infections. To date only two major patterns of antifungal drug resistance have been identified and the molecular mechanisms of these are very similar to the resistance mechanisms that have been described previously in C. albicans. However, significant differences are evident in the predominant antifungal drug mechanisms employed by C. dubliniensis, differences that reflect its more clonal nature, its lower prevalence and characteristics of its genome, the complete sequence of which has only recently been determined.

  2. Posaconazole: SCH 56592.

    Science.gov (United States)

    2003-01-01

    Posaconazole [SCH 56592, SPRIAFIL, Noxafil] is an orally active triazole derivative that is in phase III trials with the Schering-Plough Research Institute (SPRI) in the US for the treatment of serious opportunistic fungal infections, including aspergillosis, candidiasis, coccidioidomycosis and fusariosis. This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. Preclinical studies have also been conducted in Italy for the potential treatment of Cryptococcus neoformans infection (cryptococcosis).

  3. Successful Use of Posaconazole to Treat Invasive Cutaneous Fungal Infection in a Liver Transplant Patient on Sirolimus

    Directory of Open Access Journals (Sweden)

    Randah Dahlan

    2012-01-01

    Full Text Available Fungi are an important and common cause of cutaneous infections affecting solid organ transplant recipients. These infections can represent a primary site of infection with the potential for dissemination, or a manifestation of metastatic infection. The high morbidity and mortality associated with these infections necessitates urgent therapy with antifungal drugs; however, the interaction between these drugs and immunosuppressive therapies can be a major limitation because of drug toxicity. A case of soft tissue infection of the toe caused by Fusarium chlamydosporum and Candida guilliermondii in a liver transplant patient on sirolimus, who was successfully treated with the new antifungal agent posaconazole, is described. The pharmacokinetic interactions of sirolimus and the new triazoles, and their impact on treatment choices are briefly discussed.

  4. Posaconazole in the management of refractory invasive fungal infections

    Directory of Open Access Journals (Sweden)

    Stefan Langner

    2008-09-01

    Full Text Available Stefan Langner, Philipp B Staber, Peter NeumeisterDivision of Hematology, Department of Internal Medicine, Medical University of Graz, AustriaAbstract: The rising incidence of invasive fungal infections due to the expanding population of immunocompromised hosts and the increasing prevalence of fungal resistance has led to the need for novel antifungal agents. Posaconazole, a new member of the triazole class has demonstrated in vitro activity against a broad spectrum of fungi and clinical activity against various fungal pathogens, including Aspergillus spp., Candida spp., zygomycetes, and Fusarium spp. To date, posaconazole has been approved for prophylaxis of invasive fungal infections in stem cell transplant recipients with acute graft versus host disease (GVHD and neutropenic patients receiving intensive induction chemotherapy for acute myelogenous leukemia and myelodysplastic syndrome. In addition, it has been licensed for use in oropharyngeal candidiasis and for salvage therapy in invasive aspergillosis, fusariosis, coccidioidomycosis, chromoblastomycosis, and mycetoma. Posaconazole is the only azole with activity against zygomycetes and other difficult-to-treat fungi, representing a potential treatment option for refractory invasive mycosis. This article reviews available preclinical and clinical data of posaconazole, focusing on its role in the teatment of refractory invasive fungal infections.Keywords: posaconazole, refractory invasive fungal infections, salvage therapy

  5. Echinocandins: A ray of hope in antifungal drug therapy

    Directory of Open Access Journals (Sweden)

    Grover Neeta

    2010-01-01

    Full Text Available Invasive fungal infections are on the rise. Amphotericin B and azole antifungals have been the mainstay of antifungal therapy so far. The high incidence of infusion related toxicity and nephrotoxicity with amphotericin B and the emergence of fluconazole resistant strains of Candida glabrata egged on the search for alternatives. Echinocandins are a new class of antifungal drugs that act by inhibition of β (1, 3-D- glucan synthase, a key enzyme necessary for integrity of the fungal cell wall. Caspofungin was the first drug in this class to be approved. It is indicated for esophageal candidiasis, candidemia, invasive candidiasis, empirical therapy in febrile neutropenia and invasive aspergillosis. Response rates are comparable to those of amphotericin B and fluconazole. Micafungin is presently approved for esophageal candidiasis, for prophylaxis of candida infections in patients undergoing hematopoietic stem cell transplant (HSCT and in disseminated candidiasis and candidemia. The currently approved indications for anidulafungin are esophageal candidiasis, candidemia and invasive candidiasis. The incidence of infusion related adverse effects and nephrotoxicity is much lower than with amphotericin B. The main adverse effect is hepatotoxicity and derangement of serum transaminases. Liver function may need to be monitored. They are, however, safer in renal impairment. Even though a better pharmacoeconomical choice than amphotericin B, the higher cost of these drugs in comparison to azole antifungals is likely to limit their use to azole resistant cases of candidial infections and as salvage therapy in invasive aspergillosis rather than as first line drugs.

  6. Mode of Antifungal Drugs Interaction with Cytochrome P- 450

    Directory of Open Access Journals (Sweden)

    M- Mahmodian

    1991-07-01

    Full Text Available Computer was used to identify the interactions of substrates and antifungal drugs with the enzyme, Cytochrome P-450; and then Molplot.bas computer program was applied to get three dimensional figures of 5-hydroxy camphor.oxidation products of camphor analogues, and antifungal drugs.Cartesian characteristics of atoms building molecules, are taken from Buildz. for program, which can calculate X,Y,Z coordinates of atoms by Zmatrix data. The other program which can calculate X,Y,Z coordinates, using fractional characteristics, is the Coord, for program that, gives our cartesian characteristics of the atoms of molecule, then by using these data, we obtain three dimensional figures and distance between active atoms in compounds under consideration. Results show that distance between two oxygen atoms in 5-exo-hydroxy- camphor and the other compounds obtained from oxidation of camphor analogues, with the distance of two oxygen atoms in antifungal compounds under discussion are equal. Therefore, we can conclude that, the antifungal molecule also interacts with enzyme's active site, by its own sites, in a similar manner to the 5-hydroxy camphor molecule, which is:"n1. Nitrogen atom (N of Imidazole and Triazole ring in antifungal molecule with Iron atom in heam molecule belonging to Cytochrome P-450 enzyme, are coordinated."n2. The other atoms such as : 0,S or N in structure of the antifungal drug are coordinated with hydrogen atom of hydroxyl group belong ing to Tyr-96 in the structure of enzyme, forming hydrogen bonding.

  7. Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology

    OpenAIRE

    Ashbee, H. Ruth; Barnes, Rosemary A.; Johnson, Elizabeth M.; Richardson, Malcolm D.; Gorton, Rebecca; Hope, William W.

    2013-01-01

    The burden of human disease related to medically important fungal pathogens is substantial. An improved understanding of antifungal pharmacology and antifungal pharmacokinetics–pharmacodynamics has resulted in therapeutic drug monitoring (TDM) becoming a valuable adjunct to the routine administration of some antifungal agents. TDM may increase the probability of a successful outcome, prevent drug-related toxicity and potentially prevent the emergence of antifungal drug resistance. Much of the...

  8. Inhibitory Potential of Antifungal Drugs on ATP-Binding Cassette Transporters P-Glycoprotein, MRP1 to MRP5, BCRP, and BSEP.

    Science.gov (United States)

    Lempers, Vincent J C; van den Heuvel, Jeroen J M W; Russel, Frans G M; Aarnoutse, Rob E; Burger, David M; Brüggemann, Roger J; Koenderink, Jan B

    2016-06-01

    Inhibition of ABC transporters is a common mechanism underlying drug-drug interactions (DDIs). We determined the inhibitory potential of antifungal drugs currently used for invasive fungal infections on ABC transporters P-glycoprotein (P-gp), MRP1 to MRP5, BCRP, and BSEP in vitro Membrane vesicles isolated from transporter-overexpressing HEK 293 cells were used to investigate the inhibitory potential of antifungal drugs (250 μM) on transport of model substrates. Concentration-inhibition curves were determined if transport inhibition was >60%. Fifty percent inhibitory concentrations (IC50s) for P-gp and BCRP were both 2 μM for itraconazole, 5 and 12 μM for hydroxyitraconazole, 3 and 6 μM for posaconazole, and 3 and 11 μM for isavuconazole, respectively. BSEP was strongly inhibited by itraconazole and hydroxyitraconazole (3 and 17 μM, respectively). Fluconazole and voriconazole did not inhibit any transport for >60%. Micafungin uniquely inhibited all transporters, with strong inhibition of MRP4 (4 μM). Anidulafungin and caspofungin showed strong inhibition of BCRP (7 and 6 μM, respectively). Amphotericin B only weakly inhibited BCRP-mediated transport (127 μM). Despite their wide range of DDIs, azole antifungals exhibit selective inhibition on efflux transporters. Although echinocandins display low potential for clinically relevant DDIs, they demonstrate potent in vitro inhibitory activity. This suggests that inhibition of ABC transporters plays a crucial role in the inexplicable (non-cytochrome P450-mediated) DDIs with antifungal drugs. PMID:27001813

  9. Synthesis and investigation of novel benzimidazole derivatives as antifungal agents.

    Science.gov (United States)

    Chandrika, Nishad Thamban; Shrestha, Sanjib K; Ngo, Huy X; Garneau-Tsodikova, Sylvie

    2016-08-15

    The rise and emergence of resistance to antifungal drugs by diverse pathogenic fungal strains have resulted in an increase in demand for new antifungal agents. Various heterocyclic scaffolds with different mechanisms of action against fungi have been investigated in the past. Herein, we report the synthesis and antifungal activities of 18 alkylated mono-, bis-, and trisbenzimidazole derivatives, their toxicities against mammalian cells, as well as their ability to induce reactive oxygen species (ROS) in yeast cells. Many of our bisbenzimidazole compounds exhibited moderate to excellent antifungal activities against all tested fungal strains, with MIC values ranging from 15.6 to 0.975μg/mL. The fungal activity profiles of our bisbenzimidazoles were found to be dependent on alkyl chain length. Our most potent compounds were found to display equal or superior antifungal activity when compared to the currently used agents amphotericin B, fluconazole, itraconazole, posaconazole, and voriconazole against many of the strains tested. PMID:27301676

  10. Nationwide study of candidemia, antifungal use, and antifungal drug resistance in Iceland, 2000 to 2011.

    Science.gov (United States)

    Asmundsdottir, Lena Ros; Erlendsdottir, Helga; Gottfredsson, Magnus

    2013-03-01

    Candidemia is often a life-threatening infection, with highly variable incidence among countries. We conducted a nationwide study of candidemia in Iceland from 2000 to 2011, in order to determine recent trends in incidence rates, fungal species distribution, antifungal susceptibility patterns, and concurrent antifungal consumption. A total of 208 infection episodes in 199 patients were identified. The average incidence during the 12 years was 5.7 cases/100,000 population/year, which was significantly higher than that from 1990 to 1999 (4.3/100,000/year; P = 0.02). A significant reduction in the use of blood cultures was noted in the last 3 years of the study, coinciding with the economic crisis in the country (P 60 years, and varied by gender. Age-specific incidence among males >80 years old was 28.6/100,000/year, and it was 8.3/100,000/year for females in this age group (P = 0.028). The 30-day survival rate among adult patients remained unchanged compared to that from 1990 to 1999 (70.4% versus 69.5%, P = 0.97). Candida albicans was the predominant species (56%), followed by C. glabrata (16%) and C. tropicalis (13%). The species distribution remained stable compared to that from previous decades. Fluconazole use increased 2.4-fold from 2000 to 2011, with no increase in resistance. In summary, the incidence of candidemia in Iceland has continued to increase but may have reached a steady state, and no increase in antifungal drug resistance has been noted. Decreased use of blood cultures toward the end of the study may have influenced detection rates.

  11. SUSCEPTIBILITY OF CANDIDA SPECIES TO ANTIFUNGAL DRUGS IN WESTERN INDIA

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    Geeta M Vaghela

    2015-06-01

    Full Text Available Introduction: The increase in candidaemia is associated with high mortality. A shift has been observed in the relative frequency of each Candida spp. isolated from blood. Options of the antifungal drugs available for treatment of systemic and invasive candidiasis are restricted to polyenes, allylamines, azoles and recently developed echinocandin class of molecules. A rise in the incidence of antifungal resistance to Candida spp. has also been reported over the past decade. Studies on prevalence of infections and antifungal susceptibility testing are useful in deciding clinical strategies. Aims: To do species level identification and detect resistance, if any, among Indian clinical isolates of C. albicans. Methodology: From total 135 patients from a tertiary care hospital of Gujarat, Candida species were isolated from different clinical specimens. The growth of Candida on Sabouraud's dextrose agar was confirmed by Gram staining in which gram positive budding fungal cells were observed. Then its growth was examined for colony morphology on Sabouraud's dextrose agar and chlamydospore production on Corn meal tween 80 agar. Germ tube tests and other biochemical tests like sugar fermentation, sugar assimilation and urease test were performed to identify the species of Candida. Antifungal susceptibility testing was performed by NCCLS M44-A Disc diffusion method. Results: Out of total 135 samples, C. Albicans were isolated from 52 (38.5%. Among Non Albican Candid (NAC, Candida glabrata was 36 (26.7% followed by Candida tropicalis 25(18.5%. C. albicans was found resistant to Fluconazole, Itraconazole and Amphotericine B in 3.8%, 3.8% and 1.9% cases respectively. For NAC, resistance of Fluconazole, Itraconazole and Amphotericine B was found in 4.8%, 3.6% and 2.4% cases respectively. [Natl J Med Res 2015; 5(2.000: 122-126

  12. Antifungal activity of ibuprofen against aspergillus species and its interaction with common antifungal drugs

    Institute of Scientific and Technical Information of China (English)

    LI Li-juan; CHEN Wei; XU Hui; WAN Zhe; LI Ruo-yu; LIU Wei

    2010-01-01

    Background The incidence of invasive aspergillosis (IA) has increased in frequency in immunocompromised patients with a variety of diseases. The poor prognosis might be due to limited treatment option. This study aimed to evaluate antifungal activity of ibuprofen against clinical isolates of aspergillus species, as well as its interaction with azoles or with amphotericin B or with micafungin.Methods Antifungal activity of ibuprofen against 10 strains of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus terreus were tested with both disk diffusion assay and standard broth microdilution method. To determine whether ibuprofen combined with itraconazole, voriconazole, amphotericin B, or micafungin had interactive effects on aspergillus spp., we used both disk diffusion assay and Chequerboard method.Results As for disk diffusion method, ibuprofen produced a zone of growth inhibition with diameters of (20.1±3.9) mm at 48 hours of incubation. As for broth microdilution method, the minimal inhibitory concentration (MIC) ranges of ibuprofen against aspergillus spp. were 1000-2000 μg/ml, and the minimal fungicidal concentration (MFC) ranges of that was 2000-8000 μg/ml. For 2 of 5 isolates, when ibuprofen combined with itraconazole or voriconazole, the zones of growth inhibition were larger than those of the individual drug. The results of Chequerboard method showed that fractional inhibitory concentration index (FICI) ranges were 1.125-2.500.Conclusions Ibuprofen is active against aspergillus spp.. And ibuprofen does not affect the in vitro activity of itraconazole, voriconazole, amphotericin B or micafungin against aspergillus spp..

  13. Posaconazole: A New Agent for the Prevention and Management of Severe, Refractory or Invasive Fungal Infections

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    Andrea V Page

    2008-01-01

    Full Text Available Posaconazole is the newest antifungal agent to be approved for use in Canada. With excellent in vitro activity against a broad spectrum of yeasts and filamentous fungi, as well as having a well-tolerated oral formulation, posaconazole offers many potential advantages. Of particular interest are its seemingly lower potential for cross-resistance with other azoles and its activity (unique among oral antifungal agents against the zygomycetes. As the incidence of both common and uncommon fungal infections increases commensurate with the growing population of immunocompromised individuals, posaconazole may ultimately become an important therapeutic option. The present article reviews the in vitro and in vivo data describing its activity, and focuses on both the proven and the potential clinical applications of this new triazole agent.

  14. First case of Tritirachium oryzae as agent of onychomycosis and its susceptibility to antifungal drugs.

    Science.gov (United States)

    Naseri, Ali; Fata, Abdolmajid; Najafzadeh, Mohammad Javad

    2013-08-01

    The first case of Tritirachium oryzae isolated from an Iranian patient is reported. A 44-year-old woman with a lesion in her fingernail was examined for onychomycosis. Direct microscopic examination of the nail clippings revealed fungal filaments and inoculation of portions of the nail clippings on cultures media yielded T. oryzae after 8 days. The isolate was identified as Tritirachium spp. on the basis of gross morphological characteristics of the fungal colony and microscopic characterization of slide cultures. The diagnosis of T. oryzae was confirmed by PCR sequencing of the internal transcribed spacer domain of the rDNA gene. In vitro antifungal susceptibility test demonstrated that the fungus was susceptible to itraconazole and posaconazole. The patient was treated with oral itraconazole. PMID:23591624

  15. Antitrypanosomal Treatment with Benznidazole Is Superior to Posaconazole Regimens in Mouse Models of Chagas Disease.

    Science.gov (United States)

    Khare, Shilpi; Liu, Xianzhong; Stinson, Monique; Rivera, Ianne; Groessl, Todd; Tuntland, Tove; Yeh, Vince; Wen, Ben; Molteni, Valentina; Glynne, Richard; Supek, Frantisek

    2015-10-01

    Two CYP51 inhibitors, posaconazole and the ravuconazole prodrug E1224, were recently tested in clinical trials for efficacy in indeterminate Chagas disease. The results from these studies show that both drugs cleared parasites from the blood of infected patients at the end of the treatment but that parasitemia rebounded over the following months. In the current study, we sought to identify a dosing regimen of posaconazole that could permanently clear Trypanosoma cruzi from mice with experimental Chagas disease. Infected mice were treated with posaconazole or benznidazole, an established Chagas disease drug, and parasitological cure was defined as an absence of parasitemia recrudescence after immunosuppression. Twenty-day therapy with benznidazole (10 to 100 mg/kg of body weight/day) resulted in a dose-dependent increase in antiparasitic activity, and the 100-mg/kg regimen effected parasitological cure in all treated mice. In contrast, all mice remained infected after a 25-day treatment with posaconazole at all tested doses (10 to 100 mg/kg/day). Further extension of posaconazole therapy to 40 days resulted in only a marginal improvement of treatment outcome. We also observed similar differences in antiparasitic activity between benznidazole and posaconazole in acute T. cruzi heart infections. While benznidazole induced rapid, dose-dependent reductions in heart parasite burdens, the antiparasitic activity of posaconazole plateaued at low doses (3 to 10 mg/kg/day) despite increasing drug exposure in plasma. These observations are in good agreement with the outcomes of recent phase 2 trials with posaconazole and suggest that the efficacy models combined with the pharmacokinetic analysis employed here will be useful in predicting clinical outcomes of new drug candidates. PMID:26239982

  16. Antifungal prophylaxis in stem cell transplantation centers in Turkey

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    Hamdi Akan

    2011-12-01

    Full Text Available Objective: This study aimed to determine the current state of antifungal prophylaxis in Turkish stem cell transplantation (SCT centers. Materials and Methods: The were 38 active stem cell transplantation centers in Turkey, 28 of which were registered with the European Group for Blood and Marrow Transplantation (EBMT. Survey questionnaires were sent to the 28 EBMT centers in an effort to collect data on antifungal prophylaxis in different settings. In all, 24 of the centers completed the survey; 1 of the 24 centers was excluded from the study, as it was under construction at the time and was not performing transplantation.Results: In all, 15 (65% of the 23 centers were adult SCT centers, 7 (31% were pediatric SCT centers, and 1 center treated both adult and pediatric patients. All centers (23/23 performed both allogeneic and autologous transplants, 20 centers performed non-myeloablative transplants, 8 performed cord blood transplants, and 7 performed unrelated transplants. Primary antifungal prophylaxis was used at all 23 centers during allogeneic transplants, whereas 18 of the 23 centers used it during every autologous transplant and 2 of the 23 centers used it during autologous transplants on a per case basis. The most common drug used for prophylaxis was fluconazole (F (21/23, followed by itraconazole (I (3/23, amphotericin-B (2/23, and posaconazole (1/23. Among the 23 centers, 3 reported that for allogenic transplants they changed the antifungal prophylactic in cases of graft versus host disease (GVHD, and 12 of the 23 centers reported that they changed the antifungal prophylactic in case of nearby construction. All 23 centers performed secondary prophylaxis. Conclusion: Antifungal prophylaxis for hematopoetic SCT patients was the standard protocol in the 23 centers included in the study, usually with such azoles as F. The introduction of posaconazole in Turkey and the potential approval of voriconazole for antifungal prophylaxis will

  17. Gastrointestinal basidiobolomycosis treated with posaconazole

    OpenAIRE

    Rose, Stacey R.; Lindsley, Mark D.; Hurst, Steven F; Paddock, Christopher D.; Damodaran, Thara; BENNETT, John

    2012-01-01

    A 67 year-old Caucasian male from Arizona presented with indolent symptoms of intestinal obstruction and hydronephrosis, found at surgery to be caused by a mass involving the terminal ileum and cecum, extending into the posterior abdominal wall and obstructing the right ureter. Histopathology was diagnostic of basidiobolomycosis. PCR of tissue and sequencing identified the fungus as, Basidiobolus ranarum. During one year of posaconazole treatment, the residual mass shrank, hydronephrosis was ...

  18. Aspergillus nidulans galactofuranose biosynthesis affects antifungal drug sensitivity.

    Science.gov (United States)

    Alam, Md Kausar; El-Ganiny, Amira M; Afroz, Sharmin; Sanders, David A R; Liu, Juxin; Kaminskyj, Susan G W

    2012-12-01

    The cell wall is essential for fungal survival in natural environments. Many fungal wall carbohydrates are absent from humans, so they are a promising source of antifungal drug targets. Galactofuranose (Galf) is a sugar that decorates certain carbohydrates and lipids. It comprises about 5% of the Aspergillus fumigatus cell wall, and may play a role in systemic aspergillosis. We are studying Aspergillus wall formation in the tractable model system, A. nidulans. Previously we showed single-gene deletions of three sequential A. nidulans Galf biosynthesis proteins each caused similar hyphal morphogenesis defects and 500-fold reduced colony growth and sporulation. Here, we generated ugeA, ugmA and ugtA strains controlled by the alcA(p) or niiA(p) regulatable promoters. For repression and expression, alcA(p)-regulated strains were grown on complete medium with glucose or threonine, whereas niiA(p)-regulated strains were grown on minimal medium with ammonium or nitrate. Expression was assessed by qPCR and colony phenotype. The alcA(p) and niiA(p) strains produced similar effects: colonies resembling wild type for gene expression, and resembling deletion strains for gene repression. Galf immunolocalization using the L10 monoclonal antibody showed that ugmA deletion and repression phenotypes correlated with loss of hyphal wall Galf. None of the gene manipulations affected itraconazole sensitivity, as expected. Deletion of any of ugmA, ugeA, ugtA, their repression by alcA(p) or niiA(p), OR, ugmA overexpression by alcA(p), increased sensitivity to Caspofungin. Strains with alcA(p)-mediated overexpression of ugeA and ugtA had lower caspofungin sensitivity. Galf appears to play an important role in A. nidulans growth and vigor.

  19. Cyanobacteria, Lyngbya aestuarii and Aphanothece bullosa as antifungal and antileishmanial drug resources

    Institute of Scientific and Technical Information of China (English)

    Maheep Kumar; Manoj Kumar Tripathi; Akanksha Srivastava; Jalaj Kumar Gour; Rakesh Kumar Singh; Ragini Tilak; Ravi Kumar Asthana

    2013-01-01

    To investigate two cyanobacteria isolated from different origins i.e. Lyngbya aestuarii(L. aestuarii) from brackish water and Aphanothece bullosa (A. bullosa) from fresh water paddy fields for antifungal and antileishmanila activity taking Candida albicans and Leishmaniadonovain as targets. Methods: Biomass of L. aestuarii and A. bullosa were harvested after 40 and 60 d respectively and lyophilized twice in methanol (100%) and redissolved in methanol (5%) for bioassay. Antifungal bioassay was done by agar well diffusion method while antileishmanial, by counting cell numbers and flageller motility observation of promastigotes and amastigotes fromL. donovani . Fluconazole and 5% methanol were used as control. Results: Both the cyanobacteria were found to be potent source of antifungal activity keeping fluconazole as positive control, however, methanolic crude extract (15 mg/mL) of A. bullosa was found more potent (larger inhibition zone) over that of methanolic crude extract of L. aestuarii. Similarly antileishmanial activity of crude extract (24.0 mg/mL) of A. bullosa was superior over that of methanolic crude extract of L. aestuarii (25.6 mg/mL). Conclusions: Antifungal and antileishmanial drugs are still limited in the market. Screening of microbes possessing antifungal and antileishmanial activity drug is of prime importance. Cyanobacteria are little explored in this context because most of the drugs in human therapy are derived from microorganisms, mainly bacterial, fungal and actinomycetes. Thus in the present study two cyanobacterial strains from different origins showed potent source of antifungal and antileishmanial biomolecules.

  20. Network Meta-analysis and Pharmacoeconomic Evaluation of Fluconazole, Itraconazole, Posaconazole, and Voriconazole in Invasive Fungal Infection Prophylaxis.

    Science.gov (United States)

    Zhao, Ying Jiao; Khoo, Ai Leng; Tan, Gloria; Teng, Monica; Tee, Caroline; Tan, Ban Hock; Ong, Benjamin; Lim, Boon Peng; Chai, Louis Yi Ann

    2015-11-02

    Invasive fungal infections (IFIs) are associated with high mortality rates and large economic burdens. Triazole prophylaxis is used for at-risk patients with hematological malignancies or stem cell transplants. We evaluated both the efficacy and the cost-effectiveness of triazole prophylaxis. A network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating fluconazole, itraconazole capsule and solution, posaconazole, and voriconazole was conducted. The outcomes of interest included the incidences of IFIs and deaths. This was coupled with a cost-effectiveness analysis from patient perspective over a lifetime horizon. Probabilities of transitions between health states were derived from the NMA. Resource use and costs were obtained from the Singapore health care institution. Data on 5,505 participants in 21 RCTs were included. Other than itraconazole capsule, all triazole antifungals were effective in reducing IFIs. Posaconazole was better than fluconazole (odds ratio [OR], 0.35 [95% confidence interval [CI], 0.16 to 0.73]) and itraconazole capsule (OR, 0.25 [95% CI, 0.06 to 0.97]), but not voriconazole (OR, 1.31 [95% CI, 0.43 to 4.01]), in preventing IFIs. Posaconazole significantly reduced all-cause deaths, compared to placebo, fluconazole, and itraconazole solution (OR, 0.49 to 0.54 [95% CI, 0.28 to 0.88]). The incremental cost-effectiveness ratio for itraconazole solution was lower than that for posaconazole (Singapore dollars [SGD] 12,546 versus SGD 26,817 per IFI avoided and SGD 5,844 versus SGD 12,423 per LY saved) for transplant patients. For leukemia patients, itraconazole solution was the dominant strategy. Voriconazole was dominated by posaconazole. All triazole antifungals except itraconazole capsule were effective in preventing IFIs. Posaconazole was more efficacious in reducing IFIs and all-cause deaths than were fluconazole and itraconazole. Both itraconazole solution and posaconazole were cost-effective in the Singapore health care

  1. Synergy and antagonism between iron chelators and antifungal drugs in Cryptococcus.

    Science.gov (United States)

    Lai, Yu-Wen; Campbell, Leona T; Wilkins, Marc R; Pang, Chi Nam Ignatius; Chen, Sharon; Carter, Dee A

    2016-10-01

    Fungal infections remain very difficult to treat, and developing new antifungal drugs is difficult and expensive. Recent approaches therefore seek to augment existing antifungals with synergistic agents that can lower the therapeutic dose, increase efficacy and prevent resistance from developing. Iron limitation can inhibit microbial growth, and iron chelators have been employed to treat fungal infections. In this study, chequerboard testing was used to explore combinations of iron chelators with antifungal agents against pathogenic Cryptococcus spp. with the aim of determining how disruption to iron homeostasis affects antifungal susceptibility. The iron chelators ethylenediaminetetraacetic acid (EDTA), deferoxamine (DFO), deferiprone (DFP), deferasirox (DSX), ciclopirox olamine and lactoferrin (LF) were paired with the antifungal agents amphotericin B (AmB), fluconazole, itraconazole, voriconazole and caspofungin. All chelators except for DFO increased the efficacy of AmB, and significant synergy was seen between AmB and LF for all Cryptococcus strains. Addition of exogenous iron rescued cells from the antifungal effect of LF alone but could not prevent inhibition by AmB + LF, indicating that synergy was not due primarily to iron chelation but to other properties of LF that were potentiated in the presence of AmB. Significant synergy was not seen consistently for other antifungal-chelator combinations, and EDTA, DSX and DFP antagonised the activity of azole drugs in strains of Cryptococcus neoformans var. grubii. This study highlights the range of interactions that can be induced by chelators and indicates that most antifungal drugs are not enhanced by iron limitation in Cryptococcus. PMID:27474467

  2. Adverse events of modern antifungal drugs during treatment of invasive fungal infections

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    N. V. Dmitrieva

    2013-01-01

    Full Text Available Characteristics of adverse events of modern antimycotics by organ systems and comparative frequency between different medicines and their groups are presented. The examples of incompatibility of antifungal drugs with other pharmacological groups are discussed. Records of adverse events and drug compatibility will allow the practitioner to prevent and timely cure possible complications, should they arise.

  3. In Vitro and In Vivo Studies of the Antiparasitic Activity of Sterol 14α-Demethylase (CYP51) Inhibitor VNI against Drug-Resistant Strains of Trypanosoma cruzi

    OpenAIRE

    Soeiro, Maria de Nazaré Correia; de Souza, Elen Mello; da Silva, Cristiane França; Batista, Denise da Gama Jaen; Batista, Marcos Meuser; Pavão, Beatriz Philot; Araújo, Julianna Siciliano; Aiub, Claudia Alessandra Fortes; da Silva, Patrícia Bernardino; Lionel, Jessica; Britto, Constança; Kim, Kwangho; Sulikowski, Gary; Hargrove, Tatiana Y.; Waterman, Michael R.

    2013-01-01

    Chagas disease affects more than 10 million people worldwide, and yet, as it has historically been known as a disease of the poor, it remains highly neglected. Two currently available drugs exhibit severe toxicity and low effectiveness, especially in the chronic phase, while new drug discovery has been halted for years as a result of a lack of interest from pharmaceutical companies. Although attempts to repurpose the antifungal drugs posaconazole and ravuconazole (inhibitors of fungal sterol ...

  4. Effects of the association of antifungal drugs on the antimicrobial action of endodontic sealers

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    Paulo Henrique WECKWERTH

    2015-01-01

    Full Text Available This in vitro study aimed to determine the susceptibility of oral specimens and ATCC lineages of Candida albicans for five endodontic sealers, which were pure and associated with two antifungal drugs, and to analyze their effect on the physical properties. For this purpose, 30 lineages of C. albicans, collected from the oral cavity of patients assisted at the endodontics clinic of the Universidade Sagrado Coração, were analyzed. Yeasts susceptibility to the sealers was tested by diffusion on agar plates. Physical properties were evaluated according to the ADA specification no. 57. The pure versions of the Sealer 26, AH Plus, Endofill, Fillapex, and Sealapex demonstrated antifungal activity, with Endofill presenting the greatest inhibition zones. All cements, except for Endofill, had their antifungal actions enhanced by addition of ketoconazole and fluconazole (p < 0.05, and the AH Plus presented the best antifungal activity. The addition of antifungal drugs did not interfere with the setting time and flowability of the sealers. It was concluded that the addition of antifungals to endodontic sealers enhanced the antimicrobial action of most cements tested without altering their physical properties.

  5. Candida Infections: An Update on Host Immune Defenses and Anti-Fungal Drugs

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    Ning Gao

    2016-04-01

    Full Text Available Infections by fungal pathogens such as Candida albicans and non-albicans Candida species are becoming increasing prevalent in the human population. Such pathogens cause life-threatening diseases with high mortality, particularly in immunocompromised patients. Host defenses against fungal infections are provided by an exquisite interplay between innate and adaptive immune responses. However, effective anti-fungal agents for Candida infections are limited, and fungal drug resistance is a significant treatment challenge. In this review, we summarize the current understanding of host–fungal interactions, discuss the modes action of anti-fungal drugs, explore host defense mechanisms, and define the new challenges for treating Candida infections.

  6. High Intracellular Concentrations of Posaconazole Do Not Impact on Functional Capacities of Human Polymorphonuclear Neutrophils and Monocyte-Derived Macrophages In Vitro.

    Science.gov (United States)

    Farowski, Fedja; Cornely, Oliver A; Hartmann, Pia

    2016-06-01

    Posaconazole is a commonly used antifungal for the prophylaxis and treatment of invasive fungal infections. We previously demonstrated that the intracellular concentration of posaconazole in peripheral blood mononuclear cells (PBMCs) and polymorphonuclear neutrophils (PMNs) was greatly increased compared to the plasma concentration. As these professional phagocytes are crucial to combat fungal infections, we set out to investigate if and how, beneficial or deleterious, this high loading of intracellular posaconazole impacts the functional capacities of these cells. Here, we show that high intracellular concentrations of posaconazole do not significantly impact PMN and monocyte-derived macrophage function in vitro In particular, killing capacity and cytoskeletal features of PMN, such as migration, are not affected, indicating that these cells serve as vehicles for posaconazole to the site of infection. Moreover, since posaconazole as such slowed the germination of Aspergillus fumigatus conidia, infected neutrophils released less reactive oxygen species (ROS). Based on these findings, we propose that the delivery of posaconazole by neutrophils to the site of Aspergillus species infection warrants control of the pathogen and preservation of tissue integrity at the same time. PMID:27021317

  7. Caenorhabditis elegans-based Model Systems for Antifungal Drug Discovery

    OpenAIRE

    Cleo G Anastassopoulou; Fuchs, Beth Burgwyn; Mylonakis, Eleftherios

    2011-01-01

    The substantial morbidity and mortality associated with invasive fungal infections constitute undisputed tokens of their severity. The continued expansion of susceptible population groups (such as immunocompromised individuals, patients undergoing extensive surgery, and those hospitalized with serious underlying diseases especially in the intensive care unit) and the limitations of current antifungal agents due to toxicity issues or to the development of resistance, mandate the development of...

  8. Sensitization of Candida albicans biofilms to various antifungal drugs by cyclosporine A

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    Shinde Ravikumar B

    2012-10-01

    Full Text Available Abstract Background Biofilms formed by Candida albicans are resistant towards most of the available antifungal drugs. Therefore, infections associated with Candida biofilms are considered as a threat to immunocompromised patients. Combinatorial drug therapy may be a good strategy to combat C. albicans biofilms. Methods Combinations of five antifungal drugs- fluconazole (FLC, voriconazole (VOR, caspofungin (CSP, amphotericin B (AmB and nystatin (NYT with cyclosporine A (CSA were tested in vitro against planktonic and biofilm growth of C. albicans. Standard broth micro dilution method was used to study planktonic growth, while biofilms were studied in an in vitro biofilm model. A chequerboard format was used to determine fractional inhibitory concentration indices (FICI of combination effects. Biofilm growth was analyzed using XTT-metabolic assay. Results MICs of various antifungal drugs for planktonic growth of C. albicans were lowered in combination with CSA by 2 to 16 fold. Activity against biofilm development with FIC indices of 0.26, 0.28, 0.31 and 0.25 indicated synergistic interactions between FLC-CSA, VOR-CSA, CSP-CSA and AmB-CSA, respectively. Increase in efficacy of the drugs FLC, VOR and CSP against mature biofilms after addition of 62.5 μg/ml of CSA was evident with FIC indices 0.06, 0.14 and 0.37, respectively. Conclusions The combinations with CSA resulted in increased susceptibility of biofilms to antifungal drugs. Combination of antifungal drugs with CSA would be an effective prophylactic and therapeutic strategy against biofilm associated C. albicans infections.

  9. Enhanced activity of antifungal drugs using natural phenolics against yeast strains of Candida and Cryptococcus

    Science.gov (United States)

    Candidiasis and cryptococcosis are diseases of widening global incidence as a result of increasing immunosuppressive disorders, such as AIDS. An enduring problem for treatment of these mycoses is recurrent development of resistance to introduced antifungal drugs. We examined the potential for enhan...

  10. Grafting β-Cyclodextrins to Silicone, Formulation of Emulsions and Encapsulation of Antifungal Drug

    Science.gov (United States)

    Noomen, Ahlem; Penciu, Alexandra; Hbaieb, Souhaira; Parrot-Lopez, Hélène; Amdouni, Noureddine; Chevalier, Yves; Kalfat, Rafik

    Emulsions of silicone polymers having β-cyclodextrin units as lateral chains have been prepared and used for the encapsulation of the antifungal drug griseofulvin. Such technology enables the formulation of active substances that are not soluble in water as dosage forms for topical administration.

  11. A Genomewide Screen in Schizosaccharomyces pombe for Genes Affecting the Sensitivity of Antifungal Drugs That Target Ergosterol Biosynthesis

    OpenAIRE

    Fang, Yue; Hu, Lingling; Zhou, Xin; Jaiseng, Wurentuya; Zhang, Ben; Takami, Tomonori; Kuno, Takayoshi

    2012-01-01

    We performed a genomewide screen for altered sensitivity to antifungal drugs, including clotrimazole and terbinafine, that target ergosterol biosynthesis using a Schizosaccharomyces pombe gene deletion library consisting of 3,004 nonessential haploid deletion mutants. We identified 109 mutants that were hypersensitive and 11 mutants that were resistant to these antifungals. Proteins whose absence rendered cells sensitive to these antifungals were classified into various functional categories,...

  12. Effectiveness of increasing the frequency of posaconazole syrup administration to achieve optimal plasma concentrations in patients with haematological malignancy.

    Science.gov (United States)

    Park, Wan Beom; Cho, Joo-Youn; Park, Sang-In; Kim, Eun Jung; Yoon, Seonghae; Yoon, Seo Hyun; Lee, Jeong-Ok; Koh, Youngil; Song, Kyoung-Ho; Choe, Pyoeng Gyun; Yu, Kyung-Sang; Kim, Eu Suk; Bang, Su Mi; Kim, Nam Joong; Kim, Inho; Oh, Myoung-Don; Kim, Hong Bin; Song, Sang Hoon

    2016-07-01

    Few data are available on whether adjusting the dose of posaconazole syrup is effective in patients receiving anti-cancer chemotherapy. The aim of this prospective study was to analyse the impact of increasing the frequency of posaconazole administration on optimal plasma concentrations in adult patients with haematological malignancy. A total of 133 adult patients receiving chemotherapy for acute myeloid leukaemia or myelodysplastic syndrome who received posaconazole syrup 200 mg three times daily for fungal prophylaxis were enrolled in this study. Drug trough levels were measured by liquid chromatography-tandem mass spectrometry. In 20.2% of patients (23/114) the steady-state concentration of posaconazole was suboptimal (syrup is effective for achieving optimal levels in patients with haematological malignancy undergoing chemotherapy. PMID:27234674

  13. Type I methionine aminopeptidase from Saccharomyces cerevisiae is a potential target for antifungal drug screening

    Institute of Scientific and Technical Information of China (English)

    Ling-ling CHEN; Jia LI; Jing-ya LI; Qun-li LUO; Wei-feng MAO; Qiang SHEN; Fa-jun NAN; Qi-zhuang YE

    2004-01-01

    AIM: To screen antifungal drug candidates using in vitro and in vivo assays based on type I methionine aminopeptidase from Saccharomyces cerevisiae (ScMetAP1). METHODS: A colorimetric assay suitable for high throughput screening (HTS) using recombinant ScMetAP1 protein expressed in Escherichia coli was established for antifungal lead discovery. A series of pyridine-2-carboxylic acid derivatives were characterized and a chemical library of 12 800 pure organic compounds was screened with the in vitro ScMetAP1 assay. Active compounds from the in vitro assay were further evaluated by a growth inhibition assay on yeast strain with deletion of ScMetAP1 gene mapl in comparison with the wild-type yeast strain and the yeast strain with deletion of type II enzyme (ScMetAP2)gene map2. RESULTS: Active ScMetAP1 inhibitors were identified from HTS. Some of the pyridine-2-carboxylic acid derivatives (compound 2 and 3) had selective inhibition of the growth of map2 deletion yeast and weak inhibition on wild-type yeast growth, while no inhibition on mapl deletion yeast. CONCLUSION: ScMetAP1 is a novel potential target for developing antifungal drugs. The in vitro and in vivo ScMetAP1 assays can serve as tools in discovering antifungal drug candidates.

  14. Characterisation of the Candida albicans Phosphopantetheinyl Transferase Ppt2 as a Potential Antifungal Drug Target.

    Directory of Open Access Journals (Sweden)

    Katharine S Dobb

    Full Text Available Antifungal drugs acting via new mechanisms of action are urgently needed to combat the increasing numbers of severe fungal infections caused by pathogens such as Candida albicans. The phosphopantetheinyl transferase of Aspergillus fumigatus, encoded by the essential gene pptB, has previously been identified as a potential antifungal target. This study investigated the function of its orthologue in C. albicans, PPT2/C1_09480W by placing one allele under the control of the regulatable MET3 promoter, and deleting the remaining allele. The phenotypes of this conditional null mutant showed that, as in A. fumigatus, the gene PPT2 is essential for growth in C. albicans, thus fulfilling one aspect of an efficient antifungal target. The catalytic activity of Ppt2 as a phosphopantetheinyl transferase and the acyl carrier protein Acp1 as a substrate were demonstrated in a fluorescence transfer assay, using recombinant Ppt2 and Acp1 produced and purified from E.coli. A fluorescence polarisation assay amenable to high-throughput screening was also developed. Therefore we have identified Ppt2 as a broad-spectrum novel antifungal target and developed tools to identify inhibitors as potentially new antifungal compounds.

  15. Paradoxical response preceding control of Scedosporium apiospermum mycetoma with posaconazole treatment.

    Science.gov (United States)

    Béraud, Guillaume; Desbois, Nicole; Coyo, Caroline; Quist, Danièle; Rozé, Benoit; Savorit, Luc; Cabié, André

    2015-01-01

    Mycetoma is a chronic granulomatous infection that is difficult to treat, notably when due to fungi such as Scedosporium apiospermum. Recent antifungal agents could be an option, but cases are rarely reported, and none with posaconazole. Paradoxical responses, defined as initial clinical worsening despite appropriate treatment, are common in tuberculosis but rare in deep mycoses in non-immunocompromised hosts. Hence, paradoxical responses in context other than mycobacterial infection in an immunocompromised host could provide insights into the pathophysiology and the optimal strategy for treatment. We report the first case of a mycetoma caused by S. apiospermum with bone involvement treated with posaconazole, and the paradoxical response observed at the beginning of the treatment. As with mycobacterial infections, a paradoxical response in deep mycosis could represent the earliest marker of therapeutic efficacy. PMID:26114987

  16. Ergosterol biosynthesis in Aspergillus fumigatus: its relevance as an antifungal target and role in antifungal drug resistance

    OpenAIRE

    Alcazar-Fuoli, Laura; Mellado, Emilia

    2013-01-01

    Ergosterol, the major sterol of fungal membranes, is essential for developmental growth and the main target of antifungals that are currently used to treat fatal fungal infections. Emergence of resistance to existing antifungals is a current problem and several secondary resistance mechanisms have been described in Aspergillus fumigatus clinical isolates. A full understanding of ergosterol biosynthetic control therefore appears to be essential for improvement of antifungal efficacy and to pre...

  17. Calcium signaling mediates antifungal activity of triazole drugs in the Aspergilli.

    Science.gov (United States)

    Liu, Fei-fei; Pu, Li; Zheng, Qing-qing; Zhang, Yuan-wei; Gao, Rong-sui; Xu, Xu-shi; Zhang, Shi-zhu; Lu, Ling

    2015-08-01

    Azoles are widely applied and largely effective as antifungals; however, the increasing prevalence of clinically resistant isolates has yet to be matched by approaches to improve the efficacy of antimicrobial therapy. In this study, using the model fungus Aspergillus nidulans and one of the most common human pathogen Aspergillus fumigatus as research materials, we present the evidence that calcium signaling is involved in the azole-antifungals-induced stress-response reactions. In normal media, antifungal-itraconazole (ITZ) is able to induce the [Ca(2+)]c increased sharply but the addition of calcium chelator-EGTA or BAPTA almost blocks the calcium influx responses, resulted in the dramatically decreasing of [Ca(2+)]c transient. Real-time PCR analysis verified that six-tested Ca(2+)-inducible genes-two calcium channels (cchA/midA), a calmodulin-dependent phosphatase-calcineurin (cnaA), a transcription factor-crzA, and two calcium transporters (pmrA/pmcA)-could be transiently up-regulated by adding ITZ, indicating these components are involved in the azole stress-response reaction. Defect of cnaA or crzA caused more susceptibility to azole antifungals than did single mutants or double deletions of midA and cchA. Notably, EGTA may influence Rh123 accumulation as an azole-mimicking substrate through the process of the drug absorption. In vivo studies of a Galleria mellonella model identified that the calcium chelator works as an adjunct antifungal agent with azoles for invasive aspergillosis. Most importantly, combination of ITZ and EGTA or ITZ with calcium signaling inhibitor-FK506 greatly enhances the ITZ efficacy. Thus, our study provides potential clues that specific inhibitors of calcium signaling could be clinically useful adjuncts to conventional azole antifungals in the Aspergilli.

  18. The expenditures related to the use of antifungal drugs in patients with hematological cancers: a cost analysis

    OpenAIRE

    Gedik H

    2015-01-01

    Habip Gedik Department of Infectious Diseases and Clinical Microbiology, Ministry of Health Okmeydani Training and Research Hospital, Istanbul, Turkey Objective: The aim of this study is to analyze the expenditures related to the use of antifungal drugs in patients with hematological malignancies. Methods: In this retrospective study, the expenditures related to use of antifungal drugs for treatment of invasive fungal infections in patients with hematological malignancies between November 20...

  19. In vitro antifungal susceptibility of Malassezia pachydermatis from dogs with and without skin lesions.

    Science.gov (United States)

    Cafarchia, Claudia; Figueredo, Luciana A; Iatta, Roberta; Montagna, Maria Teresa; Otranto, Domenico

    2012-03-23

    Canine Malassezia dermatitis is frequently treated with systemic ketoconazole (KTZ) and itraconazole (ITZ). However, no information is available on the antifungal susceptibility to azoles and allilamine of Malassezia pachydermatis isolates from dogs with or without skin lesions. The present study was designed to evaluate the in vitro antifungal susceptibility of M. pachydermatis strains from dogs with or without skin lesions to KTZ, ITZ, miconazole (MICO), fluconazole (FLZ), posaconazole (POS), voriconazole (VOR) and terbinafine (TER) using the Clinical and Laboratory Standards Institute reference Broth Microdilution Method (CLSI M27-A2). The association between the susceptibility to antifungal compounds and the origin of M. pachydermatis, from skin with or without lesions has been also assessed. A total of 62 M. pachydermatis strains from healthy dogs (i.e., Group A=30) or with skin lesions (i.e., Group B=32) were tested. ITZ, KTZ and POS showed the highest activity against M. pachydermatis strains, whereas MICO TER and FLZ the lowest. A higher number of Malassezia resistant strains were registered among isolates from Group B than those from Group A. This study indicates that M. pachydermatis strains were susceptible to ITZ, KTZ, and POS. However, dogs with lesions may harbour strains with low susceptibility to antifungal agents and displaying cross-resistance phenomena to azole. The antifungal therapy in Malassezia infections requires careful appraisal of choice of drugs especially in cases of unresponsiveness to antifungal treatment or recurrent infections. PMID:21962411

  20. Analysis toward innovative herbal antibacterial and antifungal drugs.

    Science.gov (United States)

    Dhankhar, Sandeep; Dhankhar, Seema; Kumar, Manish; Ruhil, Sonam; Balhara, Meenakshi; Chhillar, Anil K

    2012-12-01

    The antimicrobial activities of four medicinal plants Argemona mexicana, Achyranthes aspera, Catharanthus roseus, and Syzygium cumini were evaluated against Escherichia coli, Vibrio cholerae, Klebsiella pneumoniae, Proteus vulgaris, Bacillus subtilis, Salmonella typhi and three Aspergillus species. Extracts from Achyranthes aspera and Catharanthus roseus showed the highest antimicrobial potential (MIC 0.375-0.750 mg/ml) while extract from Argemona mexicana and Syzygium cumini, showed less activity. In disc diffusion assay, only eight out of twenty extracts showed antimicrobial activity at a concentration of 25.0 μg/ disc. The GCMS investigation reveals the existence of 2-bornanone; 1, 2-benzenedicarboxylic acid, bis (2-methylpropyl) ester; hexadecanoic acid, methyl ester and hexatriacontane in water extract fraction of C. roseus. The present research article provides a review of some medicinal plants incorporating antimicrobial drugs, together with recent advances in emerging therapeutics in clinical development and related patents for exploitation of herbal medicine. PMID:23072646

  1. Multifactorial analysis of effects of interactions among antifungal and antineoplastic drugs on inhibition of Candida albicans growth.

    OpenAIRE

    Ghannoum, M. A.; Motawy, M S; Abu Hatab, M A; Ibrahim, A.S.; Criddle, R. S.

    1989-01-01

    Interactions among antineoplastic and antifungal drugs affecting the inhibition of Candida albicans growth are complex functions of the nature of the drugs used in combination, their absolute concentrations, and also their relative concentrations. Studies of drug interactions involving the use of test drugs in fixed concentration ratios can lead to inaccurate conclusions about synergism or antagonism among the drugs. A multifactorial experimental design procedure in which the concentrations o...

  2. Biodirected synthesis of Miconazole-conjugated bacterial silver nanoparticles and their application as antifungal agents and drug delivery vehicles.

    Science.gov (United States)

    Kumar, C Ganesh; Poornachandra, Y

    2015-01-01

    The recent strategy to improve the efficacy of drugs is to combine them with metal nanoparticles for the control of microbial infections. Considering this fact, we developed a low cost and eco-friendly method for silver nanoparticles synthesis using the cell free supernatant of Delftia sp. strain KCM-006 and their application as antifungal agents and as a drug carrier. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis revealed the formation of spherical and monodispersed silver nanoparticles with an average size of 9.8 nm. The synthesized nanoparticles were found to be photoluminescent, highly stable and crystalline in nature having a zeta potential of -31 mV. The silver nanoparticles exhibited very good antifungal activity against various pathogenic Candida strains. Furthermore, the efficacy of nanoparticles was increased by conjugating the antifungal drug Miconazole to silver nanoparticles which exhibited significant fungicidal activity, inhibition of ergosterol biosynthesis and biofilm inhibition by increasing ROS levels. In addition, the cell viability and immunocytochemistry analysis against different normal cell lines including Chinese hamster ovary cells (CHO), human lung cell line (MRC5) and human vascular endothelial cells (HUVEC) demonstrated that these nanoparticles were non-toxic up to a concentration of 20 μM. In conclusion, these results suggest that the synthesized nanoparticles find application as both antifungal agents and drug delivery vehicles. This is a first report on the preparation of silver nanoparticles using culture supernatant from Delftia sp. and also on the conjugation of Miconazole, an antifungal drug, to the bacterial silver nanoparticles.

  3. Measurement and correlation of antifungal drugs solubility in pure supercritical CO2 using semiempirical models

    International Nuclear Information System (INIS)

    Highlights: → Ketoconazole (KZ) and clotrimazole (CZ) are two antifungal drugs. → The solubilities of KZ and CZ were measured in supercritical CO2. → The experimental results were correlated using five density based models. → The heats' of drug-CO2 solvation and drug vaporization were estimated. - Abstract: In the present study the solubilities of two antifungal drugs of ketoconazole and clotrimazole in supercritical carbon dioxide were measured using a simple static method. The experimental data were measured at (308 to 348) K, over the pressure range of (12.2 to 35.5) MPa. The mole fraction solubilities ranged from 0.2 . 10-6 to 17.45 . 10-5. In this study five density based models were used to calculate the solubility of drugs in supercritical carbon dioxide. The density based models are Chrastil, modified Chrastil, Bartle, modified Bartle and Mendez-Santiago and Teja (M-T). Interaction parameters for the studied models were obtained and the percentage of average absolute relative deviation (AARD%) in each calculation was displayed. The correlation results showed good agreement with the experimental data. A comparison among the five models revealed that the Bartle and its modified models gave much better correlations of the solubility data with an average absolute relative deviation (AARD%) ranging from 4.8% to 6.2% and from 4.5% to 6.3% for ketoconazole and clotrimazole, respectively. Using the correlation results, the heat of drug-CO2 solvation and that of drug vaporization was separately approximated in the range of (-22.1 to -26.4 and 88.3 to 125.9) kJ . mol-1.

  4. Ethosomes: a novel delivery system for antifungal drugs in the treatment of topical fungal diseases.

    Science.gov (United States)

    Bhalaria, M K; Naik, Sachin; Misra, A N

    2009-05-01

    Aim of this work was to prepare and characterize fluconazole (FLZ) encapsulated ethosomes, incorporate it in suitable dermatological base, and asses its comparative clinical efficacy in the treatment of Candidiasis patients against liposomal gel, marketed product and hydroethanolic solution of the drug. Drug encapsulated ethosomes and liposomes were prepared and optimized by "Hot" method technique and lipid film hydration technique. Vesicular carriers were characterized for % entrapment efficiency, particle size and shape, in vitro drug diffusion study, mean % reduction in dimension of Candidiasis lesion and stability study by using suitable analytical technique. Vesicle size and drug entrapment efficiency of the optimized ethosomes and liposomes were found to be 144 +/- 6.8 nm and 82.68% and 216 +/- 9.2 nm and 68.22% respectively. Microscopic examinations suggest ethosomes to be multilamellar spherical vesicles with a smooth surface. The differential scanning calorimetry results suggest high fluidity of the ethosomes than liposomes. In vitro drug diffusion studies demonstrated that % drug diffused from ethosomes was nearly twice than liposomes and three times higher than the hydroethanolic solution across rat skin. From the clinical evaluation, the developed novel delivery system demonstrated enhanced antifungal activity compared to liposomal formulation, marketed formulation and hydroethanolic solution of the drug.

  5. Ethosomes: a novel delivery system for antifungal drugs in the treatment of topical fungal diseases.

    Science.gov (United States)

    Bhalaria, M K; Naik, Sachin; Misra, A N

    2009-05-01

    Aim of this work was to prepare and characterize fluconazole (FLZ) encapsulated ethosomes, incorporate it in suitable dermatological base, and asses its comparative clinical efficacy in the treatment of Candidiasis patients against liposomal gel, marketed product and hydroethanolic solution of the drug. Drug encapsulated ethosomes and liposomes were prepared and optimized by "Hot" method technique and lipid film hydration technique. Vesicular carriers were characterized for % entrapment efficiency, particle size and shape, in vitro drug diffusion study, mean % reduction in dimension of Candidiasis lesion and stability study by using suitable analytical technique. Vesicle size and drug entrapment efficiency of the optimized ethosomes and liposomes were found to be 144 +/- 6.8 nm and 82.68% and 216 +/- 9.2 nm and 68.22% respectively. Microscopic examinations suggest ethosomes to be multilamellar spherical vesicles with a smooth surface. The differential scanning calorimetry results suggest high fluidity of the ethosomes than liposomes. In vitro drug diffusion studies demonstrated that % drug diffused from ethosomes was nearly twice than liposomes and three times higher than the hydroethanolic solution across rat skin. From the clinical evaluation, the developed novel delivery system demonstrated enhanced antifungal activity compared to liposomal formulation, marketed formulation and hydroethanolic solution of the drug. PMID:19579803

  6. Environmental isolation, biochemical identification, and antifungal drug susceptibility of Cryptococcus species

    Directory of Open Access Journals (Sweden)

    Valter Luis Iost Teodoro

    2013-12-01

    Full Text Available Introduction The incidence of opportunistic fungal infections has increased in recent years and is considered an important public health problem. Among systemic and opportunistic mycoses, cryptococcosis is distinguished by its clinical importance due to the increased risk of infection in individuals infected by human immunodeficiency virus. Methods To determine the occurrence of pathogenic Cryptococcus in pigeon excrement in the City of Araraquara, samples were collected from nine environments, including state and municipal schools, abandoned buildings, parks, and a hospital. The isolates were identified using classical tests, and susceptibility testing for the antifungal drugs (fluconazole, itraconazole, voriconazole, and amphotericin B independently was also performed. After collection, the excrement samples were plated on Niger agar and incubated at room temperature. Results A total of 87 bird dropping samples were collected, and 66.6% were positive for the genus Cryptococcus. The following species were identified: Cryptococcus neoformans (17.2%, Cryptococcus gattii (5.2%, Cryptococcus ater (3.5%, Cryptococcus laurentti (1.7%, and Cryptococcus luteolus (1.7%. A total of 70.7% of the isolates were not identified to the species level and are referred to as Cryptococcus spp. throughout the manuscript. Conclusions Although none of the isolates demonstrated resistance to antifungal drugs, the identification of infested areas, the proper control of birds, and the disinfection of these environments are essential for the epidemiological control of cryptococcosis.

  7. Usefulness of Defined Daily Dose and Days of Therapy in Pediatrics and Obstetrics-Gynecology: A Comparative Analysis of Antifungal Drugs (2000–2001, 2005–2006, and 2010–2011)

    OpenAIRE

    Guillot, Justine; Lebel, Denis; Roy, Hélène; Ovetchkine, Philippe; Bussières, Jean-François

    2014-01-01

    OBJECTIVES: The objective was to describe antifungal drug use by using the number of defined daily doses (DDD)/1000 patient-days per antifungal, the number of days of therapy (DOT)/1000 patient-days per antifungal, and the mean dose in mg/kg/day per antifungal during a 10-year period.

  8. Hollow polycaprolactone composite fibers for controlled magnetic responsive antifungal drug release.

    Science.gov (United States)

    Wang, Baolin; Zheng, Hongxia; Chang, Ming-Wei; Ahmad, Zeeshan; Li, Jing-Song

    2016-09-01

    Hollow magnetic fibers for trigger based drug release were synthesized using one-step co-axial electrospinning (COX-ES). This was achieved by encapsulating the antifungal active 'ketoconazole' (KCZ) and iron oxide (Fe3O4) nanoparticles (NPs) in composite form within the core shell polymeric matrix material (polycaprolactone, PCL) during the COX-ES process. Dimethyl silicone oil was used as the inner core (liquid) of co-flowing solutions, which subsequently perfused out of the two-phase electrospun microstructures to form hollow fibers. Resulting drug-loaded magnetic hollow fibers were characterized using optical microscopy, scanning electron microscopy and Fourier Transform Infra-Red. The tensile strength and magnetization properties of composite fibers were also assessed. KCZ drug concentration in electrospinning solutions strongly influenced resulting fiber morphology, drug loading efficiency and release. Expedited drug release during a slow-sustained phase was demonstrated through the application of an auxiliary magnetic field. Variations in tensile strength (∼1.3-6.3MPa) were due to composite fiber components compromising polymer chain integrity. In-vitro cell studies (using human cervical carcinoma cell lines) demonstrated fiber biocompatibility. The present study demonstrates the potential application of magnetic hollow fibers for controlled treatment of fungal infections and antimicrobial indications. PMID:27295492

  9. Flow cytometry susceptibility testing for conventional antifungal drugs and Comparison with the NCCLS Broth Macrodilution Test

    Directory of Open Access Journals (Sweden)

    M.J. Najafzadeh

    2009-08-01

    Full Text Available Introduction: During the last decade, the incidence of fungal infection has been increased in many countries. Because of the advent of resistant to antifungal agents, determination of an efficient strategic plan for treatment of fungal disease is an important issue in clinical mycology. Many methods have been introduced and developed for determination of invitro susceptibility tests. During the recent years, flow cytometry has developed to solving the problem and many papers have documented the usefulness of this technique. Materials and methods: As the first step, the invitro susceptibility of standard PTCC (Persian Type of Culture Collection strain and some clinical isolates of Candida consisting of Candida albicans, C. dubliniensis, C. glabrata, C. kefyer and C. parapsilosis were evaluated by macrodilution broth method according to NCCLS (National Committee for Clinical Laboratory Standards guidelines and flow cytometry susceptibility test. Results:  The data indicated that macro dilution broth methods and flow cytometry have the same results in determination of MIC (Minimum Inhibitory Concentration for amphotericin B, clotrimazole, fluconazole, ketoconazole and miconazole in C. albicans PTCC 5027 as well as clinical Candida isolates, such as C.albicans, C.dubliniensis, C.glabrata C.kefyr, and C.parapsilosis. Discussion: Comparing the results obtained by macrodilution broth and flow cytometry methods revealed that flow cytometry was faster. It is suggested that flow cytometry susceptibility test can be used as a powerful tool for determination of MIC and administration of the best antifungal drug in treatment of patients with Candida infections.

  10. Mycotoxins and Antifungal Drug Interactions: Implications in the Treatment of Illnesses Due to Indoor Chronic Toxigenic Mold Exposures

    Directory of Open Access Journals (Sweden)

    Ebere C. Anyanwu

    2004-01-01

    Full Text Available Chronic exposure to toxigenic molds in water-damaged buildings is an indoor environmental health problem to which escalating health and property insurance costs are raising a statewide concern in recent times. This paper reviews the structural and functional properties of mycotoxins produced by toxigenic molds and their interactive health implications with antifungal drugs. Fundamental bases of pathophysiological, neurodevelopmental, and cellular mechanisms of mycotoxic effects are evaluated. It is most likely that the interactions of mycotoxins with antifungal drugs may, at least in part, contribute to the observable persistent illnesses, antifungal drug resistance, and allergic reactions in patients exposed to chronic toxigenic molds. Safe dose level of mycotoxin in humans is not clear. Hence, the safety regulations in place at the moment remain inconclusive, precautionary, and arbitrary. Since some of the antifungal drugs are derived from molds, and since they have structural and functional groups similar to those of mycotoxins, the knowledge of their interactions are important in enhancing preventive measures.

  11. Lemon grass (Cymbopogon citratus essential oil as a potent anti-inflammatory and antifungal drugs

    Directory of Open Access Journals (Sweden)

    Mohamed Nadjib Boukhatem

    2014-09-01

    Full Text Available Background: Volatile oils obtained from lemon grass [Cymbopogon citratus (DC. Stapf, Poaceae family] are used in traditional medicine as remedies for the treatment of various diseases. Aims: In the present study, lemon grass essential oil (LGEO was evaluated for its in vivo topical and oral anti-inflammatory effects, and for its in vitro antifungal activity using both liquid and vapor phases. Methods: The chemical profile of LGEO as determined by gas chromatography–mass spectrometry analysis revealed two major components: geranial (42.2%, and neral (31.5%. The antifungal activity of LGEO was evaluated against several pathogenic yeasts and filamentous fungi using disc diffusion and vapor diffusion methods. Results: LGEO exhibited promising antifungal effect against Candida albicans, C. tropicalis, and Aspergillus niger, with different inhibition zone diameters (IZDs (35–90 mm. IZD increased with increasing oil volume. Significantly, higher anti-Candida activity was observed in the vapor phase. For the evaluation of the anti-inflammatory effect, LGEO (10 mg/kg, administered orally significantly reduced carrageenan-induced paw edema with a similar effect to that observed for oral diclofenac (50 mg/kg, which was used as the positive control. Oral administration of LGEO showed dose-dependent anti-inflammatory activity. In addition, topical application of LGEO in vivo resulted in a potent anti-inflammatory effect, as demonstrated by using the mouse model of croton oil-induced ear edema. To our knowledge, this is the first such report to be published. The topical application of LGEO at doses of 5 and 10 µL/ear significantly reduced acute ear edema induced by croton oil in 62.5 and 75% of the mice, respectively. In addition, histological analysis clearly confirmed that LGEO inhibits the skin inflammatory response in animal models. Conclusion: Results of the present study indicate that LGEO has a noteworthy potential for the development of drugs for

  12. Triazole derivatives with improved in vitro antifungal activity over azole drugs

    Directory of Open Access Journals (Sweden)

    Yu S

    2014-04-01

    Full Text Available Shichong Yu,1,* Xiaoyun Chai,1,* Yanwei Wang,1 Yongbing Cao,2 Jun Zhang,3 Qiuye Wu,1 Dazhi Zhang,1 Yuanying Jiang,2 Tianhua Yan,4 Qingyan Sun11Department of Organic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China; 2Drug Research Center, School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China; 3Overseas Education Faculty of the Second Military Medical University, Shanghai, People's Republic of China; 4Department of Pharmacology, School of Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China*These authors contributed equally to this workAbstract: A series of triazole antifungal agents with piperidine side chains was designed and synthesized. The results of antifungal tests against eight human pathogenic fungi in vitro showed that all the compounds exhibited moderate-to-excellent activities. Molecular docking between 8d and the active site of Candida albicans CYP51 was provided based on the computational docking results. The triazole interacts with the iron of the heme group. The difluorophenyl group is located in the S3 subsite and its fluorine atom (2-F can form H-bonds with Gly307. The side chain is oriented into the S4 subsite and formed hydrophobic and van der Waals interactions with the amino residues. Moreover, the phenyl group in the side chain interacts with the phenol group of Phe380 through the formation of π–π face-to-edge interactions.Keywords: synthesis, CYP51, molecular docking, azole agents

  13. Cryptococcus neoformans isolates from Yaoundé human immunodeficiency virus-infected patients exhibited intra-individual genetic diversity and variation in antifungal susceptibility profiles between isolates from the same patient.

    Science.gov (United States)

    Kammalac Ngouana, Thierry; Drakulovski, Pascal; Krasteva, Donika; Kouanfack, Charles; Reynes, Jacques; Delaporte, Eric; Boyom, Fabrice Fekam; Mallié, Michèle; Bertout, Sebastien

    2016-07-01

    Cryptococcal meningitis is a dreadful opportunistic fungal infection amongst human immunodeficiency virus (HIV)-infected patients. One complication in the management of the disease is the possible infection of a patient by two or more different strains of Cryptococcus neoformans. This study investigated the intra-individual genetic diversity and antifungal susceptibility of C. neoformans isolates from Yaoundé (Cameroon) HIV-infected patients with cryptococcal meningitis. Twenty-five clinical isolates were obtained during a prospective study. Five colonies were randomly collected from each initial sample. The 150 isolates obtained (125 colonies and 25 initial samples) were submitted to serotyping by multiplex PCR. Genotyping analyses were achieved using RFLP, and minisatellite- and microsatellite-length polymorphism. The antifungal susceptibility testing was carried out using a Sensititre YeastOne kit. Seven antifungals were tested: itraconazole, fluconazole, amphotericin B, ketoconazole, 5-fluorocytosine, posaconazole and voriconazole. The 150 isolates were identified as C. neoformans serotype A and genotype VNI. The microsatellite and minisatellite sequence analyses generated 15 genotypes. Six out of 25 (24 %) patients were found to be infected by two different genotypes. Antifungal susceptibility showed several profiles: posaconazole (0.015-0.25 µg ml-1), amphotericin B (0.06-1 µg ml-1), fluconazole (0.5-16 µg ml-1), itraconazole (0.008-0.12 µg ml-1), ketoconazole (0.008-0.12 µg ml-1), 5-fluorocytosine (0.25-16 µg ml-1) and voriconazole (0.008-0.12 µg ml-1). It was noted that isolates from the same patient might present different susceptibility profiles to an antifungal drug with differences of more than four dilutions. The results achieved highlighted the possible presence of isolates with different genotypes in a patient with dissimilar antifungal susceptibility profiles during a single episode of cryptococcal meningitis. PMID:27100672

  14. Antifungal drug susceptibility and phylogenetic diversity among Cryptococcus isolates from dogs and cats in North America.

    Science.gov (United States)

    Singer, Lisa M; Meyer, Wieland; Firacative, Carolina; Thompson, George R; Samitz, Eileen; Sykes, Jane E

    2014-06-01

    Molecular types of the Cryptococcus neoformans/Cryptococcus gattii species complex that infect dogs and cats differ regionally and with host species. Antifungal drug susceptibility can vary with molecular type, but the susceptibility of Cryptococcus isolates from dogs and cats is largely unknown. Cryptococcus isolates from 15 dogs and 27 cats were typed using URA5 restriction fragment length polymorphism analysis (RFLP), PCR fingerprinting, and multilocus sequence typing (MLST). Susceptibility was determined using a microdilution assay (Sensititre YeastOne; Trek Diagnostic Systems). MICs were compared among groups. The 42 isolates studied comprised molecular types VGI (7%), VGIIa (7%), VGIIb (5%), VGIIc (5%), VGIII (38%), VGIV (2%), VNI (33%), and VNII (2%), as determined by URA5 RFLP. The VGIV isolate was more closely related to VGIII according to MLST. All VGIII isolates were from cats. All sequence types identified from veterinary isolates clustered with isolates from humans. VGIII isolates showed considerable genetic diversity compared with other Cryptococcus molecular types and could be divided into two major subgroups. Compared with C. neoformans MICs, C. gattii MICs were lower for flucytosine, and VGIII MICs were lower for flucytosine and itraconazole. For all drugs except itraconazole, C. gattii isolates exhibited a wider range of MICs than C. neoformans. MICs varied with Cryptococcus species and molecular type in dogs and cats, and MICs of VGIII isolates were most variable and may reflect phylogenetic diversity in this group. Because sequence types of dogs and cats reflect those infecting humans, these observations may also have implications for treatment of human cryptococcosis.

  15. Antifungal drugs as corrosion inhibitors for aluminium in 0.1 M HCl

    Energy Technology Data Exchange (ETDEWEB)

    Obot, I.B. [Department of Chemistry, Faculty of Science, University of Uyo, Uyo (Nigeria)], E-mail: proffoime@yahoo.com; Obi-Egbedi, N.O. [Department of Chemistry, University of Ibadan, Ibadan (Nigeria); Umoren, S.A. [Department of Chemistry, Faculty of Science, University of Uyo, Uyo (Nigeria)

    2009-08-15

    The inhibitive capabilities of Clotrimazole (CTM) and Fluconazole (FLC), two antifungal drugs, on the electrochemical corrosion of aluminium in 0.1 M HCl solution has been studied using weight loss measurements at 30 and 50 deg. C. The results indicate that both compound act as inhibitors in the acidic corrodent. At constant acid concentration, the inhibition efficiency (%I) increased with increase in the concentration of the inhibitors. Increase in temperature increased the corrosion rate in the absence and presence of the inhibitors but decreased the inhibition efficiency. CTM and FLC adsorbed on the surface of aluminium according to the Langmuir adsorption isotherm model at all the concentrations and temperatures studied. Phenomenon of physical adsorption is proposed from the activation parameter obtained. Thermodynamic parameters reveal that the adsorption process is spontaneous. The reactivity of these compounds was analyzed through theoretical calculations based on AM1 semi-empirical method to explain the different efficiencies of these compounds as corrosion inhibitors. CTM was found to be a better inhibitor than FLC.

  16. Antifungal drugs as corrosion inhibitors for aluminium in 0.1 M HCl

    International Nuclear Information System (INIS)

    The inhibitive capabilities of Clotrimazole (CTM) and Fluconazole (FLC), two antifungal drugs, on the electrochemical corrosion of aluminium in 0.1 M HCl solution has been studied using weight loss measurements at 30 and 50 deg. C. The results indicate that both compound act as inhibitors in the acidic corrodent. At constant acid concentration, the inhibition efficiency (%I) increased with increase in the concentration of the inhibitors. Increase in temperature increased the corrosion rate in the absence and presence of the inhibitors but decreased the inhibition efficiency. CTM and FLC adsorbed on the surface of aluminium according to the Langmuir adsorption isotherm model at all the concentrations and temperatures studied. Phenomenon of physical adsorption is proposed from the activation parameter obtained. Thermodynamic parameters reveal that the adsorption process is spontaneous. The reactivity of these compounds was analyzed through theoretical calculations based on AM1 semi-empirical method to explain the different efficiencies of these compounds as corrosion inhibitors. CTM was found to be a better inhibitor than FLC.

  17. In vitro antifungal susceptibility and molecular identity of 99 clinical isolates of the opportunistic fungal genus Curvularia.

    Science.gov (United States)

    da Cunha, Keith C; Sutton, Deanna A; Fothergill, Annette W; Gené, Josepa; Cano, Josep; Madrid, Hugo; Hoog, Sybren de; Crous, Pedro W; Guarro, Josep

    2013-06-01

    The in vitro antifungal susceptibility of a set of 99 clinical isolates of Curvularia was tested against 9 drugs using a reference microdilution method. The isolates had been identified previously to species level by comparing their ITS rDNA and glyceraldehyde-3-phosphate dehydrogenase gene sequences with those of reference strains. We were able to reliably identify 73.2% of the isolates, the most frequent species being Curvularia aeria, Curvularia geniculata/Curvularia senegalensis, Curvularia lunata, Curvularia inaequalis, Curvularia verruculosa, and Curvularia borreriae. Most of these isolates had been recovered from nasal sinus, which is generally considered one of the most frequent sites of infection by these fungi. In addition, at least 3 phylogenetic species that have not yet been formally described were detected. The most active drugs were the echinocandins, amphotericin B, and posaconazole, whereas voriconazole and itraconazole showed poor activity.

  18. 武汉地区三年来抗真菌药物应用分析%Utilization Analysis of Antifungal Drugs in 3 Consecutive Years in Wuhan

    Institute of Scientific and Technical Information of China (English)

    汪震; 刘东; 杜光

    2011-01-01

    目的:了解抗真菌类药物的临床使用情况及应用趋势.方法:对长江流域药品监测网提供的武汉地区抗真菌类药物的有关数据进行汇总,分析其药品销售金额、用药频度及排序情况.结果:抗真菌类药物的销售金额逐年增长,但以进口药品注射剂的增长为主;其中氟康唑注射液的销售金额最高,而环肽类抗真菌药物的销售金额增长最快.结论:需加强国产抗真菌类药品的研发工作,以提供更有效经济的临床选择;同时,应加强抗真菌药物的利用评价工作,进一步促进药品合理使用.%Objective: To investigate the application trend of antifungal drugs in clinics. Method; The data of antifungal drugs in Wuhan provided by Hospital Purchase of Drug Information System were collected. Then the consumption sum, frequency and order of drug use were analyzed. Result; The expenditure of antifungal drugs increased year by year and the imported injections increased more quickly than the others. The expenditure of fluconazole injections was the highest among' all the antifungal drugs. The consumption sum of echinocandins increased most quickly in antifungal drugs. Conclusion: The research on the domestic antifungal drugs should be strengthened to provide more effective and economical products. And the utilization analysis of antifungal drugs should be emphasized to promote the rational use of the medicines.

  19. Stability-indicating HPLC method development and structural elucidation of novel degradation products in posaconazole injection by LC-TOF/MS, LC-MS/MS and NMR.

    Science.gov (United States)

    Yang, Yidi; Zhu, Xi; Zhang, Fei; Li, Wei; Wu, Ying; Ding, Li

    2016-06-01

    Stress testing was carried out under acidic, alkaline, oxidative, thermal and photolytic conditions to evaluate the intrinsic stability of posaconazole injection. A total of four degradation products were detected and the drug was found to be susceptible to oxidative and thermal degradations. Three unknown degradants formed under oxidative stress condition were isolated by preparative HPLC and unambiguously elucidated by LC-TOF/MS, LC-MS/MS, (1)H NMR, (13)C NMR and 2D NMR techniques. Based on the spectrometric and spectroscopic information, these novel degradation products were unequivocally assigned as the N-oxides of posaconazole. Probable mechanisms for the formation of the degradants were proposed. A new and selective HPLC method was developed and validated to separate, detect and quantify all the degradants in posaconazole injection. PMID:27023129

  20. Progress in the study of organosulfur antifungal drugs%有机硫类抗真菌药物的研究进展

    Institute of Scientific and Technical Information of China (English)

    刘栋梁; 肖涛

    2011-01-01

    抗真菌药物(antifungal drugs)是一种用于治疗真菌感染的有效药物.近年来,天然抗真菌化合物的筛选和合成抗真菌药物的结构修饰促进了有机硫类抗真菌药物迅速发展.文中对天然有机硫类抗真菌化合物的研究进展进行了综述,同时从氮唑类、硫脲类和丙烯胺类以及硫色酮类等3类化合物的结构修饰方面综述了目前合成有机硫类抗真菌药物的研究进展.%Antifungal drugs are effective in the treatment of fungal infections. In recent years, the screening of natural antifungal compounds and structural modification of synthetic antifungal agents promote the rapid development of organosulfur antifungal drugs. The progress in the study of natural organosulfur antifungal agents and the development of the synthetic organosulfur antffungal drugs on the structural modification of azoles, thioureas and allylamines, thiochromones were reviewed.

  1. Antifungal susceptibility of clinical and environmental isolates of Cryptococcus neoformans to four antifungal drugs determined by two techniques.

    Science.gov (United States)

    Moraes, E M P; Prímola, N S; Hamdan, Júnia Soares

    2003-06-01

    A total of 64 Cryptococcus neoformans strains, including clinical and environmental Brazilian isolates var. neoformans and var. gattii, were tested for susceptibility to amphotericin B, 5-flucytosine, fluconazole and itraconazole. The tests were performed according to the recommendations of National Committee of Clinical Laboratory Standards and the method of macrodilution in liquid medium of Shadomy et al. [Manual de Microbiologia Clínica, 4th ed. Buenos Aires: Editorial Medica Panamericana, 1987: 1229-38]. For most drugs there was a significant difference between the readings taken at 24 and 48 h with both methods. When the minimum inhibitory concentrations obtained by the two techniques were compared, significant differences were observed for amphotericin B and fluconazole. Overall, differences in drug susceptibility with respect to the origin of the isolates or the variety of the fungus were not observed. As an exception, the gattii variety exhibited a high resistance rate to amphotericin B when the technique of Shadomy et al. was applied, a fact possibly related to the greater difficulty for treatment of the disease caused by this fungal variety.

  2. Synergy testing of FDA-approved drugs identifies potent drug combinations against Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Joseph D Planer

    2014-07-01

    Full Text Available An estimated 8 million persons, mainly in Latin America, are infected with Trypanosoma cruzi, the etiologic agent of Chagas disease. Existing antiparasitic drugs for Chagas disease have significant toxicities and suboptimal effectiveness, hence new therapeutic strategies need to be devised to address this neglected tropical disease. Due to the high research and development costs of bringing new chemical entities to the clinic, we and others have investigated the strategy of repurposing existing drugs for Chagas disease. Screens of FDA-approved drugs (described in this paper have revealed a variety of chemical classes that have growth inhibitory activity against mammalian stage Trypanosoma cruzi parasites. Aside from azole antifungal drugs that have low or sub-nanomolar activity, most of the active compounds revealed in these screens have effective concentrations causing 50% inhibition (EC50's in the low micromolar or high nanomolar range. For example, we have identified an antihistamine (clemastine, EC50 of 0.4 µM, a selective serotonin reuptake inhibitor (fluoxetine, EC50 of 4.4 µM, and an antifolate drug (pyrimethamine, EC50 of 3.8 µM and others. When tested alone in the murine model of Trypanosoma cruzi infection, most compounds had insufficient efficacy to lower parasitemia thus we investigated using combinations of compounds for additive or synergistic activity. Twenty-four active compounds were screened in vitro in all possible combinations. Follow up isobologram studies showed at least 8 drug pairs to have synergistic activity on T. cruzi growth. The combination of the calcium channel blocker, amlodipine, plus the antifungal drug, posaconazole, was found to be more effective at lowering parasitemia in mice than either drug alone, as was the combination of clemastine and posaconazole. Using combinations of FDA-approved drugs is a promising strategy for developing new treatments for Chagas disease.

  3. Comparison of the In Vitro Activities of Newer Triazoles and Established Antifungal Agents against Trichophyton rubrum

    NARCIS (Netherlands)

    Deng, S.; Zhang, C.; Seyedmousavi, S.; Zhu, S.; Tan, X.; Wen, Y.; Huang, X.; Lei, W.; Zhou, Z.; Fang, W.; Shen, S.; Deng, D.; Pan, W.; Liao, W.

    2015-01-01

    One hundred eleven clinical Trichophyton rubrum isolates were tested against 7 antifungal agents. The geometric mean MICs of all isolates were, in increasing order: terbinafine, 0.03 mg/liter; voriconazole, 0.05 mg/liter; posaconazole, 0.11 mg/liter; isavuconazole, 0.13 mg/liter; itraconazole, 0.26

  4. Measurement and correlation of antifungal drugs solubility in pure supercritical CO{sub 2} using semiempirical models

    Energy Technology Data Exchange (ETDEWEB)

    Yamini, Yadollah, E-mail: yyamini@modares.ac.ir [Department of Chemistry, Faculty of Sciences, Tarbiat Modares University, P.O. Box 14115-175, Tehran (Iran, Islamic Republic of); Moradi, Morteza [Department of Chemistry, Faculty of Sciences, Tarbiat Modares University, P.O. Box 14115-175, Tehran (Iran, Islamic Republic of)

    2011-07-15

    Highlights: > Ketoconazole (KZ) and clotrimazole (CZ) are two antifungal drugs. > The solubilities of KZ and CZ were measured in supercritical CO{sub 2}. > The experimental results were correlated using five density based models. > The heats' of drug-CO{sub 2} solvation and drug vaporization were estimated. - Abstract: In the present study the solubilities of two antifungal drugs of ketoconazole and clotrimazole in supercritical carbon dioxide were measured using a simple static method. The experimental data were measured at (308 to 348) K, over the pressure range of (12.2 to 35.5) MPa. The mole fraction solubilities ranged from 0.2 . 10{sup -6} to 17.45 . 10{sup -5}. In this study five density based models were used to calculate the solubility of drugs in supercritical carbon dioxide. The density based models are Chrastil, modified Chrastil, Bartle, modified Bartle and Mendez-Santiago and Teja (M-T). Interaction parameters for the studied models were obtained and the percentage of average absolute relative deviation (AARD%) in each calculation was displayed. The correlation results showed good agreement with the experimental data. A comparison among the five models revealed that the Bartle and its modified models gave much better correlations of the solubility data with an average absolute relative deviation (AARD%) ranging from 4.8% to 6.2% and from 4.5% to 6.3% for ketoconazole and clotrimazole, respectively. Using the correlation results, the heat of drug-CO{sub 2} solvation and that of drug vaporization was separately approximated in the range of (-22.1 to -26.4 and 88.3 to 125.9) kJ . mol{sup -1}.

  5. The synthesis and synergistic antifungal effects of chalcones against drug resistant Candida albicans.

    Science.gov (United States)

    Wang, Yuan-Hua; Dong, Huai-Huai; Zhao, Fei; Wang, Jie; Yan, Fang; Jiang, Yuan-Ying; Jin, Yong-Sheng

    2016-07-01

    To identify effective and low toxicity synergistic antifungal compounds, 24 derivatives of chalcone were synthesized to restore the effectiveness of fluconazole against fluconazole-resistant Candida albicans. The minimal inhibitory concentration (MIC80) and the fractional inhibitory concentration index (FICI) of the antifungal synergist fluconazole were measured against fluconazole-resistant Candida albicans. This was done via methods established by the clinical and laboratory standards institute (CLSI). Of the synthesized compounds, 2'-hydroxy-4'-methoxychalcone (8) exhibited the most potent in vitro (FICI=0.007) effects. The structure activity relationship of the compounds are then discussed. PMID:27210436

  6. Antifungal Therapy in Hematopoietic Stem Cell Transplant Recipients.

    Science.gov (United States)

    Busca, Alessandro; Pagano, Livio

    2016-01-01

    Invasive fungal infections (IFI) represent a major hindrance to the success of hematopoietic stem cell transplantation (HSCT), contributing substantially to morbidity and infection-related mortality. During the most recent years several reports indicate an overall increase of IFI among hematologic patients, in particular, invasive aspergillosis, that may be explained, at least partially, by the fact that diagnoses only suspected in the past, are now more easily established due to the application of serum biomarkers and early use of CT scan. Along with new diagnostic options, comes the recent development of novel antifungal agents that expanded the spectrum of activity over traditional treatments contributing to the successful management of fungal diseases. When introduced in 1959, Amphotericin B deoxycholate (d-AmB) was a life-saving drug, and the clinical experience over 50 years has proven that this compound is effective although toxic. Given the superior safety profile, lipid formulations of AmB have now replaced d-AmB in many circumstances. Similarly, echinocandins have been investigated as initial therapy for IA in several clinical trials including HSCT recipients, although the results were moderately disappointing leading to a lower grade of recommendation in the majority of published guidelines. Azoles represent the backbone of therapy for treating immunocompromised patients with IFI, including voriconazole and the newcomer isavuconazole; in addition, large studies support the use of mold-active azoles, namely voriconazole and posaconazole, as antifungal prophylaxis in HSCT recipients. The aim of the present review is to summarize the clinical application of antifungal agents most commonly employed in the treatment of IFI. PMID:27648202

  7. The dual role of candida glabrata drug:H+ antiporter CgAqr1 (ORF CAGL0J09944g) in antifungal drug and acetic acid resistance.

    Science.gov (United States)

    Costa, Catarina; Henriques, André; Pires, Carla; Nunes, Joana; Ohno, Michiyo; Chibana, Hiroji; Sá-Correia, Isabel; Teixeira, Miguel C

    2013-01-01

    Opportunistic Candida species often have to cope with inhibitory concentrations of acetic acid, in the acidic environment of the vaginal mucosa. Given that the ability of these yeast species to tolerate stress induced by weak acids and antifungal drugs appears to be a key factor in their persistence and virulence, it is crucial to understand the underlying mechanisms. In this study, the drug:H(+) antiporter CgAqr1 (ORF CAGL0J09944g), from Candida glabrata, was identified as a determinant of resistance to acetic acid, and also to the antifungal agents flucytosine and, less significantly, clotrimazole. These antifungals were found to act synergistically with acetic acid against this pathogen. The action of CgAqr1 in this phenomenon was analyzed. Using a green fluorescent protein fusion, CgAqr1 was found to localize to the plasma membrane and to membrane vesicles when expressed in C. glabrata or, heterologously, in Saccharomyces cerevisiae. Given its ability to complement the susceptibility phenotype of its S. cerevisiae homolog, ScAqr1, CgAqr1 was proposed to play a similar role in mediating the extrusion of chemical compounds. Significantly, the expression of this gene was found to reduce the intracellular accumulation of (3)H-flucytosine and, to a moderate extent, of (3)H-clotrimazole, consistent with a direct role in antifungal drug efflux. Interestingly, no effect of CgAQR1 deletion could be found on the intracellular accumulation of (14)C-acetic acid, suggesting that its role in acetic acid resistance may be indirect, presumably through the transport of a still unidentified physiological substrate. Although neither of the tested chemicals induces changes in CgAQR1 expression, pre-exposure to flucytosine or clotrimazole was found to make C. glabrata cells more sensitive to acetic acid stress. Results from this study show that CgAqr1 is an antifungal drug resistance determinant and raise the hypothesis that it may play a role in C. glabrata persistent colonization

  8. The dual role of Candida glabrata Drug:H+ Antiporter CgAqr1 (ORF CAGL0J09944g in antifungal drug and acetic acid resistance

    Directory of Open Access Journals (Sweden)

    Catarina eCosta

    2013-06-01

    Full Text Available Opportunistic Candida species often have to cope with inhibitory concentrations of acetic acid, in the acidic environment of the vaginal mucosa. Given that the ability of these yeast species to tolerate stress induced by weak acids and antifungal drugs appears to be a key factor in their persistence and virulence, it is crucial to understand the underlying mechanisms.In this study, the Drug:H+ Antiporter CgAqr1 (ORF CAGL0J09944g, from Candida glabrata, was identified as a determinant of resistance to acetic acid, and also to the antifungal agents flucytosine and, less significantly, clotrimazole. These antifungals were found to act synergistically with acetic acid against this pathogen. The action of CgAqr1 in this phenomenon was analyzed. Using a GFP fusion, CgAqr1 was found to localize to the plasma membrane and to membrane vesicles when expressed in C. glabrata or, heterologously, in Saccharomyces cerevisiae. Given its ability to complement the susceptibility phenotype of its S. cerevisiae homolog, ScAqr1, CgAqr1 was proposed to play a similar role in mediating the extrusion of chemical compounds. Significantly, the expression of this gene was found to reduce the intracellular accumulation of 3H-flucytosine and, to a moderate extent, of 3H-clotrimazole, consistent with a direct role in antifungal drug efflux. Interestingly, no effect of CgAQR1 deletion could be found on the intracellular accumulation of 14C-acetic acid, suggesting that its role in acetic acid resistance may be indirect, presumably through the transport of a still unidentified physiological substrate. Although neither of the tested chemicals induces changes in CgAQR1 expression, pre-exposure to flucytosine or clotrimazole was found to make C. glabrata cells more sensitive to acetic acid stress. Results from this study show that CgAqr1 is an antifungal drug resistance determinant and raise the hypothesis that it may play a role in C. glabrata persistent colonization and

  9. Exploring azole antifungal drug resistance in Aspergillus fumigatus with special reference to resistance mechanisms

    NARCIS (Netherlands)

    Chowdhary, A.; Sharma, C.; Hagen, F.; Meis, J.F.G.M.

    2014-01-01

    Aspergillus fumigatus, a ubiquitously distributed opportunistic pathogen, is the global leading cause of aspergillosis. Azole antifungals play an important role in the management of aspergillosis. However, over a decade, azole resistance in A. fumigatus isolates has been increasingly reported with v

  10. Comparison of the EUCAST and CLSI Broth Microdilution Methods for Testing Isavuconazole, Posaconazole, and Amphotericin B against Molecularly Identified Mucorales Species

    Science.gov (United States)

    Singh, Pradeep Kumar; Kathuria, Shallu; Hagen, Ferry; Meis, Jacques F.

    2015-01-01

    We compared EUCAST and CLSI antifungal susceptibility testing (AFST) methods for triazoles and amphotericin B against 124 clinical Mucorales isolates. The EUCAST method yielded MIC values 1- to 3-fold dilutions higher than those of the CLSI method for amphotericin B. The essential agreements between the two methods for triazoles were high, i.e., 99.1% (voriconazole), 98.3% (isavuconazole), and 87% (posaconazole), whereas it was significantly lower for amphotericin B (66.1%). Strategies for harmonization of the two methods for Mucorales AFST are warranted. PMID:26438489

  11. Refractory invasive aspergillosis controlled with posaconazole and pulmonary surgery in a patient with chronic granulomatous disease: case report.

    Science.gov (United States)

    Kepenekli, Eda; Soysal, Ahmet; Kuzdan, Canan; Ermerak, Nezih Onur; Yüksel, Mustafa; Bakır, Mustafa

    2014-01-01

    Invasive aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Among primary immunodefiencies, chronic granulomatous disease (CGD) has the highest prevalence of invasive fungal diseases. Voriconazole is recommended for the primary treatment of invasive aspergillosis in most patients. In patients whose aspergillosis is refractory to voriconazole, therapeutic options include changing class of antifungal, for example using an amphotericin B formulation, an echinocandin, combination therapy, or further use of azoles. Posaconazole is a triazole derivative which is effective in Aspergillosis prophylaxis and treatment. Rarely, surgical therapy may be needed in some patients. Lesions those are contiguous with the great vessels or the pericardium, single cavitary lesion that cause hemoptysis, lesions invading the chest wall, aspergillosis that involves the skin and the bone are the indications for surgical therapy.Chronic granulomatous disease (CGD) is an inherited immundeficiency caused by defects in the phagocyte nicotinamide adenine dinucleotidephosphate (NADPH) oxidase complex which is mainstay of killing microorganisms. CGD is characterized by recurrent life-threatening bacterial and fungal infections and by abnormally exuberant inflammatory responses leading to granuloma formation, such as granulomatous enteritis, genitourinary obstruction, and wound dehiscence. The diagnosis is made by neutrophil function testing and the genotyping.Herein, we present a case with CGD who had invasive pulmonary aspergillosis refractory to voriconazole and liposomal amphotericine B combination therapy that was controlled with posaconazole treatment and pulmonary surgery. PMID:24401677

  12. Structural Insights into Binding of the Antifungal Drug Fluconazole to Saccharomyces cerevisiae Lanosterol 14α-Demethylase.

    Science.gov (United States)

    Sagatova, Alia A; Keniya, Mikhail V; Wilson, Rajni K; Monk, Brian C; Tyndall, Joel D A

    2015-08-01

    Infections by fungal pathogens such as Candida albicans and Aspergillus fumigatus and their resistance to triazole drugs are major concerns. Fungal lanosterol 14α-demethylase belongs to the CYP51 class in the cytochrome P450 superfamily of enzymes. This monospanning bitopic membrane protein is involved in ergosterol biosynthesis and is the primary target of azole antifungal drugs, including fluconazole. The lack of high-resolution structural information for this drug target from fungal pathogens has been a limiting factor for the design of modified triazole drugs that will overcome resistance. Here we report the X-ray structure of full-length Saccharomyces cerevisiae lanosterol 14α-demethylase in complex with fluconazole at a resolution of 2.05 Å. This structure shows the key interactions involved in fluconazole binding and provides insight into resistance mechanisms by revealing a water-mediated hydrogen bonding network between the drug and tyrosine 140, a residue frequently found mutated to histidine or phenylalanine in resistant clinical isolates. PMID:26055382

  13. A new era for chagas disease drug discovery?

    Science.gov (United States)

    Keenan, Martine; Chaplin, Jason H

    2015-01-01

    Recent clinical trials investigating treatment of chronic indeterminate Chagas disease with two re-purposed azole anti-fungal drugs, posaconazole and ravuconazole, revealed their inferiority to the current standard-of-care benznidazole and highlighted the inadequacy of the existing pre-clinical testing paradigm for this disease. A very limited number of controlled clinical trials for Chagas disease have been conducted to date. The selection of these compounds for clinical evaluation relied heavily on pre-clinical data obtained from in vitro screens and animal studies. This chapter reviews the evolution of CYP51 as a target for Trypanosoma cruzi growth inhibition and also explores the impact of clinical trial data on contemporary Chagas disease drug discovery. Advances in pre-clinical profiling assays, the current compound landscape and progress towards the identification of new drug targets to re-invigorate research are reviewed. PMID:25727705

  14. Determination of antifungal susceptibility patterns among the environmental isolates of Aspergillus fumigatus in Iran

    Science.gov (United States)

    Mohammadi, Faezeh; Dehghan, Parvin; Nekoeian, Shahram; Hashemi, Seyed Jamal

    2016-01-01

    Background: In recent years, triazole-resistant environmental isolates of Aspergillus fumigatus have emerged in Europe and Asia. Azole resistance has been reported in patients who are treated with long-term azole therapy or exposure of the fungus spores to the azole fungicides used in agriculture. To date, a wide range of mutations in A. fumigatus have been described conferring azole-resistance, which commonly involves modifications in the cyp51A gene. We investigated antifungal susceptibility pattern of environmental isolates of A. fumigatus. Materials and Methods: In this study, 170 environmental samples collected from indoors surfaces of three hospitals in Iran. It was used β-tubulin gene to confirm the all of A. fumigatus isolates, which was identified by conventional methods. Furthermore, the antifungal susceptibility of itraconazole, voriconazole, and posaconazole was investigated using broth microdilution test, according to European Committee on Antimicrobial Susceptibility testing reference method. Results: From a total of 158 environmental molds fungi obtained from the hospitals, 58 isolates were identified as A. fumigatus by amplification of expected size of β-tubulin gene (~500 bp). In this study, in vitro antifungal susceptibility testing has shown that there were not high minimum inhibitory concentration values of triazole antifungals in all of the 58 environmental isolates of A. fumigatus. Conclusion: Our findings demonstrated that there was not azole-resistant among environmental isolates of A. fumigatus. Medical triazoles compounds have structural similarity with triazole fungicide compounds in agriculture, therefore, resistance development through exposure to triazole fungicide compounds in the environment is important but it sounds there is not a serious health problem in drug resistance in environmental isolates in Iran. PMID:27656605

  15. First description of Candida nivariensis in Brazil: antifungal susceptibility profile and potential virulence attributes

    Science.gov (United States)

    Figueiredo-Carvalho, Maria Helena Galdino; Ramos, Livia de Souza; Barbedo, Leonardo Silva; Chaves, Alessandra Leal da Silva; Muramoto, Ilda Akemi; dos Santos, André Luis Souza; Almeida-Paes, Rodrigo; Zancopé-Oliveira, Rosely Maria

    2016-01-01

    This study evaluated the antifungal susceptibility profile and the production of potential virulence attributes in a clinical strain of Candida nivariensis for the first time in Brazil, as identified by sequencing the internal transcribed spacer (ITS)1-5.8S-ITS2 region and D1/D2 domains of the 28S of the rDNA. For comparative purposes, tests were also performed with reference strains. All strains presented low planktonic minimal inhibitory concentrations (PMICs) to amphotericin B (AMB), caspofungin (CAS), and voriconazole. However, our strain showed elevated planktonic MICs to posaconazole (POS) and itraconazole, in addition to fluconazole resistance. Adherence to inert surfaces was conducted onto glass and polystyrene. The biofilm formation and antifungal susceptibility on biofilm-growing cells were evaluated by crystal violet staining and a XTT reduction assay. All fungal strains were able to bind both tested surfaces and form biofilm, with a binding preference to polystyrene (p < 0.001). AMB promoted significant reductions (≈50%) in biofilm production by our C. nivariensis strain using both methodologies. This reduction was also observed for CAS and POS, but only in the XTT assay. All strains were excellent protease producers and moderate phytase producers, but lipases were not detected. This study reinforces the pathogenic potential of C. nivariensis and its possible resistance profile to the azolic drugs generally used for candidiasis management. PMID:26814644

  16. In vitro susceptibility of antifungal drugs against Sporothrix brasiliensis recovered from cats with sporotrichosis in Brazil.

    Science.gov (United States)

    Brilhante, Raimunda Sâmia Nogueira; Rodrigues, Anderson Messias; Sidrim, José Júlio Costa; Rocha, Marcos Fábio Gadelha; Pereira, Sandro Antonio; Gremião, Isabella Dib Ferreira; Schubach, Tânia Maria Pacheco; de Camargo, Zoilo Pires

    2016-03-01

    Sporotrichosis is an important subcutaneous mycosis of humans and animals. Classically, the disease is acquired upon traumatic inoculation of Sporothrix propagules from contaminated soil and plant debris. In addition, the direct horizontal transmission of Sporothrix among animals and the resulting zoonotic infection in humans highlight an alternative and efficient rout of transmission through biting and scratching. Sporothrix brasiliensis is the most virulent species of the Sporothrix schenckii complex and is responsible for the long-lasting outbreak of feline sporotrichosis in Brazil. However, antifungal susceptibility data of animal-borne isolates is scarce. Therefore, this study evaluated the in vitro activity of amphotericin B, caspofungin, itraconazole, voriconazole, fluconazole, and ketoconazole against animal-borne isolates of S. brasiliensis. The susceptibility tests were performed through broth microdilution (M38-A2). The results show the relevant activity of itraconazole, amphotericin B, and ketoconazole against S. brasiliensis, with the following MIC ranges: 0.125-2, 0.125-4 and 0.0312-2 μg/ml, respectively. Caspofungin was moderately effective, displaying higher variation in MIC values (0.25-64 μg/ml). Voriconazole (2-64 μg/ml) and fluconazole (62.5-500 μg/ml) showed low activity against S. brasiliensis strains. This study contributed to the characterization of the in vitro antifungal susceptibility of strains of S. brasiliensis recovered from cats with sporotrichosis, which have recently been considered the main source of human infections.

  17. Clotrimazole, an antifungal drug possessing diverse actions, increases the vulnerability to cadmium in lymphocytes dissociated from rat thymus

    International Nuclear Information System (INIS)

    Since clotrimazole, known as an antifungal drug, exerts diverse actions on cellular functions, it is expected that clotrimazole can be used for other purposes. This antifungal drug protects the cells overloaded with Ca2+ by A23187, a calcium ionophore. Therefore, the agent may prevent the cells from death induced by heavy metals such as CdCl2, PbCl2, or HgCl2 that are respectively proposed to increase intracellular Ca2+ concentration. To test this possibility, we have examined the effect of clotrimazole on the cells simultaneously treated with CdCl2, PbCl2, or HgCl2 using rat thymocytes and a flow cytometer with fluorescent probes. The simultaneous application of clotrimazole and CdCl2 significantly decreased cell viability, even though the concentrations of both were ineffective at affecting the viability. The significant decrease in cell viability was not due to the inhibition of Ca2+-ATPase and Ca2+-dependent K+ channels that were induced by clotrimazole. The simultaneous application increased the population of cells with phosphatidylserine exposed on membrane surface, indicating the change in asymmetrical distribution of membrane phospholipids. Furthermore, the cytotoxicity induced by the combination of clotrimazole and CdCl2 under nominally Ca2+-free condition was more profound than that under normal Ca2+ condition. Therefore, the membrane may be a target for the cytotoxic action of clotrimazole and CdCl2 that were simultaneously applied. It is also the case for PbCl2, but not the case for HgCl2. It is concluded that clotrimazole can modulate the cytotoxicity of some heavy metals

  18. Cost-effectiveness of posaconazole versus fluconazole or itraconazole in the prevention of invasive fungal infections among high-risk neutropenic patients in Spain

    Directory of Open Access Journals (Sweden)

    Grau Santiago

    2012-04-01

    Full Text Available Abstract Background We evaluated the cost-effectiveness of posaconazole compared with standard azole therapy (SAT; fluconazole or itraconazole for the prevention of invasive fungal infections (IFI and the reduction of overall mortality in high-risk neutropenic patients with acute myelogenous leukaemia (AML or myelodysplastic syndromes (MDS. The perspective was that of the Spanish National Health Service (NHS. Methods A decision-analytic model, based on a randomised phase III trial, was used to predict IFI avoided, life-years saved (LYS, total costs, and incremental cost-effectiveness ratio (ICER; incremental cost per LYS over patients' lifetime horizon. Data for the analyses included life expectancy, procedures, and costs associated with IFI and the drugs (in euros at November 2009 values which were obtained from the published literature and opinions of an expert committee. A probabilistic sensitivity analysis (PAS was performed. Results Posaconazole was associated with fewer IFI (0.05 versus 0.11, increased LYS (2.52 versus 2.43, and significantly lower costs excluding costs of the underlying condition (€6,121 versus €7,928 per patient relative to SAT. There is an 85% probability that posaconazole is a cost-saving strategy compared to SAT and a 97% probability that the ICER for posaconazole relative to SAT is below the cost per LYS threshold of €30,000 currently accepted in Spain. Conclusions Posaconazole is a cost-saving prophylactic strategy (lower costs and greater efficacy compared with fluconazole or itraconazole in high-risk neutropenic patients.

  19. 含有额外拷贝黄曲霉cyp51同源基因的烟曲霉对抗真菌药物的敏感性测定%Antifungal susceptibility of the A.fumigatus transformants containing extra copies of A.flavus cyp51 gene homologues to the common antifungal drugs

    Institute of Scientific and Technical Information of China (English)

    刘伟霞; 孙毅; 万喆; 李若瑜; 刘伟

    2011-01-01

    Objective To investigate the effect of Aspergillus flavus cyp51 genes on antifungal susceptibility by cloning and constucting the extra copies of Aspergillus flavus cyp51 genes. Methods A.flavus cyp5l gene homologues were identified by tblastn searches inA. flavus genome database. PCR fragments composed of the 5'flanking sequence (approximately 1 000 bp) ofcyp51 ,cyp51 ORF, and its 3'flanking sequence (approximately 1 000 bp), were subcloned into shuttle plasmid pRG3-AMAl-NotI to produce recombinant plasmids. These plasmids and empty plasmid pRG3-AMA1-Notl were transformed into A.fumigatus strain AF293.1 (pyrG-) respectively to produce transformants. The Clinical Laboratory Standard Institute broth microdilution method M38-A2 and E-test method were used to assay the minimal inhibitory concentrations (MICs) of itraconazole ( ITC), voriconazole ( VRC), amphotericin B (AMB), and posaconazole (POS), or minimal effect concentration (MEC) of caspofungin (CAS), against these transformants. Results A. flavus genome contains three cyp51 gene homologues, cyp51A ,cyp51B and cyp51 C, of which the ORF size are 1 400-2 000 bp. When these genes were subcloned into shuttle plasmid pRG3-AMA1-NotI, we get plasmids pRG3-AMA1-CYP51 A, pRG3-AMA1-CYP51B and pRG3-AMA1-CYP51C. These plasmids and empty plasmid were transformed into A.fumigatus strain AF293.1 (pyrG-) to produce transformants rCYP51A, rCYP51B, rCYP51C and rpRG. The antifungal susceptibility of these A.fumigatus transformants to the antifungal drugs by broth microdilution assaying and E-test method showed that, rCYP51A and rCYP51B were cross-resistant to VRC and ITC, susceptible to both AM B and CAS; rCYP51C and rpRG were intermediate to ITC and VRC, susceptible to both A MB and CAS. Conclusion In A. fumigatus , extra copies of A.flavus ' cyp51A gene or cyp51B gene have effect on antifungal susceptibility to azoles, have no effect on AMB and CAS. Extra copy ofcyp51C has no obvious effect on all the tested drugs.%目的

  20. Analysis of drug sensitivity of candida to antifungal drugs in 152 infected patients%152例临床念珠菌感染药敏分析

    Institute of Scientific and Technical Information of China (English)

    奚琳琳; 张群智; 李芳芹

    2011-01-01

    目的 了解医院念珠菌感染药敏情况,为临床合理用药提供实验依据.方法 从临床标本中分离培养念珠菌,进行鉴定和药敏试验.结果 1 538份临床标本中分离出念珠菌152株(9.88%);其中,白色念珠菌111株(73.03%),克柔氏念珠菌31例(20.39%),其他10(6.58%).白色念珠菌时常用抗真菌药物敏感性均较高(伊曲康唑除外),而克柔氏念珠菌则对常用抗真菌药物均有较高的敏感率.结论 白色念珠菌和克柔氏念珠菌对临床一线抗真菌药氟康哇存在耐药株,应重视对高危人群进行微生物学检测和药敏试验.%Aim To investigate drug sensitivity of candida to antibiotics in patients with candida infection.Methods Candida were isolated and cultured from clinical 152 and drug sensitivity of candida to antifungal was conducted and the results were analyzed.Results A total of 152 (9.88%)candida strains were isolated from 1 538 samples,including 111 (73.03%)Candida albicans and 31 (20.39%)Candida krusei.Candida albicans showed higher sensitive rates to conventional antifungal drugs except itraconazole.However,Candida krusei showed higher sensitive rates to antifungal agents.Conclusion Candida albicans and Candida krusei showed resistances to clinical first-line antffuangal drugs such as fluconazole.Thus srug sensitivity tests be carried out to guide clinical treatment of the infections

  1. Candida albicans autophagy, no longer a bystander: Its role in tolerance to ER stress-related antifungal drugs.

    Science.gov (United States)

    Yu, Qilin; Jia, Chang; Dong, Yijie; Zhang, Bing; Xiao, Chenpeng; Chen, Yulu; Wang, Yuzhou; Li, Xiaoling; Wang, Lei; Zhang, Biao; Li, Mingchun

    2015-08-01

    Autophagy is a degradation process involved in pathogenicity of many pathogenic fungi. However, its roles in Candida albicans, the leading fungal pathogen in human beings, remain to be detailed. Most recently, we found that endoplasmic reticulum (ER) stress-inducing conditions led to transcriptional up-regulation of C. albicans autophagy-related (ATG) genes, implying a possible link between autophagy and ER stress response in this pathogen. Using a series of C. albicans ATG mutants and autophagy reporting systems, we found that both treatment of ER stress-related drugs and loss of the ER calcium pump Spf1 promoted autophagic flux of Atg8 and Lap41 (a homologue of Saccharomyces cerevisiae Ape1), indicating that these conditions induce autophagy. Moreover, deletion of ATG genes in the spf1Δ/Δ mutant rendered cells hypersensitive to these drugs and caused activation of UPR, revealing a role of autophagy in alleviating ER stress. In addition, only treatment of tunicamycin and loss of Spf1 in combination increased autophagic flux of the ER component Sec63, suggesting that most of the ER stress-related conditions cause non-selective autophagy rather than selective ER phagy. This study uncovers the important role of C. albicans autophagy in ER stress response and tolerance to antifungal drugs.

  2. Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers: II. Evaluation of the imidazole antifungal drug-loaded nanoparticle dispersions and their gel formulations

    Science.gov (United States)

    Das, Surajit; Kiong Ng, Wai; Tan, Reginald B. H.

    2014-03-01

    This study focused on: (i) feasibility of the previously developed sucrose ester stabilized SLNs and NLCs to encapsulate different imidazole antifungal drugs and (ii) preparation and evaluation of topical gel formulations of those SLNs and NLCs. Three imidazole antifungal drugs; clotrimazole, ketoconazole and climbazole were selected for this study. The results suggested that size, size distribution and drug encapsulation efficiency depend on the drug molecule and type of nanoparticles (SLN/NLC). The drug release experiment always showed faster drug release from NLCs than SLNs when the same drug molecule was loaded in both nanoparticles. However, drug release rate from both SLNs and NLCs followed the order of climbazole > ketoconazole > clotrimazole. NLCs demonstrated better physicochemical stability than SLNs in the case of all drugs. The drug release rate from ketoconazole- and clotrimazole-loaded SLNs became faster after three months than a fresh formulation. There was no significant change in drug release rate from climbazole-loaded SLNs and all drug-loaded NLCs. Gel formulations of SLNs and NLCs were prepared using polycarbophil polymer. Continuous flow measurements demonstrated non-Newtonian flow with shear-thinning behavior and thixotropy. Oscillation measurements depicted viscoelasticity of the gel formulations. Similar to nanoparticle dispersion, drug release rate from SLN- and NLC-gel was in the order of climbazole > ketoconazole > clotrimazole. However, significantly slower drug release was noticed from all gel formulations than their nanoparticle counterparts. Unlike nanoparticle dispersions, no significant difference in drug release from gel formulations containing SLNs and NLCs was observed for each drug. This study concludes that gel formulation of imidazole drug-loaded SLNs and NLCs can be used for sustained/prolonged topical delivery of the drugs.

  3. Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers: II. Evaluation of the imidazole antifungal drug-loaded nanoparticle dispersions and their gel formulations

    International Nuclear Information System (INIS)

    This study focused on: (i) feasibility of the previously developed sucrose ester stabilized SLNs and NLCs to encapsulate different imidazole antifungal drugs and (ii) preparation and evaluation of topical gel formulations of those SLNs and NLCs. Three imidazole antifungal drugs; clotrimazole, ketoconazole and climbazole were selected for this study. The results suggested that size, size distribution and drug encapsulation efficiency depend on the drug molecule and type of nanoparticles (SLN/NLC). The drug release experiment always showed faster drug release from NLCs than SLNs when the same drug molecule was loaded in both nanoparticles. However, drug release rate from both SLNs and NLCs followed the order of climbazole > ketoconazole > clotrimazole. NLCs demonstrated better physicochemical stability than SLNs in the case of all drugs. The drug release rate from ketoconazole- and clotrimazole-loaded SLNs became faster after three months than a fresh formulation. There was no significant change in drug release rate from climbazole-loaded SLNs and all drug-loaded NLCs. Gel formulations of SLNs and NLCs were prepared using polycarbophil polymer. Continuous flow measurements demonstrated non-Newtonian flow with shear-thinning behavior and thixotropy. Oscillation measurements depicted viscoelasticity of the gel formulations. Similar to nanoparticle dispersion, drug release rate from SLN- and NLC-gel was in the order of climbazole > ketoconazole > clotrimazole. However, significantly slower drug release was noticed from all gel formulations than their nanoparticle counterparts. Unlike nanoparticle dispersions, no significant difference in drug release from gel formulations containing SLNs and NLCs was observed for each drug. This study concludes that gel formulation of imidazole drug-loaded SLNs and NLCs can be used for sustained/prolonged topical delivery of the drugs. (paper)

  4. Curcumin and its promise as an anticancer drug: An analysis of its anticancer and antifungal effects in cancer and associated complications from invasive fungal infections.

    Science.gov (United States)

    Chen, Jin; He, Zheng-Min; Wang, Feng-Ling; Zhang, Zheng-Sheng; Liu, Xiu-zhen; Zhai, Dan-Dan; Chen, Wei-Dong

    2016-02-01

    Invasive fungal infections (IFI) are important complications of cancer, and they have become a major cause of morbidity and mortality in cancer patients. Effective anti-infection therapy is necessary to inhibit significant deterioration from these infections. However, they are difficult to treat, and increasing antifungal drug resistance often leads to a relapse. Curcumin, a natural component that is isolated from the rhizome of Curcuma longa plants, has attracted great interest among many scientists studying solid cancers over the last half century. Interestingly, curcumin provides an ideal alternative to current therapies because of its relatively safe profile, even at high doses. To date, curcumin's potent antifungal activity against different strains of Candida, Cryptococcus, Aspergillus, Trichosporon and Paracoccidioides have been reported, indicating that curcumin anticancer drugs may also possess an antifungal role, helping cancer patients to resist IFI complications. The aim of this review is to discuss curcumin's dual pharmacological activities regarding its applications as a natural anticancer and antifungal agent. These dual pharmacological activities are expected to lead to clinical trials and to improve infection survival among cancer patients. PMID:26723514

  5. Bibliometric analysis on hepatotoxicity due to antifungal drugs%抗真菌药肝毒性的文献计量学分析

    Institute of Scientific and Technical Information of China (English)

    白艳; 李悦; 刘斌; 王昆; 梅和坤; 张颖; 王瑾; 王睿

    2014-01-01

    Objective To investigate the research progress of hepatotoxicity due to antifungal drugs, in order to provide a reference for clinical safety use of antifungal drugs. Methods "Antifungal drugs" and"hepatotoxicity" were selected as the keywords,and PubMed,Embase,Web of Science,Chinese Academic Periodical Full-text Database China HowNet Chinese Academic Journal( CNKI ) and Chinese Biomedical Literature database( CBMdisc)were searched. All literature on hepatotoxicity due to antifungal drugs were selected. A database of literature accepted for final bibliometric study was established by using Microsoft Excel. The parameters of bibliometrics such as published time( years),the top 5 countries and institutes in publishing,literature′s type,published time( years),top 5 journals in publishing number,top 10 articles in terms of cited frequency were studied. The main content and hotspot of literature were analyzed. The clinical manifestations, mechanism, incidence and prophylactico-therapeutic measures of hepatotoxicity due to antifungal drugs were summarized. Results A total of 221 articals(193 in English,28 in Chinese)were enrolled in the study,of which 116 were original articles,49 reviews and 56 case reports. The published time of first original publication of hepatotoxicity due to antifungal drugs were 1976. The journal which published largest number of articles was Mycoses. The highest citation number of individual article was 531. The main clinical manifestations were weak,right upper quadrant pain,diarrhea,jaundice,cholestasis and fever. The severe cases could cause liver failure. Laboratory examination showed elevated serum transaminases,bilirubin, and alkaline phosphatase. The incidence of liver toxicity due to azole antifungals was higher,the incidence of liver toxicity due to amphotericin B was lower. The antifungal drugs should be used with caution in patients with hypohepatia. For the patients who used antifungal drugs for long time,the liver function should

  6. 抗真菌药肝毒性的文献计量学分析%Bibliometric analysis on hepatotoxicity due to antifungal drugs

    Institute of Scientific and Technical Information of China (English)

    白艳; 李悦; 刘斌; 王昆; 梅和坤; 张颖; 王瑾; 王睿

    2014-01-01

    目的了解抗真菌药肝毒性的研究情况及其临床特征,为安全使用抗真菌药提供参考。方法以“antifungal drugs”和“hepatotoxicity”“、抗真菌药”和“肝毒性”为检索词,检索PubMed、Embase、Web of Science、中国知网中国期刊全文数据库和中国生物医学文献数据库收录的抗真菌药肝毒性文献,用Excel表对最终纳入的文献建立评价数据库,录入文献的发表年代、发文量排序前5位的国家及研究机构、文献类型、载文量前5位的期刊、被引频次前10位的文献等。分析有关文献的研究内容和热点,总结抗真菌药肝毒性的临床表现、发生机制及预防措施。结果共纳入文献221篇,其中英文文献193篇,中文文献28篇;论著116篇,综述49篇,病例报告56篇。首次发表抗真菌药肝毒性文献的时间是1976年,载文量最高的期刊是Mycoses,单篇文章的最高被引频次为531次。抗真菌药致肝损伤的临床表现为乏力、右上腹疼痛、腹泻、黄疸、胆汁淤积和发热等,严重者可致肝衰竭。实验室检查可见血清转氨酶、胆红素、碱性磷酸酶升高。唑类抗真菌药致肝损伤发生率较高,两性霉素B致肝损伤发生率较低。肝功能不全者应慎用抗真菌药。长期应用抗真菌药者应注意定期监测肝功能,出现肝损伤后立即停药并采取对症与保肝治疗,部分患者的肝功能可恢复至用药前水平。抗真菌药肝毒性的机制尚不完全清楚,可能与细胞质膜结构完整性受损或抑制细胞色素P4502D6酶代谢有关。结论国内对抗真菌药肝毒性的研究逊于国外;部分抗真菌药所致肝毒性呈可逆性。%Objective To investigate the research progress of hepatotoxicity due to antifungal drugs, in order to provide a reference for clinical safety use of antifungal drugs. Methods "Antifungal drugs" and"hepatotoxicity" were selected as the keywords

  7. Comparative study on the effects of two antifungal drugs against Candida albicans by microcalorimetry and transmission electron microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Qing-Lian [Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Zhang, Juan [Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Department of Stomatology, Hubei Provincial Maternal and Child Health Hospital, Wuhan 430070 (China); Xu, Zi-Qiang; Li, Ran [State Key Laboratory of Virology and Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072 (China); Jiang, Feng-Lei, E-mail: fljiang@whu.edu.cn [State Key Laboratory of Virology and Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072 (China); Xiao, Qi, E-mail: qi.xiao@whu.edu.cn [College of Chemistry and Life Science, Guangxi Teachers Education University, Nanning 530001 (China); Liu, Yi [State Key Laboratory of Virology and Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072 (China)

    2012-09-10

    Highlights: Black-Right-Pointing-Pointer Microcalorimetry is a fast, simple method to study the antibiotic property of drugs. Black-Right-Pointing-Pointer We noticed that the antibiotic effect of ITZ was slightly better than that of KTZ. Black-Right-Pointing-Pointer We perform the TEM to study the morphology changes of C. albicans cells. - Abstract: In this work, a multi-channel thermal activity monitor (TAM 2277) was applied to study the growth metabolism of Candida albicans (C. albicans) in vitro in the absence and presence of different concentrations of ketoconazole (KTZ) and itraconazole (ITZ). The results showed that the half inhibiting concentrations (IC{sub 50}) of C. albicans by KTZ and ITZ are 73.5 and 66.3 {mu}mol L{sup -1}, respectively. So the antibiotic effect of ITZ was slightly better than that of KTZ. The morphology of C. albicans cells both in the absence and presence of antifungal agents was examined by transmission electron microscopy (TEM). Our research also suggests that microcalorimetry is a fast, simple, non-invasive, non-destructive and more sensitive method, and can be easily performed to study the antibiotic property of different species of drugs on microorganism compared to other biological and clinical methods.

  8. Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent.

    Directory of Open Access Journals (Sweden)

    Hye Ji Cha

    Full Text Available Studies in diverse organisms have revealed a surprising depth to the evolutionary conservation of genetic modules. For example, a systematic analysis of such conserved modules has recently shown that genes in yeast that maintain cell walls have been repurposed in vertebrates to regulate vein and artery growth. We reasoned that by analyzing this particular module, we might identify small molecules targeting the yeast pathway that also act as angiogenesis inhibitors suitable for chemotherapy. This insight led to the finding that thiabendazole, an orally available antifungal drug in clinical use for 40 years, also potently inhibits angiogenesis in animal models and in human cells. Moreover, in vivo time-lapse imaging revealed that thiabendazole reversibly disassembles newly established blood vessels, marking it as vascular disrupting agent (VDA and thus as a potential complementary therapeutic for use in combination with current anti-angiogenic therapies. Importantly, we also show that thiabendazole slows tumor growth and decreases vascular density in preclinical fibrosarcoma xenografts. Thus, an exploration of the evolutionary repurposing of gene networks has led directly to the identification of a potential new therapeutic application for an inexpensive drug that is already approved for clinical use in humans.

  9. Comparative study on the effects of two antifungal drugs against Candida albicans by microcalorimetry and transmission electron microscopy

    International Nuclear Information System (INIS)

    Highlights: ► Microcalorimetry is a fast, simple method to study the antibiotic property of drugs. ► We noticed that the antibiotic effect of ITZ was slightly better than that of KTZ. ► We perform the TEM to study the morphology changes of C. albicans cells. - Abstract: In this work, a multi-channel thermal activity monitor (TAM 2277) was applied to study the growth metabolism of Candida albicans (C. albicans) in vitro in the absence and presence of different concentrations of ketoconazole (KTZ) and itraconazole (ITZ). The results showed that the half inhibiting concentrations (IC50) of C. albicans by KTZ and ITZ are 73.5 and 66.3 μmol L−1, respectively. So the antibiotic effect of ITZ was slightly better than that of KTZ. The morphology of C. albicans cells both in the absence and presence of antifungal agents was examined by transmission electron microscopy (TEM). Our research also suggests that microcalorimetry is a fast, simple, non-invasive, non-destructive and more sensitive method, and can be easily performed to study the antibiotic property of different species of drugs on microorganism compared to other biological and clinical methods.

  10. Antibody Peptide Based Antifungal Immunotherapy

    OpenAIRE

    Magliani, Walter; Conti, Stefania; Giovati, Laura; Zanello, Pier Paolo; Sperindè, Martina; Ciociola, Tecla; Polonelli, Luciano

    2012-01-01

    Fungal infections still represent relevant human illnesses worldwide and some are accompanied by unacceptably high mortality rates. The limited current availability of effective and safe antifungal agents makes the development of new drugs and approaches of antifungal vaccination/immunotherapy every day more needed. Among them, small antibody(Ab)-derived peptides are arousing great expectations as new potential antifungal agents. In this topic, the search path from the study of the yeast kill...

  11. Yeasts acquire resistance secondary to antifungal drug treatment by adaptive mutagenesis.

    Directory of Open Access Journals (Sweden)

    David Quinto-Alemany

    Full Text Available Acquisition of resistance secondary to treatment both by microorganisms and by tumor cells is a major public health concern. Several species of bacteria acquire resistance to various antibiotics through stress-induced responses that have an adaptive mutagenesis effect. So far, adaptive mutagenesis in yeast has only been described when the stress is nutrient deprivation. Here, we hypothesized that adaptive mutagenesis in yeast (Saccharomyces cerevisiae and Candida albicans as model organisms would also take place in response to antifungal agents (5-fluorocytosine or flucytosine, 5-FC, and caspofungin, CSP, giving rise to resistance secondary to treatment with these agents. We have developed a clinically relevant model where both yeasts acquire resistance when exposed to these agents. Stressful lifestyle associated mutation (SLAM experiments show that the adaptive mutation frequencies are 20 (S. cerevisiae -5-FC, 600 (C. albicans -5-FC or 1000 (S. cerevisiae--CSP fold higher than the spontaneous mutation frequency, the experimental data for C. albicans -5-FC being in agreement with the clinical data of acquisition of resistance secondary to treatment. The spectrum of mutations in the S. cerevisiae -5-FC model differs between spontaneous and acquired, indicating that the molecular mechanisms that generate them are different. Remarkably, in the acquired mutations, an ectopic intrachromosomal recombination with an 87% homologous gene takes place with a high frequency. In conclusion, we present here a clinically relevant adaptive mutation model that fulfils the conditions reported previously.

  12. Thermo-acoustical analysis of sodium dodecyl sulfate: Fluconazole (antifungal drug) based micellar system in hydro-ethanol solutions for potential drug topical application

    International Nuclear Information System (INIS)

    Highlights: • The mixed micellar system was analyzed for sodium dodecyl sulfate and fluconazole. • Early micellization was found with CMC shift towards lower surfactant concentration. • Negative ΔGmo values suggested that the micelle formation is spontaneous and feasible. • Thermo-acoustical parameters revealed the existence of intermolecular interactions within the molecules. - Abstract: Micellar systems hold excellent drug delivery applications due to their capability to solubilize a large number of hydrophobic and hydrophilic molecules. In this present work, the mixed micelle formation between the anionic surfactant sodium dodecyl sulfate (SDS) and the ‘Azole’ derivative antifungal drug fluconazole (FLZ) have been studied at four temperatures in different hydro-ethanolic solutions. The critical micelle concentration (CMC) was determined by specific conductance techniques and the experimental data was used to calculate several useful thermodynamic parameters, like standard free energy, enthalpy and entropy of micelle formation. Early micellization was found with critical micelle concentration shifting towards lower concentration (CMC) than the standard concentration of SDS in water at 25 °C suggesting that drug and the solvent system facilitates the micellization process. In addition, the transport properties were examined by employing controlled approaches likely, apparent molar volume (ϕv), apparent molar adiabatic compression (ϕk), and isentropic compression (κs) of SDS in presence of FLZ. These parameters revealed the existence of intermolecular interactions within the molecules. Therefore, this study would cast light on utilizing surfactant immobilized FLZ system for better topical biological action

  13. 21 CFR 333.210 - Antifungal active ingredients.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Antifungal active ingredients. 333.210 Section 333.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Antifungal Drug Products § 333.210 Antifungal active ingredients. The active ingredient of the...

  14. Antibacterial and antifungal activity of Terminalia arjuna Wight & Arn. bark against multi-drug resistant clinical isolates

    Institute of Scientific and Technical Information of China (English)

    Sukalyani Debnath; Diganta Dey; Sudipta Hazra; Subhalakshmi Ghosh; Ratnamala Ray; Banasri Hazra

    2013-01-01

    Objective: To evaluate antimicrobial activity of Terminalia arjuna (T. arjuna) bark against clinical strains of multi-drug resistant bacteria, and Candida spp. isolated from patients, as well as the corresponding reference strains.Methods:were evaluated by agar-well diffusion method, followed by determination of minimum inhibitory concentration (MIC) by broth micro-dilution method. The clinical isolates were studied for antibacterial susceptibility by Kirby and Bauer disk diffusion technique. The antimicrobial activity of water, methanol and chloroform extracts of T. arjuna bark Results: The water and methanolic extracts of T. arjuna bark produced significant zones of inhibition against twenty-two tested bacteria including eight uropathogens. MIC values against the bacteria were found in the range of 0.16 to 2.56 mg/mL. The chloroform extract did not exhibit antibacterial activity. The polar extracts of T. arjuna also demonstrated strong antifungal effect against eight species of Candida, with MIC between 0.16 and 0.64 mg/mL. The antimicrobial efficacy of the polar extracts was found to be commensurate with high polyphenol content in contrast to the non-polar (chloroform fraction). Conclusions: This study has revealed the therapeutic prospect of T. arjuna bark for the treatment of microbial diseases. The polar fraction of the bark could be used for development of novel antimicrobial agents, particularly against urinary tract infections, and candidiasis/candidaemia.

  15. In vitro interactions of antifungal agents and tacrolimus against Aspergillus biofilms.

    Science.gov (United States)

    Gao, Lujuan; Sun, Yi

    2015-11-01

    Aspergillus biofilms were prepared from Aspergillus fumigatus, Aspergillus flavus, and Aspergillus terreus via a 96-well plate-based method, and the combined antifungal activity of tacrolimus with azoles or amphotericin B against Aspergillus biofilms was investigated via a broth microdilution checkerboard technique system. Our results suggest that combinations of tacrolimus with voriconazole or amphotericin B have synergistic inhibitory activity against Aspergillus biofilms. However, combinations of tacrolimus with itraconazole or posaconazole exhibit no synergistic or antagonistic effects.

  16. Role of Multidrug Resistance Protein 3 in Antifungal-Induced Cholestasis.

    Science.gov (United States)

    Mahdi, Zainab M; Synal-Hermanns, Uta; Yoker, Aylin; Locher, Kaspar P; Stieger, Bruno

    2016-07-01

    Drug-induced liver injury is an important clinical entity resulting in a considerable number of hospitalizations. While drug-induced cholestasis due to the inhibition of the bile salt export pump (BSEP) is well investigated, only limited information on the interaction of drugs with multidrug resistance protein 3 (MDR3) exists and its role in the pathogenesis of drug-induced cholestasis is poorly understood. Therefore, we aimed to study the interaction of drugs with MDR3 and the effect of drugs on canalicular lipid secretion in a newly established polarized cell line system that serves as a model of canalicular lipid secretion. LLC-PK1 cells were stably transfected with human Na(+)-taurocholate cotransporting polypeptide, BSEP, MDR3, and ABCG5/G8 and grown in the Transwell system. Apical phospholipid secretion and taurocholate transport were assayed to investigate the effect of selected drugs on MDR3-mediated phospholipid secretion as well as inhibition of BSEP. The established cell line displayed vectorial bile salt transport and specific phosphatidylcholine secretion into the apical compartment. The antifungal azoles, posaconazole, itraconazole, and ketoconazole, significantly inhibited MDR3-mediated phosphatidylcholine secretion. In contrast, amoxicillin clavulanate and troglitazone did not interfere with MDR3 activity. Drugs interfering with MDR3 activity did not display a parallel inhibition of BSEP. Our in vitro model for MDR3-mediated phospholipid secretion facilitates parallel screening for MDR3 and BSEP inhibitors. Our data demonstrate that the cholestatic potential of certain drugs may be aggravated by simultaneous inhibition of BSEP and MDR3. PMID:27112167

  17. Antifungal therapy with an emphasis on biofilms

    OpenAIRE

    Pierce, Christopher G.; Srinivasan, Anand; Uppuluri, Priya; Anand K. Ramasubramanian; López-Ribot, José Luis

    2013-01-01

    Fungal infections are on the rise as advances in modern medicine prolong the lives of severely ill patients. Fungi are eukaryotic organisms and there are a limited number of targets for antifungal drug development; as a result the antifungal arsenal is exceedingly limited. Azoles, polyenes and echinocandins, constitute the mainstay of antifungal therapy for patients with life-threatening mycoses. One of the main factors complicating antifungal therapy is the formation of fungal biofilms, micr...

  18. Study the interactions between human serum albumin and two antifungal drugs: fluconazole and its analogue DTP.

    Science.gov (United States)

    Zhang, Shao-Lin; Yao, Huankai; Wang, Chenyin; Tam, Kin Y

    2014-11-01

    Binding affinities of fluconazole and its analogue 2-(2,4-dichlorophenyl)-1,3-di(1H-1,2,4-triazol-yl)-2-propanol (DTP) to human serum albumin (HSA) were investigated under approximately human physiological conditions. The obtained result indicated that HSA could generate fluorescent quenching by fluconazole and DTP because of the formation of non-fluorescent ground-state complexes. Binding parameters calculated from the Stern-Volmer and the Scatchard equations showed that fluconazole and DTP bind to HSA with binding affinities of the order 10(4)L/mol. The thermodynamic parameters revealed that the binding was characterized by negative enthalpy and positive entropy changes, suggesting that the binding reaction was exothermic. Hydrogen bonds and hydrophobic interaction were found to be the predominant intermolecular forces stabilizing the drug-protein. The effect of metal ions on the binding constants of fluconazole-HSA complex suggested that the presence of Mg(2+) and Zn(2+) ions could decrease the free drug level and extend the half-life in the systematic circulation. Docking experiments revealed that fluconazole and DTP binds in HSA mainly by hydrophobic interaction with the possibility of hydrogen bonds formation between the drugs and the residues Arg 222, Lys 199 and Lys 195 in HSA.

  19. Evaluation of the Effects of Photodynamic Therapy Alone and Combined with Standard Antifungal Therapy on Planktonic Cells and Biofilms of Fusarium spp. and Exophiala spp.

    Science.gov (United States)

    Gao, Lujuan; Jiang, Shaojie; Sun, Yi; Deng, Meiqi; Wu, Qingzhi; Li, Ming; Zeng, Tongxiang

    2016-01-01

    Infections of Fusarium spp. and Exophiala spp. are often chronic, recalcitrant, resulting in significant morbidity, causing discomfort, disfigurement, social isolation. Systemic disseminations happen in compromised patients, which are often refractory to available antifungal therapies and thereby lead to death. The antimicrobial photodynamic therapy (aPDT) has been demonstrated to effectively inactivate multiple pathogenic fungi and is considered as a promising alternative treatment for mycoses. In the present study, we applied methylene blue (8, 16, and 32 μg/ml) as a photosensitizing agent and light emitting diode (635 ± 10 nm, 12 and 24 J/cm2), and evaluated the effects of photodynamic inactivation on five strains of Fusarium spp. and five strains of Exophiala spp., as well as photodynamic effects on in vitro susceptibility to itraconazole, voriconazole, posaconazole and amphotericin B, both planktonic and biofilm forms. Photodynamic therapy was efficient in reducing the growth of all strains tested, exhibiting colony forming unit-reductions of up to 6.4 log10 and 5.6 log10 against planktonic cultures and biofilms, respectively. However, biofilms were less sensitive since the irradiation time was twice longer than that of planktonic cultures. Notably, the photodynamic effects against Fusarium strains with high minimal inhibitory concentration (MIC) values of ≥16, 4-8, 4-8, and 2-4 μg/ml for itraconazole, voriconazole, posaconazole and amphotericin B, respectively, were comparable or even superior to Exophiala spp., despite Exophiala spp. showed relatively better antifungal susceptibility profile. MIC ranges against planktonic cells of both species were up to 64 times lower after aPDT treatment. Biofilms of both species showed high sessile MIC50 (SMIC50) and SMIC80 of ≥16 μg/ml for all azoles tested and variable susceptibilities to amphotericin B, with SMIC ranging between 1 and 16 μg/ml. Biofilms subjected to aPDT exhibited a distinct reduction in SMIC

  20. Epidemiological changes with potential implication for antifungal prescription recommendations for fungaemia

    DEFF Research Database (Denmark)

    Arendrup, M C; Dzajic, E; Jensen, R H;

    2013-01-01

    .7%, itraconazole 69.6%, posaconazole 64.2% and voriconazole 85.0%. Acquired echinocandin resistance was molecularly confirmed in three isolates. The use of systemic antifungals doubled over the last decade (2002-2011) (from 717 000 to 1 450 000 defined daily doses/year) of which the vast majority (96.9%) were...... azoles. The incidence of fungaemia continues to increase in Denmark and is associated with a decreasing proportion being susceptible to fluconazole. Changes in demography, higher incidence in the elderly and higher antifungal consumption can at least in part explain the changes. © 2013 The Authors...

  1. In Vitro and In Vivo Efficacy of Amphotericin B Combined with Posaconazole against Experimental Disseminated Sporotrichosis

    Science.gov (United States)

    Mario, Débora Nunes; Guarro, Josep; Santurio, Janio Morais; Alves, Sydney Hartz

    2015-01-01

    We evaluated the combination of posaconazole with amphotericin B in vitro and in a murine model of systemic infections caused by Sporothrix brasiliensis and Sporothrix schenckii sensu stricto. In vitro data demonstrated a synergistic effect, and although posaconazole alone was effective against sporotrichosis, efficacy in terms of survival and burden reduction was increased with the combination. This combination might be an option against disseminated sporotrichosis, especially when itraconazole or amphotericin B at optimal doses are contraindicated. PMID:26014930

  2. Secondary metabolite profiles and antifungal drug susceptibility of Aspergillus fumigatus and closely related species, Aspergillus lentulus, Aspergillus udagawae, and Aspergillus viridinutans.

    Science.gov (United States)

    Tamiya, Hiroyuki; Ochiai, Eri; Kikuchi, Kazuyo; Yahiro, Maki; Toyotome, Takahito; Watanabe, Akira; Yaguchi, Takashi; Kamei, Katsuhiko

    2015-05-01

    The incidence of Aspergillus infection has been increasing in the past few years. Also, new Aspergillus fumigatus-related species, namely Aspergillus lentulus, Aspergillus udagawae, and Aspergillus viridinutans, were shown to infect humans. These fungi exhibit marked morphological similarities to A. fumigatus, albeit with different clinical courses and antifungal drug susceptibilities. The present study used liquid chromatography/time-of-flight mass spectrometry to identify the secondary metabolites secreted as virulence factors by these Aspergillus species and compared their antifungal susceptibility. The metabolite profiles varied widely among A. fumigatus, A. lentulus, A. udagawae, and A. viridinutans, producing 27, 13, 8, and 11 substances, respectively. Among the mycotoxins, fumifungin, fumiquinazoline A/B and D, fumitremorgin B, gliotoxin, sphingofungins, pseurotins, and verruculogen were only found in A. fumigatus, whereas auranthine was only found in A. lentulus. The amount of gliotoxin, one of the most abundant mycotoxins in A. fumigatus, was negligible in these related species. In addition, they had decreased susceptibility to antifungal agents such as itraconazole and voriconazole, even though metabolites that were shared in the isolates showing higher minimum inhibitory concentrations than epidemiological cutoff values were not detected. These strikingly different secondary metabolite profiles may lead to the development of more discriminative identification protocols for such closely related Aspergillus species as well as improved treatment outcomes.

  3. Monitoring of antifungal drugs in biological samples using ultrasonic-assisted supramolecular dispersive liquid-liquid microextraction based on solidification of a floating organic droplet.

    Science.gov (United States)

    Ezoddin, Maryam; Abdi, Khosrou

    2016-08-01

    A new method for the simultaneous determination of the three antifungal drugs using ultrasonic-assisted supramolecular dispersive liquid-liquid microextraction based on solidification of a floating organic droplet (UASMDLLME-SFO) was proposed. The supramolecular solvents produced from reversed micelles of 1-dodecanol (extraction solvent) in tetrahydrofuran (THF) were injected into the aqueous sample solution. Reverse micelle coacervates were produced in situ through self-assembly processes. The antifungal drugs were extracted from the aqueous sample into a supramolecular solvent. Sonication accelerated the mass transfer of the target analytes into the supramolecular solvent phase and enhanced the dispersion process. Some parameters affecting the extraction efficiency such as type and volume of the extraction solvent, pH, volume of the disperser solvent and ultrasound extraction time were investigated. Under optimum conditions, the limits of detections for ketoconazole, clotrimazole and miconazole ranged from 0.08 to 1.3μgL(-1) and the relative standard deviations (RSDs, n=5)<6% were obtained. The method was successfully applied for preconcentration of the three drugs in biological and water samples. PMID:27262083

  4. Economic Evaluation of Posaconazole Versus Standard Azole Therapy as Prophylaxis against Invasive Fungal Infections in Patients with Prolonged Neutropenia in Canada

    Directory of Open Access Journals (Sweden)

    Amir A Tahami Monfared

    2012-01-01

    Full Text Available INTRODUCTION: Posaconazole prophylaxis in high-risk neutropenic patients prevents invasive fungal infection (IFI. An economic model was used to assess the cost effectiveness of posaconazole from a Canadian health care system perspective.

  5. Topical antifungals for seborrhoeic dermatitis

    OpenAIRE

    Okokon, Enembe O; Verbeek, Jos H.; Ruotsalainen, Jani H; Ojo, Olumuyiwa A; Bakhoya, Victor Nyange

    2015-01-01

    Background Seborrhoeic dermatitis is a chronic inflammatory skin condition that is distributed worldwide. It commonly affects the scalp, face and flexures of the body. Treatment options include antifungal drugs, steroids, calcineurin inhibitors, keratolytic agents and phototherapy. Objectives To assess the effects of antifungal agents for seborrhoeic dermatitis of the face and scalp in adolescents and adults. A secondary objective is to assess whether the same interventions are effective in t...

  6. Design or screening of drugs for the treatment of Chagas disease: what shows the most promise?

    Science.gov (United States)

    Lepesheva, Galina I.

    2013-01-01

    Introduction Endemic in Latin America, Chagas disease is now becoming a serious global health problem, and yet has no financial viability for the pharmaceutical industry and remains incurable. In 2012, two antimycotic drugs inhibitors of fungal sterol 14α-demethylase (CYP51) – posaconazole and ravuconazole – entered clinical trials. Availability of the X-ray structure of the orthologous enzyme from the causative agent of the disease, protozoan parasite Trypanosoma cruzi, determined in complexes with posaconazole as well as with several experimental protozoa-specific CYP51 inhibitors opens an excellent opportunity to improve the situation. Areas covered This article summarizes the information available in PubMed and Google on the outcomes of treatment of the chronic Chagas disease. It also outlines the major features of the T. cruzi CYP51 structure and the possible structure-based strategies for rational design of novel T. cruzi specific drugs. Expert opinion There is no doubt that screenings for alternative drug-like molecules as well as mining the T. cruzi genome for novel drug targets are of great value and might eventually lead to groundbreaking discoveries. However, all newly identified molecules must proceed through the long, expensive and low-yielding drug optimization process, and all novel potential drug targets must be validated in terms of their essentiality and druggability. CYP51 is already a well-validated and highly successful target for clinical and agricultural antifungals. With minimal investments into the final stages of their development/trials, T. cruzi-specific CYP51 inhibitors can provide an immediate treatment for Chagas disease, either on their own or in combination with the currently available drugs. PMID:24079515

  7. Comparative Evaluation of FUNGITEST and Broth Microdilution Methods for Antifungal Drug Susceptibility Testing of Candida Species and Cryptococcus neoformans

    OpenAIRE

    Davey, Kate G.; Holmes, Ann D.; Elizabeth M. Johnson; Szekely, Adrien; Warnock, David W.

    1998-01-01

    The FUNGITEST method (Sanofi Diagnostics Pasteur, Paris, France) is a microplate-based procedure for the breakpoint testing of six antifungal agents (amphotericin B, flucytosine, fluconazole, itraconazole, ketoconazole, and miconazole). We compared the FUNGITEST method with a broth microdilution test, performed according to National Committee for Clinical Laboratory Standards document M27-A guidelines, for determining the in vitro susceptibilities of 180 isolates of Candida spp. (50 C. albica...

  8. Treating chromoblastomycosis with systemic antifungals.

    Science.gov (United States)

    Bonifaz, Alexandro; Paredes-Solís, Vanessa; Saúl, Amado

    2004-02-01

    Chromoblastomycosis is a subcutaneous mycosis for which there is no treatment of choice but rather, several treatment options, with low cure rates and many relapses. The choice of treatment should consider several conditions, such as the causal agent (the most common one being Fonsecaea pedrosoi ), extension of the lesions, clinical topography and health status of the patient. Most oral and systemic antifungals have been used; the best results have been obtained with itraconazole and terbinafine at high doses, for a mean of 6 - 12 months. In extensive and refractory cases, chemotherapy with oral antifungals may be associated with thermotherapy (local heat and/or cryosurgery). Limited or early cases may be managed with surgical methods, always associated with oral antifungal agents. It is important to determine the in vitro sensitivity of the major causal agents to the various drugs, by estimating the minimum inhibitory concentration, as well as drug tolerability and drug interactions.

  9. Controlled nail delivery of a novel lipophilic antifungal agent using various modern drug carrier systems as well as in vitro and ex vivo model systems.

    Science.gov (United States)

    Naumann, Sandy; Meyer, Jean-Philippe; Kiesow, Andreas; Mrestani, Yahya; Wohlrab, Johannes; Neubert, Reinhard H H

    2014-04-28

    The penetration behavior into human nails and animal hoof membranes of a novel antifungal agent (EV-086K) for the treatment of onychomycosis was investigated in this study. The new drug provides a high lipophilicity which is adverse for penetration into nails. Therefore, four different formulations were developed, with particular focus on a colloidal carrier system (CCS) due to its penetration enhancing properties. On the one hand, ex vivo penetration experiments on human nails were performed. Afterwards the human nail plates were cut by cryomicrotome in order to quantify the drug concentration in the dorsal, intermediate and ventral nail layer using high-performance liquid chromatography (HPLC) with UV detection. On the other hand, equine and bovine hoof membranes were used to determine the in vitro penetration of the drug into the acceptor compartment of an online diffusion cell coupled with Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy. In combination, both results should exhibit a correlation between the EV-086K penetration behavior in human nail plates and animal hoof membranes. The investigations showed that the developed CCS could increase drug delivery through the human nail most compared to other formulations (nail lacquer, solution and hydrogel). Using animal hooves in the online diffusion cell, we were able to calculate pharmacokinetic data of the penetration process, especially diffusion and permeability coefficients. Finally, a qualitative correlation between the penetration results of human nails and equine hooves was established. PMID:24560884

  10. Controlled nail delivery of a novel lipophilic antifungal agent using various modern drug carrier systems as well as in vitro and ex vivo model systems.

    Science.gov (United States)

    Naumann, Sandy; Meyer, Jean-Philippe; Kiesow, Andreas; Mrestani, Yahya; Wohlrab, Johannes; Neubert, Reinhard H H

    2014-04-28

    The penetration behavior into human nails and animal hoof membranes of a novel antifungal agent (EV-086K) for the treatment of onychomycosis was investigated in this study. The new drug provides a high lipophilicity which is adverse for penetration into nails. Therefore, four different formulations were developed, with particular focus on a colloidal carrier system (CCS) due to its penetration enhancing properties. On the one hand, ex vivo penetration experiments on human nails were performed. Afterwards the human nail plates were cut by cryomicrotome in order to quantify the drug concentration in the dorsal, intermediate and ventral nail layer using high-performance liquid chromatography (HPLC) with UV detection. On the other hand, equine and bovine hoof membranes were used to determine the in vitro penetration of the drug into the acceptor compartment of an online diffusion cell coupled with Fourier transform infrared attenuated total reflectance (FTIR-ATR) spectroscopy. In combination, both results should exhibit a correlation between the EV-086K penetration behavior in human nail plates and animal hoof membranes. The investigations showed that the developed CCS could increase drug delivery through the human nail most compared to other formulations (nail lacquer, solution and hydrogel). Using animal hooves in the online diffusion cell, we were able to calculate pharmacokinetic data of the penetration process, especially diffusion and permeability coefficients. Finally, a qualitative correlation between the penetration results of human nails and equine hooves was established.

  11. Hrk1 plays both Hog1-dependent and -independent roles in controlling stress response and antifungal drug resistance in Cryptococcus neoformans.

    Directory of Open Access Journals (Sweden)

    Seo-Young Kim

    Full Text Available The HOG (High Osmolarity Glycerol response pathway plays a central role in controlling stress response, ergosterol biosynthesis, virulence factor production, and differentiation of Cryptococcus neoformans, which causes fatal fungal meningoencephalitis. Recent transcriptome analysis of the HOG pathway discovered a Hog1-regulated gene (CNAG_00130.2, encoding a putative protein kinase orthologous to Rck1/2 in Saccharomyces cerevisiae and Srk1 in Schizosaccharomyces pombe. Its function is not known in C. neoformans. The present study functionally characterized the role of Hrk1 in C. neoformans. Northern blot analysis confirmed that HRK1 expression depends on the Hog1 MAPK. Similar to the hog1Δ mutant, the hrk1Δ mutant exhibited almost complete resistance to fludioxonil, which triggers glycerol biosynthesis via the HOG pathway. Supporting this, the hrk1Δ mutant showed reduced intracellular glycerol accumulation and swollen cell morphology in response to fludioxonil, further suggesting that Hrk1 works downstream of the HOG pathway. However, Hrk1 also appeared to have Hog1-independent functions. Mutation of HRK1 not only further increased osmosensitivity of the hog1Δ mutant, but also suppressed increased azole-resistance of the hog1Δ mutant in an Erg11-independent manner. Furthermore, unlike the hog1Δ mutant, Hrk1 was not involved in capsule biosynthesis. Hrk1 was slightly involved in melanin production but dispensable for virulence of C. neoformans. These findings suggest that Hrk1 plays both Hog1-dependent and -independent roles in stress and antifungal drug susceptibility and virulence factor production in C. neoformans. Particularly, the finding that inhibition of Hrk1 substantially increases azole drug susceptibility provides a novel strategy for combination antifungal therapy.

  12. Characterization of Antifungal Activity and Nail Penetration of ME1111, a New Antifungal Agent for Topical Treatment of Onychomycosis

    OpenAIRE

    Tabata, Yuji; Takei-Masuda, Naomi; Kubota, Natsuki; Takahata, Sho; Ohyama, Makoto; Kaneda, Kaori; Iida, Maiko; Maebashi, Kazunori

    2016-01-01

    Fungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate the in vitro antifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 ...

  13. Early State Research on Antifungal Natural Products

    Directory of Open Access Journals (Sweden)

    Melyssa Negri

    2014-03-01

    Full Text Available Nosocomial infections caused by fungi have increased greatly in recent years, mainly due to the rising number of immunocompromised patients. However, the available antifungal therapeutic arsenal is limited, and the development of new drugs has been slow. Therefore, the search for alternative drugs with low resistance rates and fewer side effects remains a major challenge. Plants produce a variety of medicinal components that can inhibit pathogen growth. Studies of plant species have been conducted to evaluate the characteristics of natural drug products, including their sustainability, affordability, and antimicrobial activity. A considerable number of studies of medicinal plants and alternative compounds, such as secondary metabolites, phenolic compounds, essential oils and extracts, have been performed. Thus, this review discusses the history of the antifungal arsenal, surveys natural products with potential antifungal activity, discusses strategies to develop derivatives of natural products, and presents perspectives on the development of novel antifungal drug candidates.

  14. 2009-2013年某医院抗真菌药使用情况分析%Analysis of the Use of Antifungal Drugs in a Hospital from 2009 to 2013

    Institute of Scientific and Technical Information of China (English)

    范玉田; 王春艳

    2015-01-01

    Objective: To summarize and analyze the utilization of antifungal drugs in our hospital, so as to provide references for the rational drug use and the effective management of clinical medication.Methods:Pharmaco-economic theory was used to conduct caculations and the statistic analysis of the deifned daily dose (DDD), the amount and costs of antifungal medication, frequency of administration (DDDs), the daily cost (DUC) so on of antifungal and so on in our hospital during the years of 2009-2013.Results:The varieties, use amount and sales amount of antifungal drugs showed an increasing trend. The use intensity of nystatin tablets and imported lfuconazole injection rose steadily by year too.Conclusion:The use of antifungal drugs was basically stable in our hospital. However, there is still the need to strengthen the clinical management of antifungal drugs, reduce possible factors for fungal infections and promote rational use of drugs.%目的:对我院抗真菌药物的使用情况进行统计与分析,为临床合理用药和有效管理提供参考。方法:运用药物经济学原理,使用限定日剂量(DDD),对2009-2013年我院抗真菌药物用药数量与金额、用药频率(DDDs)、日均费用(DUC)等进行统计与分析。结果:我院抗真菌药物品种、使用数量和销售金额均呈逐年上升趋势。制霉菌素片及进口氟康唑注射液使用强度呈逐年增加趋势。结论:我院抗真菌药物的使用情况基本稳定。但仍应进一步加强抗真菌药物的临床管理,减少真菌感染的可能因素,促进药物合理应用。

  15. 2010~2012年我院深部抗真菌药使用情况分析%Analysis of deep antifungal drugs in Shidong hospital from 2010 to 2012

    Institute of Scientific and Technical Information of China (English)

    毛亚佩; 李婷; 卫英

    2014-01-01

    Objective To evaluate the utilization of deep antifungal drugs in our hospital,so as to provide evidence for the effective management of medication. Methods The defined daily dose (DDD) was used as the unit.The usage figure and consumption sum of deep antifungal drugs,DDC,DUI and AUD were analyzed in our hospital from 2010 to 2012. Results The kinds, usage figure and consumption sum of deep antifungal drugs were increasing over the 3 years.The consumption sum of Fluconazole was accounted for more than 70% of all deep antifungal drugs in three years.And the antibiotics use densities (AUD) of deep antifungal drugs presented clearly growing trend. Conclusion In order to promote the rational use of deep antifungal drugs,the causes should be further analyzed.%目的:对我院深部抗真菌药物的使用情况进行统计与评价,为临床合理用药和有效管理提供参考。方法使用限定日剂量(DDD)作为分析单位,计算累积DDDs,并以此为基础对2010~2012年我院(二级甲等)住院患者的深部抗真菌药物用药数量与金额、日均费用(DDC)、药物利用指数(DUI)、药物使用强度(AUD)进行统计计算。结果我院深部抗真菌药品种、使用数量和销售金额均呈逐年上升趋势。氟康唑是治疗深部真菌感染的主要药品。深部抗真菌药的用药强度逐年增长趋势明显。结论为促进抗菌药物合理应用,需进一步分析原因,加强监控。

  16. Lenghty reverse poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) polymeric micelles and gels for sustained release of antifungal drugs.

    Science.gov (United States)

    Figueroa-Ochoa, Edgar B; Villar-Alvarez, Eva M; Cambón, Adriana; Mistry, Dharmista; Llovo, José; Attwood, David; Barbosa, Silvia; Soltero, J F Armando; Taboada, Pablo

    2016-08-20

    In this work, we present a detailed study of the potential application of polymeric micelles and gels of four different reverse triblock poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) copolymers (BOnEOmBOn, where n denotes the respective block lengths), specifically BO8EO90BO8, BO14EO378BO14, BO20EO411BO20 and BO21EO385BO21, as effective drug transport nanocarriers. In particular, we tested the use of this kind of polymeric nanostructures as reservoirs for the sustained delivery of the antifungals griseofulvin and fluconazole for oral and topical administration. Polymeric micelles and gels formed by these copolymers were shown to solubilize important amounts of these two drugs and to have a good stability in physiologically relevant conditions for oral or topical administration. These polymeric micellar nanocarriers were able to release drugs in a sustained manner, being the release rate slower as the copolymer chain hydrophobicity increased. Different sustained drug release profiles were observed depending on the medium conditions. Gel nanocarriers were shown to display longer sustained release rates than micellar formulations, with the existence of a pulsatile-like release mode under certain solution conditions as a result of their inner network structure. Certain bioadhesive properties were observed for the polymeric physical gels, being moderately tuned by the length and hydrophobicity of the polymeric chains. Furthermore, polymeric gels and micelles showed activity against the yeast Candida albicans and the mould demartophytes (Trichophyton rubrum and Microsporum canis) and, thus, may be useful for the treatment of different cutaneous fungal infections. PMID:27289012

  17. Emerging Threats in Antifungal-Resistant Fungal Pathogens

    OpenAIRE

    Sanglard, Dominique

    2016-01-01

    The use of antifungal drugs in the therapy of fungal diseases can lead to the development of antifungal resistance. Resistance has been described for virtually all antifungal agents in diverse pathogens, including Candida and Aspergillus species. The majority of resistance mechanisms have also been elucidated at the molecular level in these pathogens. Drug resistance genes and genome mutations have been identified. Therapeutic choices are limited for the control of fungal diseases, and it is ...

  18. Natural and synthetic peptides with antifungal activity.

    Science.gov (United States)

    Ciociola, Tecla; Giovati, Laura; Conti, Stefania; Magliani, Walter; Santinoli, Claudia; Polonelli, Luciano

    2016-08-01

    In recent years, the increase of invasive fungal infections and the emergence of antifungal resistance stressed the need for new antifungal drugs. Peptides have shown to be good candidates for the development of alternative antimicrobial agents through high-throughput screening, and subsequent optimization according to a rational approach. This review presents a brief overview on antifungal natural peptides of different sources (animals, plants, micro-organisms), peptide fragments derived by proteolytic cleavage of precursor physiological proteins (cryptides), synthetic unnatural peptides and peptide derivatives. Antifungal peptides are schematically reported based on their structure, antifungal spectrum and reported effects. Natural or synthetic peptides and their modified derivatives may represent the basis for new compounds active against fungal infections. PMID:27502155

  19. Synthesis of Antifungal Drug Amorolfine Hydrochloride%抗真菌药盐酸阿莫罗芬的合成研究

    Institute of Scientific and Technical Information of China (English)

    王兴旺; 张珩; 杨艺虹; 张秀兰; 曾威

    2012-01-01

    Antifungal drug amorolfine hydrochloride was synthesized starting from formaldehyde and propanal via the processes of Mannich reaction, Friedel -Crafts reaction, saponification, condensation, reduction and salification. The affecting factors including the ratio of the raw materials, the reaction time, the reaction temperature and the catalyst were investigated. The product was prepared in an overall yield of 30.97%, and the structure was confirmed with IR, GC-MS and 'H NMR.%以甲醛和丙醛为原料,经Mannich反应、Friedel-Crafts烷基化、Saponification反应、缩合、还原、成盐反应合成抗真菌药盐酸阿莫罗芬.对影响收率的原料配比、反应时间、反应温度和催化剂等因素进行了工艺优化.通过IR、GC-MS、1H NMR确证了盐酸阿莫罗芬结构.其工艺简单、原料易得、条件温和、操作简便,总收率达30.97%(以丙醛计),具有工业化应用前景.

  20. Marketed Drugs Can Inhibit Cytochrome P450 27A1, a Potential New Target for Breast Cancer Adjuvant Therapy.

    Science.gov (United States)

    Mast, Natalia; Lin, Joseph B; Pikuleva, Irina A

    2015-09-01

    Cytochrome P450 CYP27A1 is the only enzyme in humans converting cholesterol to 27-hydroxycholesterol, an oxysterol of multiple functions, including tissue-specific modulation of estrogen and liver X receptors. Both receptors seem to mediate adverse effects of 27-hydroxycholesterol in breast cancer when the levels of this oxysterol are elevated. The present work assessed druggability of CYP27A1 as a potential antibreast cancer target. We selected 26 anticancer and noncancer medications, most approved by the Food and Drug Administration, and evaluated them first in vitro for inhibition of purified recombinant CYP27A1 and binding to the enzyme active site. Six strong CYP27A1 inhibitors/binders were identified. These were the two antibreast cancer pharmaceuticals anastrozole and fadrozole, antiprostate cancer drug bicalutamide, sedative dexmedetomidine, and two antifungals ravuconazole and posaconazole. Anastrozole was then tested in vivo on mice, which received subcutaneous drug injections for 1 week. Mouse plasma and hepatic 27-hydroxycholesterol levels were decreased 2.6- and 1.6-fold, respectively, whereas plasma and hepatic cholesterol content remained unchanged. Thus, pharmacologic CYP27A1 inhibition is possible in the whole body and individual organs, but does not negatively affect cholesterol elimination. Our results enhance the potential of CYP27A1 as an antibreast cancer target, could be of importance for the interpretation of Femara versus Anastrozole Clinical Evaluation Trial, and bring attention to posaconazole as a potential complementary anti-breast cancer medication. More medications on the US market may have unanticipated off-target inhibition of CYP27A1, and we propose strategies for their identification.

  1. Structure-Functional Characterization of Cytochrome P450 Sterol 14α-Demethylase (CYP51B) from Aspergillus fumigatus and Molecular Basis for the Development of Antifungal Drugs.

    Science.gov (United States)

    Hargrove, Tatiana Y; Wawrzak, Zdzislaw; Lamb, David C; Guengerich, F Peter; Lepesheva, Galina I

    2015-09-25

    Aspergillus fumigatus is the opportunistic fungal pathogen that predominantly affects the immunocompromised population and causes 600,000 deaths/year. The cytochrome P450 51 (CYP51) inhibitor voriconazole is currently the drug of choice, yet the treatment efficiency remains low, calling for rational development of more efficient agents. A. fumigatus has two CYP51 genes, CYP51A and CYP51B, which share 59% amino acid sequence identity. CYP51B is expressed constitutively, whereas gene CYP51A is reported to be inducible. We expressed, purified, and characterized A. fumigatus CYP51B, including determination of its substrate preferences, catalytic parameters, inhibition, and x-ray structure in complexes with voriconazole and the experimental inhibitor (R)-N-(1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide (VNI). The enzyme demethylated its natural substrate eburicol and the plant CYP51 substrate obtusifoliol at steady-state rates of 17 and 16 min(-1), respectively, but did not metabolize lanosterol, and the topical antifungal drug miconazole was the strongest inhibitor that we identified. The x-ray crystal structures displayed high overall similarity of A. fumigatus CYP51B to CYP51 orthologs from other biological kingdoms but revealed phylum-specific differences relevant to enzyme catalysis and inhibition. The complex with voriconazole provides an explanation for the potency of this relatively small molecule, whereas the complex with VNI outlines a direction for further enhancement of the efficiency of this new inhibitory scaffold to treat humans afflicted with filamentous fungal infections. PMID:26269599

  2. Retrospective Comparison of Posaconazole Levels in Patients Taking the Delayed-Release Tablet versus the Oral Suspension.

    Science.gov (United States)

    Durani, Urshila; Tosh, Pritish K; Barreto, Jason N; Estes, Lynn L; Jannetto, Paul J; Tande, Aaron J

    2015-08-01

    While posaconazole prophylaxis decreases the risk of invasive fungal infection compared to fluconazole, low bioavailability of the oral-suspension formulation limits its efficacy. A new delayed-release tablet formulation demonstrated an improved pharmacokinetic profile in healthy volunteers. However, serum levels for the two formulations have not been compared in clinical practice. This study compared achievement of therapeutic posaconazole levels in patients taking the delayed-release tablet to those taking the oral suspension. This retrospective cohort study included 93 patients initiated on posaconazole between 2012 and 2014 and had at least one serum posaconazole level measured. The primary measure was the proportion of patients achieving an initial therapeutic level (>700 ng/ml). An initial therapeutic posaconazole level was seen in 29 of 32 (91%) patients receiving tablets and 37 of 61 (61%) patients receiving suspension (P = 0.003). Among patients with a steady-state level measured 5 to 14 days after initiation, a therapeutic level was observed in 18 of 20 (90%) patients receiving tablets and 25 of 43 (58%) patients receiving suspension (P = 0.01). In these patients, the median posaconazole level of the tablet cohort (1655 ng/ml) was twice that of the suspension cohort (798 ng/ml) (P = 0.004). In this cohort study, the improved bioavailability of delayed-release posaconazole tablets translates into a significantly higher proportion of patients achieving therapeutic serum levels than in the cohort receiving the oral suspension. The results of this study strongly support the use of delayed-release tablets over suspension in patients at risk for invasive fungal infection.

  3. Attributable hospital cost and antifungal treatment of invasive fungal diseases in high-risk hematology patients: an economic modeling approach.

    Science.gov (United States)

    Ananda-Rajah, Michelle R; Cheng, Allen; Morrissey, C Orla; Spelman, Tim; Dooley, Michael; Neville, A Munro; Slavin, Monica

    2011-05-01

    Studies using patient-level data to determine the attributable cost of invasive fungal diseases (IFDs) are few. Using a case-control study with activity-based costing of patients admitted to a quaternary hospital from 2002 to 2007, we determined attributable hospitalization cost (and 12 weeks thereafter), length of stay (LOS), and costly antifungal treatment (C-AT; liposomal amphotericin B, voriconazole, posaconazole, caspofungin), expressed as defined daily doses (DDDs) per IFD episode, in patients with hematological malignancies and hematopoietic stem cell recipients. Matching criteria and median regression modeling controlled for confounding variables, including LOS prior to IFD onset. Multiple mycoses were identified in 43 matched case-control pairs (n=86). A separate sensitivity analysis included 22 unmatched patients. IFD status was associated with a median excess cost of AU$30,957 (95% confidence interval [CI]=AU$2,368 to AU$59,546; P=0.034), approximating at purchasing power parity US$21,203 (95% CI=US$1,622 to US$40,784) and €15,788 (95% CI=€1,208 to €30,368), increasing to AU$80,291 (95% CI=AU$33,636 to AU$126,946; P=0.001), i.e., US$54,993 (95% CI=US$23,038 to US$86,948) and €40,948 (95% CI=€17,154 to €64,742), with intensive care unit (ICU) requirement. Cost determinants were pharmacy costs (64%; Pcosts (27%; P=0.091), with proportions persisting through 12 weeks for 25 surviving matched pairs (pharmacy, 60% [P=0.12]; ward, 31% [P=0.21]). Median LOS was not significantly increased unless unmatched patients were included (8 days, 95% CI=1.8 to 14 days; P=0.012). Excess C-ATs were 17 DDDs (95% CI=15 to 19 DDDs; Pcase patient and 19 DDDs (95% CI=16 to 22 DDDs; Pcost, AU$29,441, 95% CI=AU$5,571 to AU$53,310, P=0.016; for C-AT, 17 DDDs, 95% CI=16 to 18 DDDs, Pcosts, with pharmacy costs, including antifungal treatment, being major determinants. Consumption of costly antifungal drugs may be a novel resource metric with wider generalizability than

  4. Susceptibilidad "in vitro" de cepas de Cryptococcus a 5 drogas antifungicas "In vitro" susceptibility of Cryptococcus strains to 5 antifungal drugs

    Directory of Open Access Journals (Sweden)

    A. J. Bava

    1989-10-01

    Full Text Available Se estudió la susceptibilidad "in vitro" de 24 cepas de 3 especies del género Cryptococcus a 5 drogas antifúngicas (anfotericina B, 5 fluorocitosina, ketoconazol, itraconazol y miconazol. Las mismas se agruparon según su especie, variedad y origen de aislamiento. Para determinar la concentración inhibitoria mínima (C.I.M. de cada droga se empleó el método de dilución en agar con el medio básico nitrogenado para levaduras, adicionado de glucosa. Se obtuvo además la media geométrica de estos valores para cada grupo y se comparó cada uno de ellos. Los resultados obtenidos fueron homogéneos con la sola excepción de las cepas de Cryptococcus sp (no neoformans, en las cuales se detectaron elevados valores de C.I.M. para la 5 fluorocitosina.A comparative study of the "in vitro" susceptibility of 24 Cryptococcus strains to 5 antifungal drugs (amphotericin B, 5 fluorocytosine, miconazole, itraconazole and ketoconazole, was carried out. These strains were grouped according to species, varieties and isolation's origins. The minimum inhibitory concentration (M.I.C. was determinated by the agar dilution technique in yeast nitrogen base agar with dextrose. The mean geometrical of the M.I.C. values of each group was compared with the others. The results obtained were homogeneous with the only exception of the "non neoformans" strains, in which, higher M.I.C. to 5 fluorocytosine values were detected.

  5. Cinnamaldehyde and its derivatives, a novel class of antifungal agents.

    Science.gov (United States)

    Shreaz, Sheikh; Wani, Waseem A; Behbehani, Jawad M; Raja, Vaseem; Irshad, Md; Karched, Maribasappa; Ali, Intzar; Siddiqi, Weqar A; Hun, Lee Ting

    2016-07-01

    The last few decades have seen an alarming rise in fungal infections, which currently represent a global health threat. Despite extensive research towards the development of new antifungal agents, only a limited number of antifungal drugs are available in the market. The routinely used polyene agents and many azole antifungals are associated with some common side effects such as severe hepatotoxicity and nephrotoxicity. Also, antifungal resistance continues to grow and evolve and complicate patient management, despite the introduction of new antifungal agents. This suitation requires continuous attention. Cinnamaldehyde has been reported to inhibit bacteria, yeasts, and filamentous molds via the inhibition of ATPases, cell wall biosynthesis, and alteration of membrane structure and integrity. In this regard, several novel cinnamaldehyde derivatives were synthesized with the claim of potential antifungal activities. The present article describes antifungal properties of cinnamaldehyde and its derivatives against diverse classes of pathogenic fungi. This review will provide an overview of what is currently known about the primary mode of action of cinnamaldehyde. Synergistic approaches for boosting the effectiveness of cinnamaldehyde and its derivatives have been highlighted. Also, a keen analysis of the pharmacologically active systems derived from cinnamaldehyde has been discussed. Finally, efforts were made to outline the future perspectives of cinnamaldehyde-based antifungal agents. The purpose of this review is to provide an overview of current knowledge about the antifungal properties and antifungal mode of action of cinnamaldehyde and its derivatives and to identify research avenues that can facilitate implementation of cinnamaldehyde as a natural antifungal. PMID:27259370

  6. Defensins: antifungal lessons from eukaryotes

    Directory of Open Access Journals (Sweden)

    Patrícia M. Silva

    2014-03-01

    Full Text Available Over the last years, antimicrobial peptides (AMPs have been the focus of intense research towards the finding of a viable alternative to current antifungal drugs. Defensins are one of the major families of AMPs and the most represented among all eukaryotic groups, providing an important first line of host defense against pathogenic microorganisms. Several of these cysteine-stabilized peptides present a relevant effect against fungi. Defensins are the AMPs with the broader distribution across all eukaryotic kingdoms, namely, Fungi, Plantæ and Animalia, and were recently shown to have an ancestor in a bacterial organism. As a part of the host defense, defensins act as an important vehicle of information between innate and adaptive immune system and have a role in immunomodulation. This multidimensionality represents a powerful host shield, hard for microorganisms to overcome using single approach resistance strategies. Pathogenic fungi resistance to conventional antimycotic drugs is becoming a major problem. Defensins, as other AMPs, have shown to be an effective alternative to the current antimycotic therapies, demonstrating potential as novel therapeutic agents or drug leads. In this review, we summarize the current knowledge on some eukaryotic defensins with antifungal action. An overview of the main targets in the fungal cell and the mechanism of action of these AMPs (namely, the selectivity for some fungal membrane components are presented. Additionally, recent works on antifungal defensins structure, activity and citotoxicity are also reviewed.

  7. 2012-2014年南京地区34家医院抗真菌药物的使用情况分析%Analysis on utilization of antifungal drugs in 34 hospitals from Nanjing area during 2012 - 2014

    Institute of Scientific and Technical Information of China (English)

    储晓媚; 罗璨

    2016-01-01

    目的:了解南京地区34家医院2012—2014年抗真菌药物的使用情况和趋势,为临床合理用药提供参考。方法收集2012—2014年南京地区34家医院抗真菌药物的使用数据,对抗真菌药物的销售金额、用药频度(DDDs)等进行统计分析。结果2012—2014年南京地区34家医院抗真菌药物的总销售金额及构成比逐年上升。深部抗真菌药的用药金额远大于浅部抗真菌药,其中三唑类用药金额最大,其次是棘白菌素类。抗真菌药金额排序中三唑类药物排在前列,伏立康唑和氟康唑稳居第1、2位。浅表抗真菌药以特比萘芬为主,销售金额逐年下降。抗真菌药的DDDs排序中,深部抗真菌药中三唑类伊曲康唑排在前列,浅部抗真菌药克霉唑、硝呋太尔制霉素排名也居于前列。结论南京地区医院2012—2014年抗真菌药物的用药金额呈增长趋势,应加强对抗真菌药物的临床应用评价工作,从而促进抗真菌药的临床合理应用。%Objective To investigate the use and trend of antifungal drugs in 34 hospitals from Nanjing area during 2012 — 2014, and to provide reference for reasonable application of antifungal drugs.Methods The data of antifungal drugs in 34 hospitals from Nanjing area during 2012 — 2014 were collected, sales amount, consumption sum, and the frequency of drug use (DDDs) were analyzed statistically.Results The total consumption sum and constituent ratio of antifungal drugs in 34 hospitals from Nanjing area during 2012 — 2014 increased yearly. Consumption sum of deep antifungal drugs were more than those of superficial antifungal drugs. The consumption sum of triazoles was the largest, and the next were echinocandins. In the consumption sum sequence of antifungal drugs, voriconazole and fluconazole in triazoles ranked the first and second. Superficial antifungal drugs were mainly consisted of terbinafine, while the consumption sum of that

  8. 2012-2014年南京地区34家医院抗真菌药物的使用情况分析%Analysis on utilization of antifungal drugs in 34 hospitals from Nanjing area during 2012 - 2014

    Institute of Scientific and Technical Information of China (English)

    储晓媚; 罗璨

    2016-01-01

    Objective To investigate the use and trend of antifungal drugs in 34 hospitals from Nanjing area during 2012 — 2014, and to provide reference for reasonable application of antifungal drugs.Methods The data of antifungal drugs in 34 hospitals from Nanjing area during 2012 — 2014 were collected, sales amount, consumption sum, and the frequency of drug use (DDDs) were analyzed statistically.Results The total consumption sum and constituent ratio of antifungal drugs in 34 hospitals from Nanjing area during 2012 — 2014 increased yearly. Consumption sum of deep antifungal drugs were more than those of superficial antifungal drugs. The consumption sum of triazoles was the largest, and the next were echinocandins. In the consumption sum sequence of antifungal drugs, voriconazole and fluconazole in triazoles ranked the first and second. Superficial antifungal drugs were mainly consisted of terbinafine, while the consumption sum of that decreased yearly. In DDDs sequence of antifungal drugs, itraconazole in triazoles of antifungal drugs was ranked the first. In superficial antifungal drugs, clotrimazole and nifuratel nysfungin ranked the top. Conclusion The consumption sum of hospitals from Nanjing area has a tendency to increase. Therefore, clinical evaluation of antifungal drugs should be strengthened, and to promote reasonable application of antifungal drugs in clinic.%目的:了解南京地区34家医院2012—2014年抗真菌药物的使用情况和趋势,为临床合理用药提供参考。方法收集2012—2014年南京地区34家医院抗真菌药物的使用数据,对抗真菌药物的销售金额、用药频度(DDDs)等进行统计分析。结果2012—2014年南京地区34家医院抗真菌药物的总销售金额及构成比逐年上升。深部抗真菌药的用药金额远大于浅部抗真菌药,其中三唑类用药金额最大,其次是棘白菌素类。抗真菌药金额排序中三唑类药物排在前列,伏

  9. Antifungals of acromyrmex, allomerus, and tetraponera ant- and cultivarassociated bacteria

    OpenAIRE

    Barke, Joerg

    2013-01-01

    The central purpose of this thesis is to test the utility of ant-microbe associations for discovering antifungal compounds with novel molecular (sub-) structures. Novel antifungals displaying reduced adverse side-effects, increased water-solubilities, and/or strong fungicidal properties would be helpful in medical science for responding to the rising prevalence of human mycoses and for solving problems with adverse side-effects in currently used antifungal drugs. Host-symbiont systems m...

  10. Survey on drug resistance of Candida to common antifungal drugs%念珠菌对临床常用抗真菌药物的耐药性分析

    Institute of Scientific and Technical Information of China (English)

    张丽君; 王博

    2012-01-01

    Objective To study the drug resistance of Candida to commonly used antifungal drugs and to survey the distribution of Candida infection in this area. Methods By using Candida color culture medium for cultivation and identification of Candida, and K - B method was used for drug sensitivity testing. Results The specimens from respiratory tract of 267 cases of Candida infection accounted for 70. 8% , urine specimens accounted for 16.9% , pus specimens for 6. 4% , pleural effusion and ascites for 3. 4% , cerebrospinal fluid for 0.7% and blood samples for 1.9%. Among species distribution, Candida albicans accounted for 61. 4% , Candida tropicalis accounted for 10. 9% , Candida krusei accounted for 6.4%, Candida glabrata accounted for 8. 6% , and other species of Candida accounted for 12.7% . The rate of resistance was 1. 1 % to ampho-tericinB, 13.1% to 5 - fluorocytosine, 46. 4% to itraconazole, 48. 3% to fluconazole and 34. 8% to ketoconazole. Conclusion The incidence of infection with Candida is in rising tendency, distribution of species and manifestations in drug resistance are different, hence clinical medication should be based on drug sensitivity test for rational application of antifungal drugs.%目的 研究本地区念珠菌感染构成及对临床常用抗真菌药物的耐药情况.方法 使用念珠菌显色培养基对念珠菌进行培养鉴定,并用现行纸片扩散法(K-B法)进行药敏实验.结果 267例念珠菌感染中呼吸道标本占70.8%、尿液占16.9%,脓液6.4%,胸腹水3.4%,脑脊液0.7%,血液1.9%;菌种分布分别为白色念珠菌占61.4%,热带念珠菌占10.9%,克柔念珠菌占6.4%,光滑念珠菌占8.6%,其他念珠菌占12.7%;耐药情况分别为两性霉素B耐药性1.1%,5-氟胞嘧啶13.1%,依曲康唑46.4%,氟康唑48.3%,酮康唑34.8%.结论 念珠菌的感染呈上升态势,菌种分布及耐药性表现均不同,临床上应根据药敏实验合理使用抗真菌药物.

  11. Exploring the Molecular Basis of Antifungal Synergies Using Genome-Wide Approaches

    OpenAIRE

    Agarwal, Ameeta K.; Tripathi, Siddharth K.; Xu, Tao; Jacob, Melissa R.; Li, Xing-Cong; Clark, Alice M.

    2012-01-01

    Drug resistance poses a significant challenge in antifungal therapy since resistance has been found for all known classes of antifungal drugs. The discovery of compounds that can act synergistically with antifungal drugs is an important strategy to overcome resistance. For such combination therapies to be effective, it is critical to understand the molecular basis for the synergism by examining the cellular effects exerted by the combined drugs. Genomic profiling technologies developed in the...

  12. Rapid determination of antifungal activity by flow cytometry.

    OpenAIRE

    Green, L.; Petersen, B.; Steimel, L; Haeber, P; Current, W

    1994-01-01

    We have developed a rapid assay of antifungal activity which utilizes flow cytometry to detect accumulation of a vital dye in drug-damaged fungal cells. Results of these studies suggest that flow cytometry may provide an improved, rapid method for determining and comparing the antifungal activities of compounds with differing modes of action.

  13. Advancements in Topical Antifungal Vehicles.

    Science.gov (United States)

    Kircik, Leon H

    2016-02-01

    The primary treatment for superficial fungal infections is antifungal topical formulations, and allylamines and azoles represent the two major classes of topical formulations that are used to treat these infections. The stratum corneum (SC) is composed of keratinocytes that are surrounded by a matrix of lipids. The efficacy of topically applied formulations depends on their ability to penetrate this lipid matrix, and the vehicle plays an integral role in the penetration of active molecule into skin. There are several challenges to formulating topical drugs, which include the biotransformation of the active molecules as they pass through the SC and the physical changes that occur to the vehicle itself when it is applied to the skin. This article will review current and emerging topical antifungal vehicles. PMID:26885798

  14. Molecular characterisation and antifungal susceptibility of clinical Trichosporon isolates in India.

    Science.gov (United States)

    Rastogi, Vijaylatha; Honnavar, Prasanna; Rudramurthy, Shivaprakash M; Pamidi, Umabala; Ghosh, Anup; Chakrabarti, Arunaloke

    2016-08-01

    In Asian countries, Trichosporon infection is a well-known disease in Japan. In India, the infection is increasingly recognised. The study was conducted to characterise the clinical Trichosporon isolates from India by phenotypic and molecular techniques. A total of 31 Trichosporon clinical isolates, recovered from patients of 14 hospitals across India were sequenced (ITS and IGS1 regions of rDNA). In vitro drug susceptibility testing of the isolates was performed against amphotericin-B, fluconazole, itraconazole, voriconazole and posaconazole. IGS1, rather than ITS sequences, correctly identified the isolates: Trichosporon asahii, 20; Trichosporon ovoides, 3; Trichosporon inkin, 2; Trichosporon asteroides, 1; Trichosporon mucoides, 1; Trichosporon loubieri, 1; Trichosporon debeurmannianum, 1; and Trichosporon dermatis, 1. Trichosporon asahii genotype III was the most common type, followed by genotype I and VII. Both these targets did not help to identify one Trichosporon to the species level. Trichosporon debeurmannianum, T. dermatis and T. asteroides were isolated for the first time from a human disease in India. The minimum inhibitory concentrations for voriconazole and posaconazole were within effective range. The study highlights the presence of wide range of Trichosporon species causing infection in India. Voriconazole or posaconazole may be the better drugs to treat such patients. PMID:27144725

  15. Economic evaluation of posaconazole versus fluconazole prophylaxis in patients with graft-versus-host disease (GVHD) in the Netherlands

    NARCIS (Netherlands)

    J.P. Jansen (Jeroen); A.K. O'Sullivan (Amy); P.J. Lugtenburg (Pieternella); L.F.R. Span (Lambert); J.J.W.M. Janssen (Jeroen); W.B. Stam (Wiro)

    2010-01-01

    textabstractThe objective of this study was to evaluate the cost-effectiveness of posaconazole versus fluconazole for the prevention of invasive fungal infections (IFI) in graft-versus-host disease (GVHD) patients in the Netherlands. A decision analytic model was developed based on a double-blind ra

  16. Economic evaluation of posaconazole versus fluconazole prophylaxis in patients with graft-versus-host disease (GVHD) in the Netherlands

    NARCIS (Netherlands)

    Jansen, Jeroen P.; O'Sullivan, Amy K.; Lugtenburg, Elly; Span, Lambert F. R.; Janssen, Jeroen J. W. M.; Stam, Wiro B.

    2010-01-01

    The objective of this study was to evaluate the cost-effectiveness of posaconazole versus fluconazole for the prevention of invasive fungal infections (IFI) in graft-versus-host disease (GVHD) patients in the Netherlands. A decision analytic model was developed based on a double-blind randomized tri

  17. Nosocomial Candidiasis: Antifungal Stewardship and the Importance of Rapid Diagnosis.

    Science.gov (United States)

    Pfaller, Michael A; Castanheira, Mariana

    2016-01-01

    Candidemia and other forms of candidiasis are associated with considerable excess mortality and costs. Despite the addition of several new antifungal agents with improved spectrum and potency, the frequency of Candida infection and associated mortality have not decreased in the past two decades. The lack of rapid and sensitive diagnostic tests has led to considerable overuse of antifungal agents resulting in increased costs, selection pressure for resistance, unnecessary drug toxicity, and adverse drug interactions. Both the lack of timely diagnostic tests and emergence of antifungal resistance pose considerable problems for antifungal stewardship. Whereas antifungal stewardship with a focus on nosocomial candidiasis should be able to improve the administration of antifungal therapy in terms of drug selection, proper dose and duration, source control and de-escalation therapy, an important parameter, timeliness of antifungal therapy, remains a victim of slow and insensitive diagnostic tests. Fortunately, new proteomic and molecular diagnostic tools are improving the time to species identification and detection. In this review we will describe the potential impact that rapid diagnostic testing and antifungal stewardship can have on the management of nosocomial candidiasis.

  18. Veronaea botryosa: molecular identification with amplified fragment length polymorphism (AFLP) and in vitro antifungal susceptibility.

    Science.gov (United States)

    Badali, Hamid; Yazdanparast, Seyed Amir; Bonifaz, Alexandro; Mousavi, Bita; de Hoog, G Sybren; Klaassen, Corné H W; Meis, Jacques F

    2013-06-01

    Inter- and intraspecific genomic variability of 18 isolates of Veronaea botryosa originating from clinical and environmental sources was studied using amplified fragment length polymorphism (AFLP). The species was originally described from the environment, but several severe cases of disseminated infection in apparently healthy individuals have been reported worldwide. All tested strains of V. botryosa, identified on the basis of sequencing and phenotypic and physiological criteria prior to our study, were confirmed by AFLP analysis, yielding a clear separation of V. botryosa as a rather homogeneous group from related species. In vitro antifungal susceptibility testing resulted in MIC90s across all strains in increasing order posaconazole (0.25 μg/ml), itraconazole (1 μg/ml), voriconazole (4 μg/ml), terbinafine (4 μg/ml), caspofungin (8 μg/ml), anidulafungin (8 μg/ml), isavuconazole (16 μg/ml), amphotericin B (16 μg/ml), and fluconazole (32 μg/ml). Overall, the isolates showed a uniform pattern of low MICs of itraconazole and posaconazole, but high MICs for remaining agents. The echinocandins (caspofungin and anidulafungin) had no activity against V. botryosa. There was no statistically significant difference between susceptibilities of environmental (n = 11) and clinical (n = 7) isolates of V. botryosa (P > 0.05).

  19. Penetration of Candida Biofilms by Antifungal Agents

    OpenAIRE

    Al-Fattani, Mohammed A.; Douglas, L. Julia

    2004-01-01

    A filter disk assay was used to investigate the penetration of antifungal agents through biofilms containing single and mixed-species biofilms containing Candida. Fluconazole permeated all single-species Candida biofilms more rapidly than flucytosine. The rates of diffusion of either drug through biofilms of three strains of Candida albicans were similar. However, the rates of drug diffusion through biofilms of C. glabrata or C. krusei were faster than those through biofilms of C. parapsilosi...

  20. Early State Research on Antifungal Natural Products

    OpenAIRE

    Melyssa Negri; Tânia P. Salci; Cristiane S. Shinobu-Mesquita; Isis R. G. Capoci; Terezinha I. E. Svidzinski; Erika Seki Kioshima

    2014-01-01

    Nosocomial infections caused by fungi have increased greatly in recent years, mainly due to the rising number of immunocompromised patients. However, the available antifungal therapeutic arsenal is limited, and the development of new drugs has been slow. Therefore, the search for alternative drugs with low resistance rates and fewer side effects remains a major challenge. Plants produce a variety of medicinal components that can inhibit pathogen growth. Studies of plant species have been cond...

  1. Rhodanineacetic Acid Derivatives as Potential Drugs: Preparation, Hydrophobic Properties and Antifungal Activity of (5-Arylalkylidene-4-oxo-2-thioxo-1,3-thiazolidin-3-ylacetic Acids

    Directory of Open Access Journals (Sweden)

    Josef Jampilek

    2009-10-01

    Full Text Available Some [(5Z-(5-arylalkylidene-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acids were prepared as potential antifungal compounds. The general synthetic approach to all synthesized compounds is presented. Lipophilicity of all the discussed rhodanine-3-acetic acid derivatives was analyzed using a reversed phase high performance liquid chromatography (RP-HPLC method. The procedure was performed under isocratic conditions with methanol as an organic modifier in the mobile phase using an end-capped non-polar C18 stationary RP column. The RP-HPLC retention parameter log k (the logarithm of the capacity factor k is compared with log P values calculated in silico. All compounds were evaluated for antifungal effects against selected fungal species. Most compounds exhibited no interesting activity, and only {(5Z-[4-oxo-5-(pyridin-2- ylmethylidene-2-thioxo-1,3-thiazolidin-3-yl]}acetic acid strongly inhibited the growth of Candida tropicalis 156, Candida krusei E 28, Candida glabrata 20/I and Trichosporon asahii 1188.

  2. Synergistic combinations of antifungals and antivirulence agents to fight against Candida albicans

    DEFF Research Database (Denmark)

    Cui, Jinhui; Ren, Biao; Tong, Yaojun;

    2015-01-01

    -drug resistance, demand innovative strategies for new effective antifungal drugs. Synergistic combinations of antifungals and anti-virulence agents highlight the pragmatic strategy to reduce the development of drug resistant and potentially repurpose known antifungals, which bypass the costly and time......Candida albicans, one of the pathogenic Candida species, causes high mortality rate in immunocompromised and high-risk surgical patients. In the last decade, only one new class of antifungal drug echinocandin was applied. The increased therapy failures, such as the one caused by multi......-consuming pipeline of new drug development. Anti-virulence and synergistic combination provide new options for antifungal drug discovery by counteracting the difficulty or failure of traditional therapy for fungal infections....

  3. Antifungal compounds from cyanobacteria.

    Science.gov (United States)

    Shishido, Tânia K; Humisto, Anu; Jokela, Jouni; Liu, Liwei; Wahlsten, Matti; Tamrakar, Anisha; Fewer, David P; Permi, Perttu; Andreote, Ana P D; Fiore, Marli F; Sivonen, Kaarina

    2015-04-01

    Cyanobacteria are photosynthetic prokaryotes found in a range of environments. They are infamous for the production of toxins, as well as bioactive compounds, which exhibit anticancer, antimicrobial and protease inhibition activities. Cyanobacteria produce a broad range of antifungals belonging to structural classes, such as peptides, polyketides and alkaloids. Here, we tested cyanobacteria from a wide variety of environments for antifungal activity. The potent antifungal macrolide scytophycin was detected in Anabaena sp. HAN21/1, Anabaena cf. cylindrica PH133, Nostoc sp. HAN11/1 and Scytonema sp. HAN3/2. To our knowledge, this is the first description of Anabaena strains that produce scytophycins. We detected antifungal glycolipopeptide hassallidin production in Anabaena spp. BIR JV1 and HAN7/1 and in Nostoc spp. 6sf Calc and CENA 219. These strains were isolated from brackish and freshwater samples collected in Brazil, the Czech Republic and Finland. In addition, three cyanobacterial strains, Fischerella sp. CENA 298, Scytonema hofmanni PCC 7110 and Nostoc sp. N107.3, produced unidentified antifungal compounds that warrant further characterization. Interestingly, all of the strains shown to produce antifungal compounds in this study belong to Nostocales or Stigonematales cyanobacterial orders.

  4. Interactive effects of antifungal and antineoplastic agents on yeasts commonly prevalent in cancer patients.

    OpenAIRE

    Ghannoum, M. A.; Motawy, M S; Abu Hatab, M A; Abu Elteen, K H; Criddle, R. S.

    1989-01-01

    The effects of combinations of antifungal and antineoplastic drugs on inhibition of the growth of yeasts which commonly infect cancer patients have been analyzed. It was shown that (i) inhibitory drug combinations could be selected in which all drugs were at levels far below their individual MICs; (ii) interactive effects among antineoplastic and antifungal drugs may be very large; (iii) optimum combinations of drugs for inhibition of yeast growth depended upon both the relative and absolute ...

  5. Genotyping and In Vitro Antifungal Susceptibility Testing of Fusarium Isolates from Onychomycosis in India.

    Science.gov (United States)

    Gupta, Chhavi; Jongman, Marit; Das, Shukla; Snehaa, K; Bhattacharya, S N; Seyedmousavi, S; van Diepeningen, Anne D

    2016-08-01

    Onychomycosis refers to fungal infection of the nail and is commonly caused by dermatophytes, while yeasts and non-dermatophytic molds (NDM) are increasingly recognized as pathogens in nail infections. The present study was done to delineate molecular epidemiology of Fusarium onychomycosis in India. Five hundred nail samples of Indian patients clinically suspected of onychomycosis were subjected to direct microscopy and fungal culture. Representative Fusarium isolates were further identified to species level by multi-locus sequencing for internal transcribed spacer, translation elongation factor 1 alpha (tef1-α) and RNA polymerase II subunit (rpb2) regions (primer pairs: ITS1/ITS4, EF1/EF2, 5f2/7cr, respectively). These representative strains were also tested for in vitro antifungal susceptibility by the broth microdilution method. Members of the genus Fusarium proved to be the most common NDM responsible for onychomycosis. The Fusarium spp. responsible for onychomycosis belonged to the Fusarium solani species complex (F. keratoplasticum and F. falciforme) and Fusarium fujikuroi species complex (F. proliferatum, F. acutatum and F. sacchari). Antifungal susceptibility results indicated that amphotericin B was the most effective antifungal across all isolates (MIC ranging 0.5-2 mg/L), followed by voriconazole (MIC ranging 1-8 µg/ml). However, a large variation was shown in susceptibility to posaconazole (MIC ranging 0.5 to >16 µg/ml). To conclude, we identified different Fusarium spp. responsible for onychomycosis in India with variation within species in susceptibility to antifungal agents, showing that fusariosis requires correct and prompt diagnosis as well as antifungal susceptibility testing. PMID:27138574

  6. In vitro resistance of clinical Fusarium species to amphotericin B and voriconazole using the EUCAST antifungal susceptibility method.

    Science.gov (United States)

    Taj-Aldeen, Saad J; Salah, Husam; Al-Hatmi, Abdullah M S; Hamed, Manal; Theelen, Bart; van Diepeningen, Anne D; Boekhout, Teun; Lass-Flörl, Cornelia

    2016-08-01

    Susceptibility testing using the EUCAST-AFST method against 39 clinical Fusarium strains consecutively collected from local and invasive infections during the last 10years assessed the in vitro activities of amphotericin B (AmB) and triazole antifungal agents. In addition, the susceptibility pattern of 12 reference strains from the CBS-KNAW Fungal Biodiversity Centre (CBS) was evaluated. In particular Fusarium petroliphilum and F. solani sensu lato were involved in disseminated infections and known for treatment failure. AmB displayed the lowest MICs followed by voriconazole VRC, posaconazole (POC). Itraconazole (ITC) showed high MIC values, displaying in vitro resistance. Clinical isolates were significantly (P antifungal therapy. Resistant profiles to AmB and VRC, which are the currently recommended agents in the guidelines for treatments, and a late diagnosis may be associated with high mortality rate in immunocompromised patients. The present antifungal susceptibility profiles showed that species- and strain-specific differences in antifungal susceptibility exist within Fusarium and that susceptibility testing is important and may improve the prognosis of these infections. PMID:27312690

  7. 7-Chloroquinolin-4-yl Arylhydrazone Derivatives: Synthesis and Antifungal Activity

    Directory of Open Access Journals (Sweden)

    Auri R. Duval

    2011-01-01

    Full Text Available Fifteen 7-chloro-4-arylhydrazonequinolines have been evaluated for their in vitro antifungal activity against eight oral fungi: Candida albicans, C. parapsilosis, C. lipolytica, C. tropicalis, C. famata, C. glabrata, Rhodutorula mucilaginosa, and R. glutinis. Several compounds exhibited minimum inhibitory concentration (MIC and minimum fungicidal concentration (MFC activities comparable with the first-line drug fluconazole. These results could be considered as an important starting point for the rational design of new antifungal agents.

  8. Recent advances in topical formulation carriers of antifungal agents

    OpenAIRE

    Eman Ahmed Bseiso; Maha Nasr; Omaima Sammour; Nabaweya A Abd El Gawad

    2015-01-01

    Fungal infections are amongst the most commonly encountered diseases affecting the skin. Treatment approaches include both topical and oral antifungal agents. The topical route is generally preferred due to the possible side effects of oral medication. Advances in the field of formulation may soon render outdated conventional products such as creams, ointments and gels. Several carrier systems loaded with antifungal drugs have demonstrated promising results in the treatment of skin fungal inf...

  9. From antidiabetic to antifungal: discovery of highly potent triazole-thiazolidinedione hybrids as novel antifungal agents.

    Science.gov (United States)

    Wu, Shanchao; Zhang, Yongqiang; He, Xiaomeng; Che, Xiaoying; Wang, Shengzheng; Liu, Yang; Jiang, Yan; Liu, Na; Dong, Guoqiang; Yao, Jianzhong; Miao, Zhenyuan; Wang, Yan; Zhang, Wannian; Sheng, Chunquan

    2014-12-01

    In an attempt to discover a new generation of triazole antifungal agents, a series of triazole-thiazolidinedione hybrids were designed and synthesized by molecular hybridization of the antifungal agent fluconazole and rosiglitazone (an antidiabetic). Most of the target compounds showed good to excellent inhibitory activity against a variety of clinically important fungal pathogens. In particular, compounds (Z)-5-(2,4-dichlorobenzylidene)-3-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)thiazolidine-2,4-dione) (15 c), (Z)-3-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-5-(furan-3-ylmethylene)thiazolidine-2,4-dione (15 j), and (Z)-3-(2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl)-5-(furan-3-ylmethylene)thiazolidine-2,4-dione (15 r) were highly active against Candida albicans, with MIC80 values in the range of 0.03-0.15 μM. Moreover, compounds 15 j and 15 r were found to be effective against four fluconazole-resistant clinical isolates; these two compounds are particularly promising antifungal leads for further optimization. Molecular docking studies revealed that the hydrogen bonding interactions between thiazolidinedione and CYP51 from C. albicans are important for antifungal activity. This study also demonstrates the effectiveness of molecular hybridization in antifungal drug discovery. PMID:25196996

  10. Evaluation of antifungal combination against Cryptococcus spp.

    Science.gov (United States)

    Reichert-Lima, Franqueline; Busso-Lopes, Ariane F; Lyra, Luzia; Peron, Isabela Haddad; Taguchi, Hideaki; Mikami, Yuzuru; Kamei, Katsuiko; Moretti, Maria Luiza; Schreiber, Angelica Z

    2016-09-01

    The second cause of death among systemic mycoses, cryptococcosis treatment represents a challenge since that 5-flucytosine is not currently available in Brazil. Looking for alternatives, this study evaluated antifungal agents, alone and combined, correlating susceptibility to genotypes. Eighty Cryptococcus clinical isolates were genotyped by URA5 gene restriction fragment length polymorphism. Antifungal susceptibility was assessed following CLSI-M27A3 for amphotericin (AMB), 5-flucytosine (5FC), fluconazole (FCZ), voriconazole (VRZ), itraconazole (ITZ) and terbinafine (TRB). Drug interaction chequerboard assay evaluated: AMB + 5FC, AMB + FCZ, AMB + TRB and FCZ + TRB. Molecular typing divided isolates into 14 C. deuterogattii (VGII) and C. neoformans isolates were found to belong to genotype VNI (n = 62) and VNII (n = 4). C. neoformans VNII was significantly less susceptible than VNI (P = 0.0407) to AMB; C. deuterogattii was significantly less susceptible than VNI and VNII to VRZ (P neoformans VNI for FCZ (P = 0.0170), ITZ (P neoformans genotype VNI isolates and all combinations showed 100% of synergism against genotype VNII isolates, suggesting the relevance of cryptococcal genotyping as it is widely known that the various genotypes (now species) have significant impact in antifungal susceptibilities and clinical outcome. In difficult-to-treat cryptococcosis, terbinafine and different antifungal combinations might be alternatives to 5FC. PMID:27135278

  11. Antifungal activity of multifunctional Fe3O4-Ag nanocolloids

    International Nuclear Information System (INIS)

    In recent years, rapid increase has been observed in the population of microbes that are resistant to conventionally used antibiotics. Antifungal drug therapy is no exception and now resistance to many of the antifungal agents in use has emerged. Therefore, there is an inevitable and urgent medical need for antibiotics with novel antimicrobial mechanisms. Aspergillus glaucus is the potential cause of fatal brain infections and hypersensitivity pneumonitis in immunocompromised patients and leads to death despite aggressive multidrug antifungal therapy. In the present article, we describe the antifungal activity of multifunctional core-shell Fe3O4-Ag nanocolloids against A. glaucus isolates. Controlled experiments are also carried out with Ag nanocolloids in order to understand the role of core (Fe3O4) in the antifungal action. The minimum inhibitory concentration (MIC) of nanocolloids is determined by the micro-dilution method. MIC of A. glaucus is 2000 μg/mL. The result is quite promising and requires further investigations in order to develop a treatment methodology against this death causing fungus in immunocompromised patients. - Research Highlights: →Synthesis of Fe3O4-Ag core-shell nanocolloids. →Antifungal activity of Fe3O4-Ag nanocolloids against Aspergillus glaucus isolates. →The MIC value for A. glaucus is 2000 μg/mL. →Antifungal activity is better or comparable with most prominent antibiotics.

  12. Econazole imprinted textiles with antifungal activity.

    Science.gov (United States)

    Hossain, Mirza Akram; Lalloz, Augustine; Benhaddou, Aicha; Pagniez, Fabrice; Raymond, Martine; Le Pape, Patrice; Simard, Pierre; Théberge, Karine; Leblond, Jeanne

    2016-04-01

    In this work, we propose pharmaceutical textiles imprinted with lipid microparticles of Econazole nitrate (ECN) as a mean to improve patient compliance while maintaining drug activity. Lipid microparticles were prepared and characterized by laser diffraction (3.5±0.1μm). Using an optimized screen-printing method, microparticles were deposited on textiles, as observed by scanning electron microscopy. The drug content of textiles (97±3μg/cm(2)) was reproducible and stable up to 4months storage at 25°C/65% Relative Humidity. Imprinted textiles exhibited a thermosensitive behavior, as witnessed by a fusion temperature of 34.8°C, which enabled a larger drug release at 32°C (temperature of the skin) than at room temperature. In vitro antifungal activity of ECN textiles was compared to commercial 1% (wt/wt) ECN cream Pevaryl®. ECN textiles maintained their antifungal activity against a broad range of Candida species as well as major dermatophyte species. In vivo, ECN textiles also preserved the antifungal efficacy of ECN on cutaneous candidiasis infection in mice. Ex vivo percutaneous absorption studies demonstrated that ECN released from pharmaceutical textiles concentrated more in the upper skin layers, where the fungal infections develop, as compared to dermal absorption of Pevaryl®. Overall, these results showed that this technology is promising to develop pharmaceutical garments textiles for the treatment of superficial fungal infections. PMID:26883854

  13. In Vitro Screening of 10 Edible Thai Plants for Potential Antifungal Properties

    OpenAIRE

    Supattra Suwanmanee; Thitinan Kitisin; Natthanej Luplertlop

    2014-01-01

    Growing rates of fungal infections and increasing resistance against standard antifungal drugs can cause serious health problems. There is, therefore, increasing interest in the potential use of medicinal plants as novel antifungal agents. This study investigates the antifungal properties of crude plant extracts from ten medicinal plant species. Crude samples were extracted using the hot water extraction process. The minimum inhibitory concentrations (MIC) and diameter zone of inhibition were...

  14. Antifungal activity of diethyldithiocarbamate.

    Science.gov (United States)

    Allerberger, F; Reisinger, E C; Söldner, B; Dierich, M P

    1989-10-01

    Sodium diethyldithiocarbamate (DTC) was evaluated for its ability to combat four different species of fungi in vitro. Using a microtiter-broth-dilution method we were able to demonstrate an antifungal activity against Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus and Mucor mucedo in doses achievable by intravenous administration in man.

  15. Efficacy Coefficients Determined Using Nail Permeability and Antifungal Activity in Keratin-Containing Media Are Useful for Predicting Clinical Efficacies of Topical Drugs for Onychomycosis.

    Science.gov (United States)

    Matsuda, Yoshiki; Sugiura, Keita; Hashimoto, Takashi; Ueda, Akane; Konno, Yoshihiro; Tatsumi, Yoshiyuki

    2016-01-01

    Onychomycosis is difficult to treat topically due to the deep location of the infection under the densely keratinized nail plate. In order to obtain an in vitro index that is relevant to the clinical efficacy of topical anti-onychomycosis drugs, we profiled five topical drugs: amorolfine, ciclopirox, efinaconazole, luliconazole, and terbinafine, for their nail permeabilities, keratin affinities, and anti-dermatophytic activities in the presence of keratin. Efinaconazole and ciclopirox permeated full-thickness human nails more deeply than luliconazole. Amorolfine and terbinafine did not show any detectable permeation. The free-drug concentration of efinaconazole in a 5% human nail keratin suspension was 24.9%, which was significantly higher than those of the other drugs (1.1-3.9%). Additionally, efinaconazole was released from human nail keratin at a greater proportion than the other drugs. The MICs of the five drugs for Trichophyton rubrum were determined at various concentrations of keratin (0-20%) in RPMI 1640 medium. The MICs of ciclopirox were not affected by keratin, whereas those of efinaconazole were slightly increased and those of luliconazole and terbinafine were markedly increased in the presence of 20% keratin. Efficacy coefficients were calculated using the nail permeation flux and MIC in media without or with keratin. Efinaconazole showed the highest efficacy coefficient, which was determined using MIC in media with keratin. The order of efficacy coefficients determined using MIC in keratin-containing media rather than keratin-free media was consistent with that of complete cure rates in previously reported clinical trials. The present study revealed that efficacy coefficients determined using MIC in keratin-containing media are useful for predicting the clinical efficacies of topical drugs. In order to be more effective, topical drugs have to possess higher efficacy coefficients. PMID:27441843

  16. Efficacy Coefficients Determined Using Nail Permeability and Antifungal Activity in Keratin-Containing Media Are Useful for Predicting Clinical Efficacies of Topical Drugs for Onychomycosis

    OpenAIRE

    Matsuda, Yoshiki; Sugiura, Keita; Hashimoto, Takashi; Ueda, Akane; Konno, Yoshihiro; TATSUMI, YOSHIYUKI

    2016-01-01

    Onychomycosis is difficult to treat topically due to the deep location of the infection under the densely keratinized nail plate. In order to obtain an in vitro index that is relevant to the clinical efficacy of topical anti-onychomycosis drugs, we profiled five topical drugs: amorolfine, ciclopirox, efinaconazole, luliconazole, and terbinafine, for their nail permeabilities, keratin affinities, and anti-dermatophytic activities in the presence of keratin. Efinaconazole and ciclopirox permeat...

  17. Efficacy Coefficients Determined Using Nail Permeability and Antifungal Activity in Keratin-Containing Media Are Useful for Predicting Clinical Efficacies of Topical Drugs for Onychomycosis.

    Science.gov (United States)

    Matsuda, Yoshiki; Sugiura, Keita; Hashimoto, Takashi; Ueda, Akane; Konno, Yoshihiro; Tatsumi, Yoshiyuki

    2016-01-01

    Onychomycosis is difficult to treat topically due to the deep location of the infection under the densely keratinized nail plate. In order to obtain an in vitro index that is relevant to the clinical efficacy of topical anti-onychomycosis drugs, we profiled five topical drugs: amorolfine, ciclopirox, efinaconazole, luliconazole, and terbinafine, for their nail permeabilities, keratin affinities, and anti-dermatophytic activities in the presence of keratin. Efinaconazole and ciclopirox permeated full-thickness human nails more deeply than luliconazole. Amorolfine and terbinafine did not show any detectable permeation. The free-drug concentration of efinaconazole in a 5% human nail keratin suspension was 24.9%, which was significantly higher than those of the other drugs (1.1-3.9%). Additionally, efinaconazole was released from human nail keratin at a greater proportion than the other drugs. The MICs of the five drugs for Trichophyton rubrum were determined at various concentrations of keratin (0-20%) in RPMI 1640 medium. The MICs of ciclopirox were not affected by keratin, whereas those of efinaconazole were slightly increased and those of luliconazole and terbinafine were markedly increased in the presence of 20% keratin. Efficacy coefficients were calculated using the nail permeation flux and MIC in media without or with keratin. Efinaconazole showed the highest efficacy coefficient, which was determined using MIC in media with keratin. The order of efficacy coefficients determined using MIC in keratin-containing media rather than keratin-free media was consistent with that of complete cure rates in previously reported clinical trials. The present study revealed that efficacy coefficients determined using MIC in keratin-containing media are useful for predicting the clinical efficacies of topical drugs. In order to be more effective, topical drugs have to possess higher efficacy coefficients.

  18. Efficacy Coefficients Determined Using Nail Permeability and Antifungal Activity in Keratin-Containing Media Are Useful for Predicting Clinical Efficacies of Topical Drugs for Onychomycosis.

    Directory of Open Access Journals (Sweden)

    Yoshiki Matsuda

    Full Text Available Onychomycosis is difficult to treat topically due to the deep location of the infection under the densely keratinized nail plate. In order to obtain an in vitro index that is relevant to the clinical efficacy of topical anti-onychomycosis drugs, we profiled five topical drugs: amorolfine, ciclopirox, efinaconazole, luliconazole, and terbinafine, for their nail permeabilities, keratin affinities, and anti-dermatophytic activities in the presence of keratin. Efinaconazole and ciclopirox permeated full-thickness human nails more deeply than luliconazole. Amorolfine and terbinafine did not show any detectable permeation. The free-drug concentration of efinaconazole in a 5% human nail keratin suspension was 24.9%, which was significantly higher than those of the other drugs (1.1-3.9%. Additionally, efinaconazole was released from human nail keratin at a greater proportion than the other drugs. The MICs of the five drugs for Trichophyton rubrum were determined at various concentrations of keratin (0-20% in RPMI 1640 medium. The MICs of ciclopirox were not affected by keratin, whereas those of efinaconazole were slightly increased and those of luliconazole and terbinafine were markedly increased in the presence of 20% keratin. Efficacy coefficients were calculated using the nail permeation flux and MIC in media without or with keratin. Efinaconazole showed the highest efficacy coefficient, which was determined using MIC in media with keratin. The order of efficacy coefficients determined using MIC in keratin-containing media rather than keratin-free media was consistent with that of complete cure rates in previously reported clinical trials. The present study revealed that efficacy coefficients determined using MIC in keratin-containing media are useful for predicting the clinical efficacies of topical drugs. In order to be more effective, topical drugs have to possess higher efficacy coefficients.

  19. Suscetibilidade a antifúngicos de cepas de Candida albicans isoladas de pacientes com estomatite protética Susceptibility to antifungal drugs of Candida albicans strains isolated from patients with denture stomatitis

    Directory of Open Access Journals (Sweden)

    Jéssica Moreira BATISTA

    1999-12-01

    Full Text Available Pacientes portadores de próteses totais, apresentam, com freqüência a chamada estomatite protética, com a qual associa-se Candida albicans determinando a chamada candidíase eritematosa. Assim, procuramos avaliar a suscetibilidade dessa levedura a agentes antifúngicos. A suscetibilidade de dezenove cepas de Candida albicans isoladas de pacientes apresentando estomatite protética foi estudada frente a: um derivado poliênico representado, pela anfotericina B (AnB, e dois derivados azóicos, cetoconazol e miconazol. A atividade antifúngica foi estudada a partir da determinação da concentração inibitória mínima (CIM e da concentração fungicida mínima (CFM, pela técnica de diluição em ágar. Os resultados obtidos, mostraram baixos valores de CIMs e CFMs (mg/ml para a AnB frente a todas as leveduras. Para o miconazol e o cetoconazol, foram observadas CIMs invariavelmente £ 4,00 mg/ml; para as CFMs, foram obtidos valores ³ 16,00 mg/ml frente a maioria das cepas. Conclui-se que a AnB apresentou maior ação fungicida in vitro enquanto os azóis demonstraram ação fungistática mas não fungicida. Acreditamos que a pesquisa de novas drogas, principalmente de uso tópico ainda é necessária, a fim de se tratar, com sucesso, a candidíase eritematosa, comumente observada nas chamadas estomatites protéticas.Users of total prosthesis present in general a high frequency of the so called denture stomatitis, associated to erythematous candidiasis. So, we evaluated the susceptibility of oral yeast to three antifungal agents. Strains of Candida albicans isolated from patients with denture stomatitis were evaluated in relation to the susceptibility of the antifungal drugs as amphotericin B (polyenic derivatives, and azole agents as ketoconazole and miconazole. The antifungal activity was evaluated, and the minimal inhibitory concentration (MIC and minimal fungicide concentration (MFC were determined utilizing the agar dilution method. The

  20. The Susceptibility Patterns of Candida Species Isolated From Urine Samples to Posaconazole and Caspofungin

    OpenAIRE

    Zarei Mahmoudabadi, Ali; REZAEI-MATEHKOLAEI, Ali; Ghanavati, Fataemeh

    2015-01-01

    Background: Candiduria is a rising condition among hospitalized patients and Candida albicans is the most common recovered agent. However, non-albicans Candida species (NACs) such as C. glabrata, C. krusei, C. parapsilosis, and C. tropicalis are also important. Although most Candida species especially C. albicans are sensitive to routinely used antifungals, an increasing trend in resistance has been observed among NACs. Objectives: The aim of the present study was to detect the susceptibility...

  1. Antifungal prophylaxis during treatment for haematological malignancies: are we there yet?

    NARCIS (Netherlands)

    Rogers, T.R.; Slavin, M.A.; Donnelly, J.P.

    2011-01-01

    Antifungal prophylaxis during treatment for haematological malignancies has been studied for 50 years, yet it has not been wholly effective even when using antifungal drugs that exhibit potent activity in vitro against a broad range of fungal pathogens. Trials have demonstrated that it can reduce th

  2. Antifungal susceptibility testing of yeast isolated from corneal infections

    Directory of Open Access Journals (Sweden)

    Mascaro Vera Lucia Degaspare Monte

    2003-01-01

    Full Text Available PURPOSE: To report the antifungal susceptibility profile of yeast isolates obtained from cases of keratitis. METHODS: Susceptibility testing of 15 yeast strains isolated from corneal infections to amphotericin B, fluconazole, itraconazole and ketoconazole was performed using the NCCLS broth microdilution assay. RESULTS: Most episodes of eye infections were caused by Candida albicans. The antifungal drugs tested showed the following minimal inhibitory concentration values against yeast isolates: 0.125-0.5 mg/ml for amphotericin B; 0.125->64.0 mg/ml for fluconazole; 0.015-1.0 mg/ml for itraconazole and 0.015-0.125 mg/ml for ketoconazole. Despite the fact that all Candida isolates were judged to be susceptible to azoles, one isolate showed a minimal inhibitory concentration value significantly higher than a 90% minimal inhibitory concentration of all tested isolates. Rhodotorula rubra was resistant to fluconazole and itraconazole. CONCLUSIONS: Despite the fact that most yeast isolates from corneal infections are usually susceptible to amphotericin B and azoles, they exhibit a wide range of minimal inhibitory concentration values for antifungal drugs. The identification of strains at species level and their susceptibility pattern to antifungal drugs should be considered before determining the concentration to be used in topical antifungal formulations in order to optimize therapeutic response in eye infections.

  3. Substitutions at Methionine 220 in the 14α-Sterol Demethylase (Cyp51A) of Aspergillus fumigatus Are Responsible for Resistance In Vitro to Azole Antifungal Drugs

    OpenAIRE

    Mellado, E.; Garcia-Effron, G.; Alcazar-Fuoli, L.; Cuenca-Estrella, M.; Rodriguez-Tudela, J. L.

    2004-01-01

    Five clinical isolates of Aspergillus fumigatus that exhibited similar patterns of reduced susceptibility to itraconazole and other triazole drugs were analyzed. Sequence analysis of genes (cyp51A and cyp51B) encoding the 14α-sterol demethylases revealed that all five strains harbored mutations in cyp51A resulting in the replacement of methionine at residue 220 by valine, lysine, or threonine. When the mutated cyp51A genes were introduced into an A. fumigatus wild-type strain, the transforman...

  4. International and multicenter comparison of EUCAST and CLSI M27-A2 broth microdilution methods for testing susceptibilities of Candida spp. to fluconazole, itraconazole, posaconazole, and voriconazole.

    NARCIS (Netherlands)

    Espinel-Ingroff, A.; Barchiesi, F.; Cuenca-Estrella, M.; Pfaller, M.A.; Rinaldi, M.; Rodriguez-Tudela, J.L.; Verweij, P.E.

    2005-01-01

    The aim of this study was to compare MICs of fluconazole, itraconazole, posaconazole, and voriconazole obtained by the European Committee on Antibiotic Susceptibility Testing (EUCAST) and CLSI (formerly NCCLS) methods in each of six centers for 15 Candida albicans (5 fluconazole-resistant and 4 susc

  5. Interaction of Common Azole Antifungals with P Glycoprotein

    Science.gov (United States)

    Wang, Er-jia; Lew, Karen; Casciano, Christopher N.; Clement, Robert P.; Johnson, William W.

    2002-01-01

    Both eucaryotic and procaryotic cells are resistant to a large number of antibiotics because of the activities of export transporters. The most studied transporter in the mammalian ATP-binding cassette transporter superfamily, P glycoprotein (P-gp), ejects many structurally unrelated amphiphilic and lipophilic xenobiotics. Observed clinical interactions and some in vitro studies suggest that azole antifungals may interact with P-gp. Such an interaction could both affect the disposition and exposure to azole antifungal therapeutics and partially explain the clinical drug interactions observed with some antifungals. Using a whole-cell assay in which the retention of a marker substrate is evaluated and quantified, we studied the abilities of the most widely prescribed orally administered azole antifungals to inhibit the function of this transporter. In a cell line presenting an overexpressed amount of the human P-gp transporter, itraconazole and ketoconazole inhibited P-gp function with 50% inhibitory concentrations (IC50s) of ∼2 and ∼6 μM, respectively. Cyclosporin A was inhibitory with an IC50 of 1.4 μM in this system. Uniquely, fluconazole had no effect in this assay, a result consistent with known clinical interactions. The effects of these azole antifungals on ATP consumption by P-gp (representing transport activity) were also assessed, and the Km values were congruent with the IC50s. Therefore, exposure of tissue to the azole antifungals may be modulated by human P-gp, and the clinical interactions of azole antifungals with other drugs may be due, in part, to inhibition of P-gp transport. PMID:11751127

  6. Antifungal therapy in European hospitals

    DEFF Research Database (Denmark)

    Zarb, P; Amadeo, B; Muller, A;

    2012-01-01

    The study aimed to identify targets for quality improvement in antifungal use in European hospitals and determine the variability of such prescribing. Hospitals that participated in the European Surveillance of Antimicrobial Consumption Point Prevalence Surveys (ESAC-PPS) were included. The WHO...... 40,878 (3.7%) antimicrobials. Antifungals were mainly (54.2%) administered orally. Hospital-acquired infections represented 44.5% of indications for antifungals followed by medical prophylaxis at 31.2%. The site of infection was not defined in 36.0% of cases but the most commonly targeted sites were...... respiratory (19.2%) and gastrointestinal (18.8%). The most used antifungal was fluconazole (60.5%) followed by caspofungin (10.5%). Antifungal-antibacterial combinations were frequently used (77.5%). The predominance of fluconazole use in participating hospitals could result in an increase in prevalence of...

  7. Case Analysis of the Participation of Clinical Pharmacist in Antifungal Drug Treatment of New Type Crypto-coccal Meningitis%临床药师参与1例新型隐球菌性脑膜炎抗真菌治疗的病例分析

    Institute of Scientific and Technical Information of China (English)

    孙闻续; 徐珽

    2015-01-01

    OBJECTIVE:To explore the method of pharmaceutical care for antifungal drug treatment of new type crypto-coccal meningitis by clinical pharmacist. METHODS:Clinical pharmacist participated in the drug treatment process for a pa-tient with new type cryptococcal meningitis. Clinical pharmacist provided pharmaceutical care in following aspects:assisting doctor to optimize antifungal drugs treatment plan,providing patients pharmaceutical monitoring and medication education, etc. During amphotericin B treatment,the patient developed refractory hypokalemia. Clinical pharmacists suggested doctors to reduce the dose of amphotericin B and additionally use voriconazole for antifungal treatment. RESULTS:The patient devel-oped refractory hypokalemia no more after the plan was adjusted. After 11 weeks of systematic antifungal treatment,the pa-tient was on the mend. CONCLUSIONS:The participation of clinical pharmacist in antifungal treatment of new type cryptococ-cal meningitis indicates that following the instructions,but not lost flexible disposal;providing service actively,and details is guarantee of safety.%目的:探讨临床药师在新型隐球菌性脑膜炎患者抗真菌治疗中的药学服务方法。方法:临床药师参与1例新型隐球菌性脑膜炎患者的药物治疗过程,从协助医师优化抗真菌药物治疗方案、对患者进行药学监护、不良反应处理及用药教育等方面提供药学服务。使用两性霉素B期间,患者出现顽固性低钾血症,临床药师建议医师降低两性霉素B剂量,加用伏立康唑抗真菌治疗。结果:调整抗真菌治疗方案后,患者未再出现低血钾;经系统抗真菌治疗11周后,患者病情较前明显好转。结论:临床药师参与新型隐球菌性脑膜炎抗真菌治疗的心得是:遵循指南,但不失灵活处理;主动服务,细节保障用药安全。

  8. [New developments in antifungal therapy: fluconazole, itraconazole, voriconazole, caspofungin

    NARCIS (Netherlands)

    Wout, J.W. van 't; Kuijper, E.J.; Verweij, P.E.; Kullberg, B.J.

    2004-01-01

    The azole antifungal voriconazole and the echinocandin caspofungin have recently become available for the treatment of invasive mycoses. Fluconazole remains the drug of choice for candidemia, except for infections with one of the resistent species such as Candida krusei and some strains of Candida g

  9. Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity

    Directory of Open Access Journals (Sweden)

    Deepa Gupta

    2015-01-01

    Full Text Available Much research has been carried out with the aim to discover the therapeutic values of chalcone derivatives. Chalcones possess wide range of pharmacological activity such as antibacterial, antimalarial, antiprotozoal, antitubercular, anticancer, and antifungal agents etc. The presence of reactive α,β-unsaturated keto group in chalcones is found to be responsible for their biological activity. The rapid developments of resistance to antifungal agents, led to design, and synthesize the new antifungal agents. The derivatives of chalcones were prepared using Claisen-Schmidt condensation scheme with appropriate tetralone and aldehyde derivatives. Ten derivatives were synthesized and were biologically screened for antifungal activity. The newly synthesized derivatives of chalcone showed antifungal activity against fungal species, Microsporum gypseum. The results so obtained were superior or comparable to ketoconazole. It was observed that none of the compounds tested showed positive results for fungi Candida albicans nor against fungi Aspergillus niger. Chalcone derivatives showed inhibitory effect against M. gypseum species of fungus. It was found that among the chalcone derivatives so synthesized, two of them, that is, 4-chloro derivative, and unsubstituted derivative of chalcone showed antifungal activity superior to ketoconazole. Thus, these can be the potential new molecule as antifungal agent.

  10. Antifungal susceptibility profiles of 1698 yeast reference strains revealing potential emerging human pathogens.

    Directory of Open Access Journals (Sweden)

    Marie Desnos-Ollivier

    Full Text Available New molecular identification techniques and the increased number of patients with various immune defects or underlying conditions lead to the emergence and/or the description of novel species of human and animal fungal opportunistic pathogens. Antifungal susceptibility provides important information for ecological, epidemiological and therapeutic issues. The aim of this study was to assess the potential risk of the various species based on their antifungal drug resistance, keeping in mind the methodological limitations. Antifungal susceptibility profiles to the five classes of antifungal drugs (polyens, azoles, echinocandins, allylamines and antimetabolites were determined for 1698 yeast reference strains belonging to 992 species (634 Ascomycetes and 358 Basidiomycetes. Interestingly, geometric mean minimum inhibitory concentrations (MICs of all antifungal drugs tested were significantly higher for Basidiomycetes compared to Ascomycetes (p<0.001. Twenty four strains belonging to 23 species of which 19 were Basidiomycetes seem to be intrinsically "resistant" to all drugs. Comparison of the antifungal susceptibility profiles of the 4240 clinical isolates and the 315 reference strains belonging to 53 shared species showed similar results. Even in the absence of demonstrated in vitro/in vivo correlation, knowing the in vitro susceptibility to systemic antifungal agents and the putative intrinsic resistance of yeast species present in the environment is important because they could become opportunistic pathogens.

  11. Recent advances in topical formulation carriers of antifungal agents.

    Science.gov (United States)

    Bseiso, Eman Ahmed; Nasr, Maha; Sammour, Omaima; Abd El Gawad, Nabaweya A

    2015-01-01

    Fungal infections are amongst the most commonly encountered diseases affecting the skin. Treatment approaches include both topical and oral antifungal agents. The topical route is generally preferred due to the possible side effects of oral medication. Advances in the field of formulation may soon render outdated conventional products such as creams, ointments and gels. Several carrier systems loaded with antifungal drugs have demonstrated promising results in the treatment of skin fungal infections. Examples of these newer carriers include micelles, lipidic systems such as solid lipid nanoparticles and nanostructured lipid carriers, microemulsions and vesicular systems such as liposomes, niosomes, transfersomes, ethosomes, and penetration enhancer vesicles. PMID:26261140

  12. Recent advances in topical formulation carriers of antifungal agents

    Directory of Open Access Journals (Sweden)

    Eman Ahmed Bseiso

    2015-01-01

    Full Text Available Fungal infections are amongst the most commonly encountered diseases affecting the skin. Treatment approaches include both topical and oral antifungal agents. The topical route is generally preferred due to the possible side effects of oral medication. Advances in the field of formulation may soon render outdated conventional products such as creams, ointments and gels. Several carrier systems loaded with antifungal drugs have demonstrated promising results in the treatment of skin fungal infections. Examples of these newer carriers include micelles, lipidic systems such as solid lipid nanoparticles and nanostructured lipid carriers, microemulsions and vesicular systems such as liposomes, niosomes, transfersomes, ethosomes, and penetration enhancer vesicles.

  13. In vitro and in vivo studies of the antiparasitic activity of sterol 14α-demethylase (CYP51) inhibitor VNI against drug-resistant strains of Trypanosoma cruzi.

    Science.gov (United States)

    Soeiro, Maria de Nazaré Correia; de Souza, Elen Mello; da Silva, Cristiane França; Batista, Denise da Gama Jaen; Batista, Marcos Meuser; Pavão, Beatriz Philot; Araújo, Julianna Siciliano; Aiub, Claudia Alessandra Fortes; da Silva, Patrícia Bernardino; Lionel, Jessica; Britto, Constança; Kim, Kwangho; Sulikowski, Gary; Hargrove, Tatiana Y; Waterman, Michael R; Lepesheva, Galina I

    2013-09-01

    Chagas disease affects more than 10 million people worldwide, and yet, as it has historically been known as a disease of the poor, it remains highly neglected. Two currently available drugs exhibit severe toxicity and low effectiveness, especially in the chronic phase, while new drug discovery has been halted for years as a result of a lack of interest from pharmaceutical companies. Although attempts to repurpose the antifungal drugs posaconazole and ravuconazole (inhibitors of fungal sterol 14α-demethylase [CYP51]) are finally in progress, development of cheaper and more efficient, preferably Trypanosoma cruzi-specific, chemotherapies would be highly advantageous. We have recently reported that the experimental T. cruzi CYP51 inhibitor VNI cures with 100% survival and 100% parasitological clearance both acute and chronic murine infections with the Tulahuen strain of T. cruzi. In this work, we further explored the potential of VNI by assaying nitro-derivative-resistant T. cruzi strains, Y and Colombiana, in highly stringent protocols of acute infection. The data show high antiparasitic efficacy of VNI and its derivative (VNI/VNF) against both forms of T. cruzi that are relevant for mammalian host infection (bloodstream and amastigotes), with the in vivo potency, at 25 mg/kg twice a day (b.i.d.), similar to that of benznidazole (100 mg/kg/day). Transmission electron microscopy and reverse mutation tests were performed to explore cellular ultrastructural and mutagenic aspects of VNI, respectively. No mutagenic potential could be seen by the Ames test at up to 3.5 μM, and the main ultrastructural damage induced by VNI in T. cruzi was related to Golgi apparatus and endoplasmic reticulum organization, with membrane blebs presenting an autophagic phenotype. Thus, these preliminary studies confirm VNI as a very promising trypanocidal drug candidate for Chagas disease therapy. PMID:23774435

  14. Molecular identification and antifungal susceptibility profiles of Candida parapsilosis complex species isolated from culture collection of clinical samples

    Directory of Open Access Journals (Sweden)

    Fábio Silvestre Ataides

    2015-08-01

    Full Text Available AbstractINTRODUCTION:Candida parapsilosis is a common yeast species found in cases of onychomycosis and candidemia associated with infected intravascular devices. In this study, we differentiated Candida parapsilosis sensu stricto, Candida orthopsilosis , and Candida metapsilosis from a culture collection containing blood and subungual scraping samples. Furthermore, we assessed the in vitro antifungal susceptibility of these species to fluconazole, itraconazole, voriconazole, posaconazole, amphotericin B, and caspofungin.METHODS:Differentiation of C. parapsilosis complex species was performed by amplification of the secondary alcohol dehydrogenase (SADH gene and digestion by the restriction enzyme Ban I. All isolates were evaluated for the determination of minimal inhibitory concentrations using Etest, a method for antifungal susceptibility testing.RESULTS:Among the 87 isolates, 78 (89.7% were identified as C. parapsilosis sensu stricto , five (5.7% were identified as C. orthopsilosis , and four (4.6% were identified as C. metapsilosis . Analysis of antifungal susceptibility showed that C. parapsilosis sensu strictoisolates were less susceptible to amphotericin B and itraconazole. One C. parapsilosis sensu stricto isolate was resistant to amphotericin B and itraconazole. Moreover, 10.2% of C. parapsilosis sensu stricto isolates were resistant to caspofungin. Two C. parapsilosis sensu strictoisolates and one C. metapsilosis isolate were susceptible to fluconazole in a dose-dependent manner.CONCLUSIONS:We reported the first molecular identification of C. parapsilosiscomplex species in State of Goiás, Brazil. Additionally, we showed that although the three species exhibited differences in antifungal susceptibility profiles, the primary susceptibility of this species was to caspofungin.

  15. Peptide-based Antifungal Therapies against Emerging Infections

    OpenAIRE

    Matejuk, A.; Leng, Q.; Begum, M.D.; Woodle, M.C.; Scaria, P.; Chou, S-T; Mixson, A. J.

    2010-01-01

    Acquired drug resistance to mycotic infections is rapidly emerging as a major medical problem. Opportunistic fungal infections create therapeutic challenges, particularly in high risk immunocompromised patients with AIDS, cancer, and those undergoing transplantation. Higher mortality and/or morbidity rates due to invasive mycosis have been increasing over the last 20 years, and in light of growing resistance to commonly used antibiotics, novel antifungal drugs and approaches are required. Cur...

  16. Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity

    OpenAIRE

    Deepa Gupta; Jain, D. K.

    2015-01-01

    Much research has been carried out with the aim to discover the therapeutic values of chalcone derivatives. Chalcones possess wide range of pharmacological activity such as antibacterial, antimalarial, antiprotozoal, antitubercular, anticancer, and antifungal agents etc. The presence of reactive α,β-unsaturated keto group in chalcones is found to be responsible for their biological activity. The rapid developments of resistance to antifungal agents, led to design, and synthesize the new antif...

  17. Characterization of Antifungal Activity and Nail Penetration of ME1111, a New Antifungal Agent for Topical Treatment of Onychomycosis.

    Science.gov (United States)

    Tabata, Yuji; Takei-Masuda, Naomi; Kubota, Natsuki; Takahata, Sho; Ohyama, Makoto; Kaneda, Kaori; Iida, Maiko; Maebashi, Kazunori

    2016-02-01

    Fungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate the in vitro antifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 showed potent antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes (the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and an MIC50 and MIC90 of 0.5 mg/liter for both. Importantly, none of the tested isolates showed an elevated ME1111 MIC. Moreover, the antifungal activity of ME1111 was minimally affected by 5% wool keratin powder in comparison to the other antifungals tested. The ME1111 solution was able to penetrate human nails and inhibit fungal growth in a dose-dependent manner according to the TurChub assay. In contrast, 8% ciclopirox and 5% amorolfine nail lacquers showed no activity under the same conditions. ME1111 demonstrated approximately 60-fold-greater selectivity in inhibition of Trichophyton spp. than of human cell lines. Our findings demonstrate that ME1111 possesses potent antidermatophyte activity, maintains this activity in the presence of keratin, and possesses excellent human nail permeability. These results suggest that ME1111 is a promising topical medication for the treatment of onychomycosis and therefore warrants further clinical evaluation. PMID:26643333

  18. Characterization of Antifungal Activity and Nail Penetration of ME1111, a New Antifungal Agent for Topical Treatment of Onychomycosis.

    Science.gov (United States)

    Tabata, Yuji; Takei-Masuda, Naomi; Kubota, Natsuki; Takahata, Sho; Ohyama, Makoto; Kaneda, Kaori; Iida, Maiko; Maebashi, Kazunori

    2016-02-01

    Fungal nail infection (onychomycosis) is a prevalent disease in many areas of the world, with a high incidence approaching 23%. Available antifungals to treat the disease suffer from a number of disadvantages, necessitating the discovery of new efficacious and safe antifungals. Here, we evaluate the in vitro antifungal activity and nail penetration ability of ME1111, a novel antifungal agent, along with comparator drugs, including ciclopirox, amorolfine, terbinafine, and itraconazole. ME1111 showed potent antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes (the major etiologic agents of onychomycosis) strains isolated in Japan and reference fungal strains with an MIC range of 0.12 to 0.5 mg/liter and an MIC50 and MIC90 of 0.5 mg/liter for both. Importantly, none of the tested isolates showed an elevated ME1111 MIC. Moreover, the antifungal activity of ME1111 was minimally affected by 5% wool keratin powder in comparison to the other antifungals tested. The ME1111 solution was able to penetrate human nails and inhibit fungal growth in a dose-dependent manner according to the TurChub assay. In contrast, 8% ciclopirox and 5% amorolfine nail lacquers showed no activity under the same conditions. ME1111 demonstrated approximately 60-fold-greater selectivity in inhibition of Trichophyton spp. than of human cell lines. Our findings demonstrate that ME1111 possesses potent antidermatophyte activity, maintains this activity in the presence of keratin, and possesses excellent human nail permeability. These results suggest that ME1111 is a promising topical medication for the treatment of onychomycosis and therefore warrants further clinical evaluation.

  19. Application of antifungal drugs in the treatment of cutaneous and mucocutaneous leishmaniasis%抗真菌药物在皮肤黏膜利什曼病治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    曲卉; 李若瑜; 余进; 王爱平

    2015-01-01

    Leishmaniasis is zoonotic disease caused byLeishmania with different clinical manifestations. It can be characterized into three clinical types: visceral leishmaniasis, mucocutaneous leishmaniasis and cutaneous leishmaniasis. Traditionally, antimony is the ifrst-line treatment for leishmaniasis, but its application is compromised due to the high adverse effects and the emergence of drug resistantLeishmania isolates. Clinical researches have shown that amphotericin B can be used in patients infected by antimony resistant isolates, and treatment of azole and propylene amine can also be effective and safe. Through the analysis of the components inLeishmania membrane, this article further illustrates the mechanism, usage and efifcacy of antifungal agents in the treatment of leishmaniasis.%利什曼病(leishmaniasis)是由利什曼原虫(Leishmania spp)引起的一组具有不同临床表现的疾病,可分为内脏利什曼病、黏膜皮肤利什曼病和皮肤利什曼病3个临床类型。利什曼病的治疗首选五价锑制剂,但因其不良反应发生率高、部分利什曼原虫对锑剂耐药,应用受到了一定的限制。临床研究显示抗真菌药物两性霉素B可以用于对锑剂耐药的患者,唑类和丙烯胺类抗真菌药物对部分利什曼病治疗有效、安全。该文从利什曼原虫胞膜成分的分析入手,重点介绍抗真菌药物在利什曼病治疗中的作用机制、用法及疗效。

  20. Searching new antifungals: The use of in vitro and in vivo methods for evaluation of natural compounds.

    Science.gov (United States)

    Scorzoni, Liliana; Sangalli-Leite, Fernanda; de Lacorte Singulani, Junya; de Paula E Silva, Ana Carolina Alves; Costa-Orlandi, Caroline Barcelos; Fusco-Almeida, Ana Marisa; Mendes-Giannini, Maria José Soares

    2016-04-01

    In the last decades, the increased number of immunocompromised patients has led to the emergence of many forms of fungal infections. Furthermore, there are a restricted arsenal of antifungals available and an increase in the development of resistance to antifungal drugs. Because of these disadvantages, the search for new antifungal agents in natural sources has increased. The development of these new antifungal drugs involves various steps and methodologies. The evaluation of the in vitro antifungal activity and cytotoxicity are the first steps in the screening. There is also the possibility of antifungal combinations to improve the therapy and reduce toxicity. Despite that, the application of the new antifungal candidate could be used in association with photodynamic therapy or using nanotechnology as an ally. In vivo tests can be performed to evaluate the efficacy and toxicity using conventional and alternative animal models. In this work, we review the methods available for the evaluation of the antifungal activity and safety of natural products, as well as the recent advances of new technology in the application of natural products for antifungal therapy. PMID:26853122

  1. Identification of Ebsulfur Analogues with Broad-Spectrum Antifungal Activity.

    Science.gov (United States)

    Ngo, Huy X; Shrestha, Sanjib K; Garneau-Tsodikova, Sylvie

    2016-07-19

    Invasive fungal infections are on the rise due to an increased population of critically ill patients as a result of HIV infections, chemotherapies, and organ transplantations. Current antifungal drugs are helpful, but are insufficient in addressing the problem of drug-resistant fungal infections. Thus, there is a growing need for novel antimycotics that are safe and effective. The ebselen scaffold has been evaluated in clinical trials and has been shown to be safe in humans. This makes ebselen an attractive scaffold for facile translation from bench to bedside. We recently reported a library of ebselen-inspired ebsulfur analogues with antibacterial properties, but their antifungal activity has not been characterized. In this study, we repurposed ebselen, ebsulfur, and 32 additional ebsulfur analogues as antifungal agents by evaluating their antifungal activity against a panel of 13 clinically relevant fungal strains. The effect of induction of reactive oxygen species (ROS) by three of these compounds was evaluated. Their hemolytic and cytotoxicity activities were also determined using mouse erythrocytes and mammalian cells. The MIC values of these compounds were found to be in the range of 0.02-12.5 μg mL(-1) against the fungal strains tested. Notably, yeast cells treated with our compounds showed an accumulation of ROS, which may further contribute to the growth-inhibitory effect against fungi. This study provides new lead compounds for the development of antimycotic agents. PMID:27334363

  2. Influence of Common Antifungal Drugs on Growth of Common Vaginal Lactobacilli%常用抗假丝酵母菌药物对阴道常见乳杆菌生长影响的研究

    Institute of Scientific and Technical Information of China (English)

    张励; 刘建华

    2012-01-01

    .0%, 60.0% and 25.0%, respectively, there was a significant difference among them (P<0.05). And the detection rate of H2O2-generating Lactobacilli in itraconazole group was significantly higher than that in miconazole group and nystatin group (p<0.05). Conclusion: Itraconazole was effective for the treatment of WC, and had relatively less influence on the growth of H2O2-generating Lactobacilli, and it can contribute to maintain vaginal normal microflora, and could be an ideal antifungal drug for WC treatment.

  3. Antifungal and antiviral products of marine organisms.

    Science.gov (United States)

    Cheung, Randy Chi Fai; Wong, Jack Ho; Pan, Wen Liang; Chan, Yau Sang; Yin, Cui Ming; Dan, Xiu Li; Wang, He Xiang; Fang, Evandro Fei; Lam, Sze Kwan; Ngai, Patrick Hung Kui; Xia, Li Xin; Liu, Fang; Ye, Xiu Yun; Zhang, Guo Qing; Liu, Qing Hong; Sha, Ou; Lin, Peng; Ki, Chan; Bekhit, Adnan A; Bekhit, Alaa El-Din; Wan, David Chi Cheong; Ye, Xiu Juan; Xia, Jiang; Ng, Tzi Bun

    2014-04-01

    Marine organisms including bacteria, fungi, algae, sponges, echinoderms, mollusks, and cephalochordates produce a variety of products with antifungal activity including bacterial chitinases, lipopeptides, and lactones; fungal (-)-sclerotiorin and peptaibols, purpurides B and C, berkedrimane B and purpuride; algal gambieric acids A and B, phlorotannins; 3,5-dibromo-2-(3,5-dibromo-2-methoxyphenoxy)phenol, spongistatin 1, eurysterols A and B, nortetillapyrone, bromotyrosine alkaloids, bis-indole alkaloid, ageloxime B and (-)-ageloxime D, haliscosamine, hamigeran G, hippolachnin A from sponges; echinoderm triterpene glycosides and alkene sulfates; molluscan kahalalide F and a 1485-Da peptide with a sequence SRSELIVHQR; and cepalochordate chitotriosidase and a 5026.9-Da antifungal peptide. The antiviral compounds from marine organisms include bacterial polysaccharide and furan-2-yl acetate; fungal macrolide, purpurester A, purpurquinone B, isoindolone derivatives, alterporriol Q, tetrahydroaltersolanol C and asperterrestide A, algal diterpenes, xylogalactofucan, alginic acid, glycolipid sulfoquinovosyldiacylglycerol, sulfated polysaccharide p-KG03, meroditerpenoids, methyl ester derivative of vatomaric acid, lectins, polysaccharides, tannins, cnidarian zoanthoxanthin alkaloids, norditerpenoid and capilloquinol; crustacean antilipopolysaccharide factors, molluscan hemocyanin; echinoderm triterpenoid glycosides; tunicate didemnin B, tamandarins A and B and; tilapia hepcidin 1-5 (TH 1-5), seabream SauMx1, SauMx2, and SauMx3, and orange-spotted grouper β-defensin. Although the mechanisms of antifungal and antiviral activities of only some of the aforementioned compounds have been elucidated, the possibility to use those known to have distinctly different mechanisms, good bioavailability, and minimal toxicity in combination therapy remains to be investigated. It is also worthwhile to test the marine antimicrobials for possible synergism with existing drugs. The prospects of

  4. Antifungal activity of the lemongrass oil and citral against Candida spp.

    Directory of Open Access Journals (Sweden)

    Cristiane de Bona da Silva

    2008-02-01

    Full Text Available Superficial mycoses of the skin are among the most common dermatological infections, and causative organisms include dermatophytic, yeasts, and non-dermatophytic filamentous fungi. The treatment is limited, for many reasons, and new drugs are necessary. Numerous essential oils have been tested for both in vitro and in vivo antifungal activity and some pose much potential as antifungal agents. By using disk diffusion assay, we evaluated the antifungal activity of lemongrass oil and citral against yeasts of Candida species (Candida albicans, C. glabrata, C. krusei, C. parapsilosis and C. tropicalis. This study showed that lemongrass oil and citral have a potent in vitro activity against Candida spp.

  5. Design,synthesis and antifungal activities in vitro of novel tetralin compounds

    Institute of Scientific and Technical Information of China (English)

    Hui Tang; You Jun Zhou; Yao Wu Li; Jia Guo Lv; Can Hui Zheng; Jun Chen; Ju Zhu

    2008-01-01

    Novel chiral tetralin compounds were designed and synthesized, and their antifungal activities in vitro were tested. The results showed that all of target compounds had potent antifungal activities, and were stronger than that of control compounds tetrahydroisoquinolines. The binding model of lead molecules in the active site of CYP51 of Candida albicans showed that lead compound specifically interacted with the amino acids residues in the active site, without binding with the heme of CYP51, which was different from azole antifungal drugs. The present study might afford a novel lead molecule to develop non-azole CYP51 inhibitors of fungi.

  6. Multidrug-Resistant Transporter Mdr1p-Mediated Uptake of a Novel Antifungal Compound

    OpenAIRE

    Sun, Nuo; Li, Dongmei; Fonzi, William; Xin LI; Zhang, Lixin; Calderone, Richard

    2013-01-01

    The activity of many anti-infectious drugs has been compromised by the evolution of multidrug-resistant (MDR) pathogens. For life-threatening fungal infections, such as those caused by Candida albicans, overexpression of MDR1, which encodes an MDR efflux pump of the major facilitator superfamily (MFS), often confers resistance to chemically unrelated substances, including the most commonly used azole antifungals. As the development of new and efficacious antifungals has lagged far behind the ...

  7. In vitro antifungal activity of 2-(2'-hydroxy-5'-aminophenyl)benzoxazole in Candida spp. strains.

    Science.gov (United States)

    Daboit, Tatiane Caroline; Stopiglia, Cheila Denise Ottonelli; Carissimi, Mariana; Corbellini, Valeriano Antonio; Stefani, Valter; Scroferneker, Maria Lúcia

    2009-11-01

    The development of azole antifungals has allowed for the treatment of several fungal infections. However, the use of these compounds is restricted because of their hepatotoxicity or because they need to be administered together with other drugs in order to prevent resistance to monotherapy. Benzoxazole derivatives are among the most thriving molecular prototypes for the development of antifungal agents. 2-(2'-hydroxyphenyl) benzoxazoles are versatile molecules that emit fluorescence and have antibacterial, antiviral and antifungal properties. 2-(2'-hydroxy-5'-aminophenyl) benzoxazole (HAMBO) was tested against Candida yeast. The inhibition provided by HAMBO was lower than that of fluconazole, showing low antifungal activity against Candida spp., but equivalent to that of benzoxazoles tested in similar studies. HAMBO showed fungistatic activity against all analysed strains. This class of novel benzoxazole compounds may be used as template to produce better antifungal drugs.

  8. Resistance to antifungals that target CYP51.

    Science.gov (United States)

    Parker, Josie E; Warrilow, Andrew G S; Price, Claire L; Mullins, Jonathan G L; Kelly, Diane E; Kelly, Steven L

    2014-10-01

    Fungal diseases are an increasing global burden. Fungi are now recognised to kill more people annually than malaria, whilst in agriculture, fungi threaten crop yields and food security. Azole resistance, mediated by several mechanisms including point mutations in the target enzyme (CYP51), is increasing through selection pressure as a result of widespread use of triazole fungicides in agriculture and triazole antifungal drugs in the clinic. Mutations similar to those seen in clinical isolates as long ago as the 1990s in Candida albicans and later in Aspergillus fumigatus have been identified in agriculturally important fungal species and also wider combinations of point mutations. Recently, evidence that mutations originate in the field and now appear in clinical infections has been suggested. This situation is likely to increase in prevalence as triazole fungicide use continues to rise. Here, we review the progress made in understanding azole resistance found amongst clinically and agriculturally important fungal species focussing on resistance mechanisms associated with CYP51. Biochemical characterisation of wild-type and mutant CYP51 enzymes through ligand binding studies and azole IC50 determinations is an important tool for understanding azole susceptibility and can be used in conjunction with microbiological methods (MIC50 values), molecular biological studies (site-directed mutagenesis) and protein modelling studies to inform future antifungal development with increased specificity for the target enzyme over the host homologue. PMID:25320648

  9. DYSREGULATION OF ION HOMEOSTASIS BY ANTIFUNGAL AGENTS

    Directory of Open Access Journals (Sweden)

    Yongqiang eZhang

    2012-04-01

    Full Text Available Ion signaling and transduction networks are central to fungal development and virulence because they regulate gene expression, filamentation, host association and invasion, pathogen stress response and survival. Dysregulation of ion homeostasis rapidly mediates cell death, forming the mechanistic basis by which a growing number of amphipathic but structurally unrelated compounds elicit antifungal activity. Included in this group is carvacrol, a terpenoid phenol that is a prominent component of oregano and other plant essential oils. Carvacrol triggers an early dose dependent Ca2+ burst and long lasting pH changes in the model yeast S. cerevisiae. The distinct phases of ionic transients and a robust transcriptional response that overlaps with Ca2+ stress and nutrient starvation point to specific signaling events elicited by plant terpenoid phenols, rather than a non-specific lesion of the membrane as was previously considered. We discuss the potential use of plant essential oils and other agents that disrupt ion signaling pathways as chemosensitizers to augment conventional antifungal therapy, and to convert fungistatic drugs with strong safety profiles into fungicides.

  10. Development of buccal adhesive tablet with prolonged antifungal activity: Optimization and ex vivo deposition studies

    Directory of Open Access Journals (Sweden)

    Madgulkar A

    2009-01-01

    Full Text Available The purpose of the present work was to prepare buccal adhesive tablets of miconazole nitrate. The simplex centroid experimental design was used to arrive at optimum ratio of carbopol 934P, hydroxypropylmethylcellulose K4M and polyvinylpyrollidone, which will provide desired drug release and mucoadhesion. Swelling index, mucoadhesive strength and in vitro drug release of the prepared tablet was determined. The drug release and bioadhesion was dependent on type and relative amounts of the polymers. The optimized combination was subjected to in vitro antifungal activity, transmucosal permeation, drug deposition in mucosa, residence time and bioadhesion studies. IR spectroscopy was used to investigate any interaction between drug and excipients. Dissolution of miconazole from tablets was sustained for 6 h. based on the results obtained, it can be concluded that the prepared slow release buccoadhesive tablets of miconazole would markedly prolong the duration of antifungal activity. Comparison of in vitro antifungal activity of tablet with marketed gel showed that drug concentrations above the minimum inhibitory concentration were achieved immediately from both formulations but release from tablet was sustained up to 6 h, while the gel showed initially fast drug release, which did not sustain later. Drug permeation across buccal mucosa was minimum from the tablet as well as marketed gel; the deposition of drug in mucosa was higher in case of tablet. In vitro residence time and bioadhesive strength of tablet was higher than gel. Thus the buccoadhesive tablet of miconazole nitrate may offer better control of antifungal activity as compared to the gel formulation.

  11. Antifungal activity of different silver nanoparticles suspensions against Candida biofilms

    OpenAIRE

    Monteiro, D. R.; Silva, Sónia Carina; Negri, M.; Camargo, E. R.; Gorup, L. F.; Takamiya, A.; Oliveira, Rosário; Barbosa, D. B.; Henriques, Mariana

    2012-01-01

    Objective: The tolerance of Candida biofilms to conventional antifungal drugs has stimulated the search for new therapies that could prevent or treat Candida-associated denture stomatitis. The objectives of this study were (i) to assess the antibiofilm activity of different silver nanoparticles (SN) suspensions against Candida albicans and Candida glabrata biofilms and (ii) to evaluate the effect of these nanoparticles on the matrix composition and the structure of Candida biofilms. Metho...

  12. Refractory invasive aspergillosis controlled with posaconazole and pulmonary surgery in a patient with chronic granulomatous disease: case report

    OpenAIRE

    Kepenekli, Eda; Soysal, Ahmet; Kuzdan, Canan; Ermerak, Nezih Onur; Yüksel, Mustafa; Bakır, Mustafa

    2014-01-01

    Invasive aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Among primary immunodefiencies, chronic granulomatous disease (CGD) has the highest prevalence of invasive fungal diseases. Voriconazole is recommended for the primary treatment of invasive aspergillosis in most patients. In patients whose aspergillosis is refractory to voriconazole, therapeutic options include changing class of antifungal, for example using an amphotericin B formulation, an...

  13. Prediction of Antifungal Activity of Gemini Imidazolium Compounds

    Directory of Open Access Journals (Sweden)

    Łukasz Pałkowski

    2015-01-01

    Full Text Available The progress of antimicrobial therapy contributes to the development of strains of fungi resistant to antimicrobial drugs. Since cationic surfactants have been described as good antifungals, we present a SAR study of a novel homologous series of 140 bis-quaternary imidazolium chlorides and analyze them with respect to their biological activity against Candida albicans as one of the major opportunistic pathogens causing a wide spectrum of diseases in human beings. We characterize a set of features of these compounds, concerning their structure, molecular descriptors, and surface active properties. SAR study was conducted with the help of the Dominance-Based Rough Set Approach (DRSA, which involves identification of relevant features and relevant combinations of features being in strong relationship with a high antifungal activity of the compounds. The SAR study shows, moreover, that the antifungal activity is dependent on the type of substituents and their position at the chloride moiety, as well as on the surface active properties of the compounds. We also show that molecular descriptors MlogP, HOMO-LUMO gap, total structure connectivity index, and Wiener index may be useful in prediction of antifungal activity of new chemical compounds.

  14. Probiotics as Antifungals in Mucosal Candidiasis.

    Science.gov (United States)

    Matsubara, Victor H; Bandara, H M H N; Mayer, Marcia P A; Samaranayake, Lakshman P

    2016-05-01

    Candidais an opportunistic pathogen that causes mucosal and deep systemic candidiasis. The emergence of drug resistance and the side effects of currently available antifungals have restricted their use as long-term prophylactic agents for candidal infections. Given this scenario, probiotics have been suggested as a useful alternative for the management of candidiasis. We analyzed the available data on the efficacy of probiotics in candidal colonization of host surfaces. A number of well-controlled studies indicate that probiotics, particularly lactobacilli, suppressCandidagrowth and biofilm development in vitro.A few clinical trials have also shown the beneficial effects of probiotics in reducing oral, vaginal, and enteric colonization byCandida; alleviation of clinical signs and symptoms; and, in some cases, reducing the incidence of invasive fungal infection in critically ill patients. Probiotics may serve in the future as a worthy ally in the battle against chronic mucosal candidal infections. PMID:26826375

  15. Biochemical approaches to selective antifungal activity. Focus on azole antifungals.

    Science.gov (United States)

    Vanden Bossche, H; Marichal, P; Gorrens, J; Coene, M C; Willemsens, G; Bellens, D; Roels, I; Moereels, H; Janssen, P A

    1989-01-01

    Azole antifungals (e.g. the imidazoles: miconazole, clotrimazole, bifonazole, imazalil, ketoconazole, and the triazoles: diniconazole, triadimenol, propiconazole, fluconazole and itraconazole) inhibit in fungal cells the 14 alpha-demethylation of lanosterol or 24-methylenedihydrolanosterol. The consequent inhibition of ergosterol synthesis originates from binding of the unsubstituted nitrogen (N-3 or N-4) of their imidazole or triazole moiety to the heme iron and from binding of their N-1 substituent to the apoprotein of a cytochrome P-450 (P-450(14)DM) of the endoplasmic reticulum. Great differences in both potency and selectivity are found between the different azole antifungals. For example, after 16h of growth of Candida albicans in medium supplemented with [14C]-acetate and increasing concentrations of itraconazole, 100% inhibition of ergosterol synthesis is achieved at 3 x 10(-8) M. Complete inhibition of this synthesis by fluconazole is obtained at 10(-5) M only. The agrochemical imidazole derivative, imazalil, shows high selectivity, it has almost 80 and 98 times more affinity for the Candida P-450(s) than for those of the piglet testes microsomes and bovine adrenal mitochondria, respectively. However, the topically active imidazole antifungal, bifonazole, has the highest affinity for P-450(s) of the testicular microsomes. The triazole antifungal itraconazole inhibits at 10(-5) M the P-450-dependent aromatase by 17.9, whereas 50% inhibition of this enzyme is obtained at about 7.5 x 10(-6)M of the bistriazole derivative fluconazole. The overall results show that both the affinity for the fungal P-450(14)DM and the selectivity are determined by the nitrogen heterocycle and the hydrophobic N-1 substituent of the azole antifungals. The latter has certainly a greater impact. The presence of a triazole and a long hypdrophobic nonligating portion form the basis for itraconazole's potency and selectivity.

  16. Antifungal activity of multifunctional Fe{sub 3}O{sub 4}-Ag nanocolloids

    Energy Technology Data Exchange (ETDEWEB)

    Chudasama, Bhupendra, E-mail: bnchudasama@thapar.ed [School of Physics and Materials Science, Thapar University, Patiala 147004 (India); Vala, Anjana K.; Andhariya, Nidhi [Department of Physics, Bhavnagar University, Bhavnagar 364022 (India); Upadhyay, R.V. [P.D. Patel Institute of Applied Sciences, Charotar University of Science and Technology, Changa 388421 (India); Mehta, R.V. [Department of Physics, Bhavnagar University, Bhavnagar 364022 (India)

    2011-05-15

    In recent years, rapid increase has been observed in the population of microbes that are resistant to conventionally used antibiotics. Antifungal drug therapy is no exception and now resistance to many of the antifungal agents in use has emerged. Therefore, there is an inevitable and urgent medical need for antibiotics with novel antimicrobial mechanisms. Aspergillus glaucus is the potential cause of fatal brain infections and hypersensitivity pneumonitis in immunocompromised patients and leads to death despite aggressive multidrug antifungal therapy. In the present article, we describe the antifungal activity of multifunctional core-shell Fe{sub 3}O{sub 4}-Ag nanocolloids against A. glaucus isolates. Controlled experiments are also carried out with Ag nanocolloids in order to understand the role of core (Fe{sub 3}O{sub 4}) in the antifungal action. The minimum inhibitory concentration (MIC) of nanocolloids is determined by the micro-dilution method. MIC of A. glaucus is 2000 {mu}g/mL. The result is quite promising and requires further investigations in order to develop a treatment methodology against this death causing fungus in immunocompromised patients. - Research Highlights: Synthesis of Fe{sub 3}O{sub 4}-Ag core-shell nanocolloids. Antifungal activity of Fe{sub 3}O{sub 4}-Ag nanocolloids against Aspergillus glaucus isolates. The MIC value for A. glaucus is 2000 {mu}g/mL. Antifungal activity is better or comparable with most prominent antibiotics.

  17. Synthesis, Characterization and Antifungal Evaluation of Novel Thiochromanone Derivatives Containing Indole Skeleton.

    Science.gov (United States)

    Han, Xiao-Yan; Zhong, Yi-Fan; Li, Sheng-Bin; Liang, Guo-Chao; Zhou, Guan; Wang, Xiao-Ke; Chen, Bao-Hua; Song, Ya-Li

    2016-09-01

    Invasive fungal disease constitutes a growing health problem and development of novel antifungal drugs with high potency and selectivity against new fungal molecular targets are urgently needed. In order to develop potent antifungal agents, a novel series of 6-alkyl-indolo[3,2-c]-2H-thiochroman derivatives were synthesized. Microdilution broth method was used to investigate antifungal activity of these compounds. Most of them showed good antifungal activity in vitro. Compound 4o showed the best antifungal activity, which (inhibition of Candida albicans and Cryptococcus neoformans) can be achieved at the concentration of 4 µg/mL. Compounds 4b (inhibition of Cryptococcus neoformans), 4j (inhibition of Cryptococcus neoformans), 4d (inhibition of Candida albicans) and 4h (inhibition of Candida albicans) also showed the best antifungal activity at the concentrations of 4 µg/mL. The molecular interactions between 4o and the N-myristoyltransferase of Candida albicans (PDB ID: 1IYL) were finally investigated through molecular docking. The results indicated that these thiochromanone derivatives containing indole skeleton could serve as promising leads for further optimization as novel antifungal agents. PMID:27373770

  18. Antifungal activity of juniper extracts

    Science.gov (United States)

    Sawdust from three species of Juniperus (i.e., J. virginianna, J. occidentalis, and J. ashei) were extracted with hexane or ethanol and the extracts tested for antifungal activity against four species of wood-rot fungi. These species studied represent the junipers with the greatest potential for co...

  19. 我院2009-2011年老年真菌感染菌种分布及其对抗真菌药敏感性分析%Analysis of Species Distribution and Drug Susceptibility to Antifungal Agents in the Aged with Fungal Infection of Our Hospital during 2009-2011

    Institute of Scientific and Technical Information of China (English)

    张慧儿; 裘莉佩

    2013-01-01

    目的:探讨临床老年患者标本中所分离的假丝酵母菌属的菌种分布及其对临床常用抗真菌药的敏感性,为老年人使用抗真菌药提供参考.方法:对我院2009-2011年从老年体内分离的213例假丝酵母菌进行回顾性分析,分析其菌种分布情况以及对5种抗真菌药的敏感性.结果:在213株假丝酵母菌中,白假丝酵母菌占42.3%(90/213),非白假丝酵母菌占57.7% (123/213);5-氟胞嘧啶、两性霉素B、氟康唑、伊曲康唑和伏立康唑的总敏感率分别为87.8%、100%、93.2%、85.9%和95.9%;90株白假丝酵母菌对上述5种抗真菌药的敏感率分别为93.3%、100%、95.4%、92.2%和96.3%,123株非白假丝酵母菌分别为83.7%、100%、91.6%、81.3%和95.6%.结论:在老年感染假丝酵母菌中最常见的菌种仍是白假丝酵母菌,但其比例较已报道的非老年感染者比例有所下降;白假丝酵母菌对常用抗真菌药仍有较高的敏感性,非白假丝酵母菌的耐药性则高于白假丝酵母菌.%OBJECTIVE: To discuss the species distribution and drug susceptibility to antifungal agent of isolated Candida, and to provide reference for the use of antifungal agent in the aged. METHODS: A total of 213 isolates were collected from our hospital during 2009 — 2011 were analyzed statistically, and the species distribution of Candida and drug resistance to 5 commonly used antifungal agents were analyzed. RESULTS: Among 213 Candida, Candida albicans accounted for 42.3% (90/213) and non-Candida albicans accounted for 57.7% (123/213). The overall percentage of strains susceptible to 5-flucytosine, amphotericin B, flucytosine, itraconazole and voriconazole were 87.8% , 100% , 93.2% , 85.9% and 95.9% , respectively. About 93.3% , 100%, 95.4% , 92.2% and 96.3% of 90 strains of Candida albicans were susceptible to these 5 antifungal agents. The susceptibility rates of 123 non-Candida albicans isolates were 83.7%, 100

  20. Self-assembled cardanol azo derivatives as antifungal agent with chitin-binding ability.

    Science.gov (United States)

    Mahata, Denial; Mandal, Santi M; Bharti, Rashmi; Gupta, Vinay Krishna; Mandal, Mahitosh; Nag, Ahindra; Nando, Golok B

    2014-08-01

    Cardanol is a non-isoprenoic phenolic lipid-mixture of distilled cashew nut shell liquid obtained from Anacardium occidentale. Herein, cardanol is purified from cashew nut shell liquid (CNSL) and synthesized to new compounds with different azo amphiphiles. These synthesized compounds are allowed to self-assembled in hydrophobic environment and checked antifungal activity against Candida albicans. Self-assembled structure of CABA showed higher antifungal activity (16μg/mL) and chitin-binding ability in comparison to CAP and CANB. Furthermore, the self-assembled azo amphiphiles are immobilized with silver ions to prepare hydrogel which showed eight folds enhanced antifungal activity. Toxicity is reduced by several folds of self-assembled or hydrogel structure in comparison to pure compounds. Thus, the self-assembled structure of amphiphiles and their hydrogels have been found to be new macromolecules of interest with potential use as antifungal drugs. PMID:24836571

  1. Novel hybrids of fluconazole and furanones: design, synthesis and antifungal activity.

    Science.gov (United States)

    Borate, Hanumant B; Sawargave, Sangmeshwer P; Chavan, Subhash P; Chandavarkar, Mohan A; Iyer, Ramki; Tawte, Amit; Rao, Deepali; Deore, Jaydeep V; Kudale, Ananada S; Mahajan, Pankaj S; Kangire, Gopinath S

    2011-08-15

    During our efforts to develop new antifungal agents, a number of hybrid molecules containing furanones and fluconazole pharmacophores were designed and synthesized. The new chemical entities thus synthesized were tested for their potential as antifungal agents against various fungal strains and it was observed that the compounds with general structure 7 were potent inhibitors of Candida albicans ATCC 24433, Candida glabrata ATCC 90030, Candida tropicalis ATCC 750 and Candida neoformans ATCC 34664 while the fluconazole analogues 12 exhibited antifungal activity against Candida albicans ATCC 24433 and Candida glabrata ATCC 90030. The structure-activity relationship for these compounds is discussed. The synthetic strategies used in the present work have potential to prepare a large number of compounds for further refinement of structures to obtain molecules suitable for development as antifungal drugs. PMID:21757344

  2. Two small molecule lead compounds as new antifungal agents effective against Candida albicans and Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Yones Pilehvar-Soltanahmadi

    2014-06-01

    Full Text Available  Background: Antifungal drug resistance and few numbers of available drugs limit therapeutic options against fungal infections. The present study was designed to discover new antifungal drugs. Materials and Methods: This study was carried out in two separate steps, that is, in silico lead identification and in vitro assaying of antifungal potential. A structural data file of a ternary complex of fusicuccin (legend, C terminus of H+-ATPase and 14-3-3 regulatory protein (1o9F.pdb file was used as a model. Computational screening of a virtual 3D database of drug-like molecules was performed and selected small molecules, resembling the functional part of the ligand performing ligand docking, were tested using ArgusLab (4.0.1. Two lead compounds, 3-Cyclohexan propionic acid (CXP and 4-phenyl butyric acid (PBA were selected according to their ligation scores. Standard Strains of Candida albicans and Saccharomyces cerevisiae were used to measure the antifungal potential of the two identified lead compounds against the fungi using micro-well plate dilution assay. Results: Ligation scores for CXP and PBA were -9.33744 and -10.7259 kcal/mol, respectively, and MIC and MFC of CXP and PBA against the two yeasts were promising. Conclusion: The evidence from the present study suggests that CXP and PBA possess potentially antifungals properties. 

  3. Characterization of Tamoxifen as an Antifungal Agent Using the Yeast Schizosaccharomyces Pombe Model Organism.

    Science.gov (United States)

    Zhang, Xibo; Fang, Yue; Jaiseng, Wurentuya; Hu, Lingling; Lu, Yabin; Ma, Yan; Furuyashiki, Tomoyuki

    2015-01-01

    Tamoxifen, a selective estrogen receptor modulator used for managing breast cancer, is known to have antifungal activity. However, its molecular mechanism remains unknown. Using the fission yeast Schizosaccharomyces pombe as a model organism, we have explored the mechanism involved in antifungal action of tamoxifen. Since tamoxifen was shown to inhibit the binding of calmodulin to calcineurin in fungi, we first examined involvement of these molecules and found that overexpression of a catalytic subunit of calcineurin and its constitutively active mutant as well as calmodulin increases tamoxifen sensitivity. Since terbinafine and azoles inhibit enzymes for ergosterol biosynthesis, Erg1 and Erg11, for their antifungal actions, we also examined involvement of these molecules. Overexpression of Erg1 and Erg11 reduced the sensitivity to terbinafine and azoles, respectively, but increased tamoxifen sensitivity, suggesting that ergosterol biosynthesis is differently related to the action of tamoxifen and those of terbinafine and azoles. To elucidate molecules involved in tamoxifen action, we performed a genome-wide screen for altered sensitivity to tamoxifen using a fission yeast gene deletion library, and identified various hypersensitive and resistant mutants to this drug. Notably, these mutants are rarely overlapped with those identified in similar genetic screens with currently used antifungals, suggesting a novel mode of antifungal action. Furthermore, tamoxifen augmented antifungal actions of terbinafine and azoles, suggesting synergetic actions between these drugs. Therefore, our findings suggest that calmodulin-calcineurin pathway and ergosterol biosynthesis are related to antifungal action of tamoxifen, and propose novel targets for antifungal development as well as combined therapy with tamoxifen for fungal diseases. PMID:26628015

  4. Antifungal activity of topical microemulsion containing a thiophene derivative

    Directory of Open Access Journals (Sweden)

    Geovani Pereira Guimarães

    2014-06-01

    Full Text Available Fungal infections have become a major problem of worldwide concern. Yeasts belonging to the Candida genus and the pathogenic fungus Cryptococcus neoformans are responsible for different clinical manifestations, especially in immunocompromised patients. Antifungal therapies are currently based on a few chemotherapeutic agents that have problems related to effectiveness and resistance profiles. Microemulsions are isotropic, thermodynamically stable transparent systems of oil, water and surfactant that can improve the solubilization of lipophilic drugs. Taking into account the need for more effective and less toxic drugs along with the potential of thiophene derivatives as inhibitors of pathogenic fungi growth, this study aimed to evaluate the antifungal activity of a thiophene derivative (5CN05 embedded in a microemulsion (ME. The minimum inhibitory concentration (MIC was determined using the microdilution method using amphotericin B as a control. The formulations tested (ME- blank and ME-5CN05 showed physico-chemical properties that would allow their use by the topical route. 5CN05 as such exhibited moderate or weak antifungal activity against Candida species (MIC = 270-540 µg.mL-1 and good activity against C. neoformans (MIC = 17 µg.mL-1. Candida species were susceptible to ME-5CN05 (70-140 µg.mL-1, but C. neoformans was much more, presenting a MIC value of 2.2 µg.mL-1. The results of this work proved promising for the pharmaceutical industry, because they suggest an alternative therapy against C. neoformans.

  5. A Comparative Study of the Anti-Fungal Activity of Zinc Oxide and Titanium Dioxide Nano and Bulk Particles with Anti-Fungals against Fungi Isolated from Infected Skin and Dandruff Flakes

    Directory of Open Access Journals (Sweden)

    Sara A George

    2014-06-01

    Full Text Available The anti-fungal activity of Zinc oxide and Titanium dioxide nano-particles was assessed by treating eight fungal cultures - Aspergillus niger, Trichophyton, Fonsecaea, Aspergillus flavus, Rhizopus oryzae, Fusarium, Ramichloridium schulzeri and Cladosporium, isolated from infected skin and dandruff flakes with the nanoparticles and analysing the extent of growth inhibition on agar and in broth media. The anti-fungal activity of these nano-particles was also compared to that of their respective bulk-particular forms, as well as to two commonly used anti-fungals, namely Amphotericin-B and Miconazole. The nano-particles were found to be more effective than the bulk-particles and almost equally efficient as Amphotericin-B, however Miconazole was found to be a better anti-fungal at an equal concentration. Zinc oxide nano-particles were better anti-fungals than Titanium dioxide, thus its anti-fungal activity at different concentrations was assessed to identify the concentration that shows similar anti-fungal activity as 3μg/ml of Miconazole. The reason for performing this study was to investigate the possibility of replacing presently used anti-fungal drugs with nano-particles in topical applications to treat mycosis.

  6. Conventional and alternative antifungal therapies to oral candidiasis

    Directory of Open Access Journals (Sweden)

    Paula Cristina Anibal

    2010-12-01

    Full Text Available Candida-associated denture stomatitis is the most common form of oral candidal infection, with Candida albicans being the principal etiological agent. Candida adheres directly or via an intermediary layer of plaque-forming bacteria to denture acrylic. Despite antifungal therapy to treat denture stomatitis, infection is reestablished soon after the treatment ceases. In addition, many predisposing factors have been identified as important in the development of oral candidiasis, including malnourishment, common endocrine disorders, such as diabetis mellitus, antibacterial drug therapy, corticosteroids, radiotherapy and other immunocompromised conditions, such as acquired immunodeficiency syndrome (AIDS. These often results in increased tolerance to the most commonly used antifungals. So this review suggests new therapies to oral candidiasis.

  7. Conventional and alternative antifungal therapies to oral candidiasis.

    Science.gov (United States)

    Anibal, Paula Cristina; de Cássia Orlandi Sardi, Janaina; Peixoto, Iza Teixeira Alves; de Carvalho Moraes, Julianna Joanna; Höfling, José Francisco

    2010-10-01

    Candida-associated denture stomatitis is the most common form of oral candidal infection, with Candida albicans being the principal etiological agent. Candida adheres directly or via an intermediary layer of plaque-forming bacteria to denture acrylic. Despite antifungal therapy to treat denture stomatitis, infection is reestablished soon after the treatment ceases. In addition, many predisposing factors have been identified as important in the development of oral candidiasis, including malnourishment, common endocrine disorders, such as diabetis mellitus, antibacterial drug therapy, corticosteroids, radiotherapy and other immunocompromised conditions, such as acquired immunodeficiency syndrome (AIDS). These often results in increased tolerance to the most commonly used antifungals. So this review suggests new therapies to oral candidiasis.

  8. Evaluation of vaginal antifungal formulations in vivo.

    Science.gov (United States)

    McRipley, R. J.; Erhard, P. J.; Schwind, R. A.; Whitney, R. R.

    1979-01-01

    Relatively simple and rapid procedures have been developed for evaluating the local efficacy of vaginal antifungal agents in vivo in a vaginal candidiasis model in ovariectomized rats. The results of this investigation indicate that the model and methods described are quite suitable for screening potential antifungal substances and for assessing the chemotherapeutic effectiveness of new antifungal agents and formulations before carrying out clinical studies. PMID:392480

  9. Antifungal Activity of C-27 Steroidal Saponins

    OpenAIRE

    Yang, Chong-Ren; Zhang, Ying; Jacob, Melissa R.; Khan, Shabana I.; Zhang, Ying-Jun; Li, Xing-Cong

    2006-01-01

    As part of our search for new antifungal agents from natural resources, 22 C-27 steroidal saponins and 6 steroidal sapogenins isolated from several monocotyledonous plants were tested for their antifungal activity against the opportunistic pathogens Candida albicans, Candida glabrata, Candida krusei, Cryptococcus neoformans, and Aspergillus fumigatus. The results showed that the antifungal activity of the steroidal saponins was associated with their aglycone moieties and the number and struct...

  10. Antifungal Activity of Micafungin in Serum ▿

    OpenAIRE

    Ishikawa, Jun; Maeda, Tetsuo; Matsumura, Itaru; Yasumi, Masato; Ujiie, Hidetoshi; Masaie, Hiroaki; Nakazawa, Tsuyoshi; Mochizuki, Nobuo; Kishino, Satoshi; Kanakura, Yuzuru

    2009-01-01

    We have evaluated the antifungal activity of micafungin in serum by using the disk diffusion method with serum-free and serum-added micafungin standard curves. Serum samples from micafungin-treated patients have been shown to exhibit adequate antifungal activity, which was in proportion to both the applied dose and the actual concentration of micafungin measured by high-performance liquid chromatography. The antifungal activity of micafungin in serum was also confirmed with the broth microdil...

  11. Antibacterial and Antifungal Compounds from Marine Fungi

    OpenAIRE

    Lijian Xu; Wei Meng; Cong Cao; Jian Wang; Wenjun Shan; Qinggui Wang

    2015-01-01

    This paper reviews 116 new compounds with antifungal or antibacterial activities as well as 169 other known antimicrobial compounds, with a specific focus on January 2010 through March 2015. Furthermore, the phylogeny of the fungi producing these antibacterial or antifungal compounds was analyzed. The new methods used to isolate marine fungi that possess antibacterial or antifungal activities as well as the relationship between structure and activity are shown in this review.

  12. In Vitro Antifungal Activity of Kampo Medicine Water Extracts against Trichophyton rubrum.

    Science.gov (United States)

    Da, Xia; Takahashi, Hitoshi; Hein, Kyaw Zaw; Morita, Eishin

    2016-06-01

    Kampo medicines consist of a variety of crude animal, plant, and mineral extracts that have long been used to relieve different symptoms, and are relatively safe. However, their mechanisms of actions have not been well investigated. We screened 61 commercially available Kampo medicines to determine if they contain constituents with antifungal activity against Trichophyton rubrum. The antifungal effect of the Kampo medicines was determined by measuring the mean absorbance of treated fungal culture media. Lower absorbance values suggested a higher inhibition of the growth rate of T. rubrum by the Kampo medicines. We found that seven of the evaluated formulations exhibited a comparable antifungal activity to that of fluconazole at 14 mg/mL. The seven active Kampo medicines were Saiko-keishi-kankyou-to, Saiko-ka-ryukotsu-borei-to, Saiko-keishi-to, Keishi-ka-ryukotsu-borei-to, Dai-saiko-to, Bohu-tsu-sho-san, and Otsu-ji-to. The seven Kampo medicines with antifungal activity contain 30 different crude extracts, and Ou-gon (Scutellaria root) is a supplement contained in six of the seven formulations. Therefore, Ou-gon was considered to play a major role in their antifungal effect. The antifungal assay of the Ou-gon water extract showed that it significantly inhibited the growth of T. rubrum at a concentration of 20 mg/mL. Future studies will focus on the isolation and identification of the antifungal components of the crude extracts of Ou-gon, which may be potentially useful, new, and safe antifungal drugs. PMID:27534111

  13. Correlation between Plant Secondary Metabolites and Their Antifungal Mechanisms–A Review

    DEFF Research Database (Denmark)

    Freiesleben, Sara; Jäger, Anna

    2014-01-01

    The search for new antifungal drugs often involves secondary metabolites from plants because of their pharmacological activity against foreign pathogens. Among the modern drugs in use today about 40% are of natural origin. To distinguish the secondary metabolites they can be divided into groups...... search for existing knowledge about antifungal mechanisms of different secondary metabolites from plants. The secondary metabolites have been grouped into three major groups according to their biosynthetic origin, and into subgroups according to their structure. There seems to be a correlation between...... biosynthetic groups of secondary metabolites; the phenolic compounds and the nitrogen containing compounds. Despite this there are correlations between some of the subgroups and their antifungal mechanism of actions....

  14. Candida Infections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents

    Directory of Open Access Journals (Sweden)

    Claudia Spampinato

    2013-01-01

    Full Text Available The genus Candida includes about 200 different species, but only a few species are human opportunistic pathogens and cause infections when the host becomes debilitated or immunocompromised. Candida infections can be superficial or invasive. Superficial infections often affect the skin or mucous membranes and can be treated successfully with topical antifungal drugs. However, invasive fungal infections are often life-threatening, probably due to inefficient diagnostic methods and inappropriate initial antifungal therapies. Here, we briefly review our current knowledge of pathogenic species of the genus Candida and yeast infection causes and then focus on current antifungal drugs and resistance mechanisms. An overview of new therapeutic alternatives for the treatment of Candida infections is also provided.

  15. Melanins Protect Sporothrix brasiliensis and Sporothrix schenckii from the Antifungal Effects of Terbinafine.

    Science.gov (United States)

    Almeida-Paes, Rodrigo; Figueiredo-Carvalho, Maria Helena Galdino; Brito-Santos, Fábio; Almeida-Silva, Fernando; Oliveira, Manoel Marques Evangelista; Zancopé-Oliveira, Rosely Maria

    2016-01-01

    Terbinafine is a recommended therapeutic alternative for patients with sporotrichosis who cannot use itraconazole due to drug interactions or side effects. Melanins are involved in resistance to antifungal drugs and Sporothrix species produce three different types of melanin. Therefore, in this study we evaluated whether Sporothrix melanins impact the efficacy of antifungal drugs. Minimal inhibitory concentrations (MIC) and minimal fungicidal concentrations (MFC) of two Sporothrix brasiliensis and four Sporothrix schenckii strains grown in the presence of the melanin precursors L-DOPA and L-tyrosine were similar to the MIC determined by the CLSI standard protocol for S. schenckii susceptibility to amphotericin B, ketoconazole, itraconazole or terbinafine. When MICs were determined in the presence of inhibitors to three pathways of melanin synthesis, we observed, in four strains, an increase in terbinafine susceptibility in the presence of tricyclazole, a DHN-melanin inhibitor. In addition, one S. schenckii strain grown in the presence of L-DOPA had a higher MFC value when compared to the control. Growth curves in presence of 2×MIC concentrations of terbinafine showed that pyomelanin and, to a lesser extent, eumelanin were able to protect the fungi against the fungicidal effect of this antifungal drug. Our results suggest that melanin protects the major pathogenic species of the Sporothrix complex from the effects of terbinafine and that the development of new antifungal drugs targeting melanin synthesis may improve sporotrichosis therapies.

  16. Melanins Protect Sporothrix brasiliensis and Sporothrix schenckii from the Antifungal Effects of Terbinafine.

    Directory of Open Access Journals (Sweden)

    Rodrigo Almeida-Paes

    Full Text Available Terbinafine is a recommended therapeutic alternative for patients with sporotrichosis who cannot use itraconazole due to drug interactions or side effects. Melanins are involved in resistance to antifungal drugs and Sporothrix species produce three different types of melanin. Therefore, in this study we evaluated whether Sporothrix melanins impact the efficacy of antifungal drugs. Minimal inhibitory concentrations (MIC and minimal fungicidal concentrations (MFC of two Sporothrix brasiliensis and four Sporothrix schenckii strains grown in the presence of the melanin precursors L-DOPA and L-tyrosine were similar to the MIC determined by the CLSI standard protocol for S. schenckii susceptibility to amphotericin B, ketoconazole, itraconazole or terbinafine. When MICs were determined in the presence of inhibitors to three pathways of melanin synthesis, we observed, in four strains, an increase in terbinafine susceptibility in the presence of tricyclazole, a DHN-melanin inhibitor. In addition, one S. schenckii strain grown in the presence of L-DOPA had a higher MFC value when compared to the control. Growth curves in presence of 2×MIC concentrations of terbinafine showed that pyomelanin and, to a lesser extent, eumelanin were able to protect the fungi against the fungicidal effect of this antifungal drug. Our results suggest that melanin protects the major pathogenic species of the Sporothrix complex from the effects of terbinafine and that the development of new antifungal drugs targeting melanin synthesis may improve sporotrichosis therapies.

  17. Melanins Protect Sporothrix brasiliensis and Sporothrix schenckii from the Antifungal Effects of Terbinafine.

    Science.gov (United States)

    Almeida-Paes, Rodrigo; Figueiredo-Carvalho, Maria Helena Galdino; Brito-Santos, Fábio; Almeida-Silva, Fernando; Oliveira, Manoel Marques Evangelista; Zancopé-Oliveira, Rosely Maria

    2016-01-01

    Terbinafine is a recommended therapeutic alternative for patients with sporotrichosis who cannot use itraconazole due to drug interactions or side effects. Melanins are involved in resistance to antifungal drugs and Sporothrix species produce three different types of melanin. Therefore, in this study we evaluated whether Sporothrix melanins impact the efficacy of antifungal drugs. Minimal inhibitory concentrations (MIC) and minimal fungicidal concentrations (MFC) of two Sporothrix brasiliensis and four Sporothrix schenckii strains grown in the presence of the melanin precursors L-DOPA and L-tyrosine were similar to the MIC determined by the CLSI standard protocol for S. schenckii susceptibility to amphotericin B, ketoconazole, itraconazole or terbinafine. When MICs were determined in the presence of inhibitors to three pathways of melanin synthesis, we observed, in four strains, an increase in terbinafine susceptibility in the presence of tricyclazole, a DHN-melanin inhibitor. In addition, one S. schenckii strain grown in the presence of L-DOPA had a higher MFC value when compared to the control. Growth curves in presence of 2×MIC concentrations of terbinafine showed that pyomelanin and, to a lesser extent, eumelanin were able to protect the fungi against the fungicidal effect of this antifungal drug. Our results suggest that melanin protects the major pathogenic species of the Sporothrix complex from the effects of terbinafine and that the development of new antifungal drugs targeting melanin synthesis may improve sporotrichosis therapies. PMID:27031728

  18. Melanins Protect Sporothrix brasiliensis and Sporothrix schenckii from the Antifungal Effects of Terbinafine

    Science.gov (United States)

    Almeida-Paes, Rodrigo; Figueiredo-Carvalho, Maria Helena Galdino; Brito-Santos, Fábio; Almeida-Silva, Fernando; Oliveira, Manoel Marques Evangelista; Zancopé-Oliveira, Rosely Maria

    2016-01-01

    Terbinafine is a recommended therapeutic alternative for patients with sporotrichosis who cannot use itraconazole due to drug interactions or side effects. Melanins are involved in resistance to antifungal drugs and Sporothrix species produce three different types of melanin. Therefore, in this study we evaluated whether Sporothrix melanins impact the efficacy of antifungal drugs. Minimal inhibitory concentrations (MIC) and minimal fungicidal concentrations (MFC) of two Sporothrix brasiliensis and four Sporothrix schenckii strains grown in the presence of the melanin precursors L-DOPA and L-tyrosine were similar to the MIC determined by the CLSI standard protocol for S. schenckii susceptibility to amphotericin B, ketoconazole, itraconazole or terbinafine. When MICs were determined in the presence of inhibitors to three pathways of melanin synthesis, we observed, in four strains, an increase in terbinafine susceptibility in the presence of tricyclazole, a DHN-melanin inhibitor. In addition, one S. schenckii strain grown in the presence of L-DOPA had a higher MFC value when compared to the control. Growth curves in presence of 2×MIC concentrations of terbinafine showed that pyomelanin and, to a lesser extent, eumelanin were able to protect the fungi against the fungicidal effect of this antifungal drug. Our results suggest that melanin protects the major pathogenic species of the Sporothrix complex from the effects of terbinafine and that the development of new antifungal drugs targeting melanin synthesis may improve sporotrichosis therapies. PMID:27031728

  19. Antifungal susceptibility testing method for resource constrained laboratories

    Directory of Open Access Journals (Sweden)

    Khan S

    2006-01-01

    Full Text Available Purpose: In resource-constrained laboratories of developing countries determination of antifungal susceptibility testing by NCCLS/CLSI method is not always feasible. We describe herein a simple yet comparable method for antifungal susceptibility testing. Methods: Reference MICs of 72 fungal isolates including two quality control strains were determined by NCCLS/CLSI methods against fluconazole, itraconazole, voriconazole, amphotericin B and cancidas. Dermatophytes were also tested against terbinafine. Subsequently, on selection of optimum conditions, MIC was determined for all the fungal isolates by semisolid antifungal agar susceptibility method in Brain heart infusion broth supplemented with 0.5% agar (BHIA without oil overlay and results were compared with those obtained by reference NCCLS/CLSI methods. Results: Comparable results were obtained by NCCLS/CLSI and semisolid agar susceptibility (SAAS methods against quality control strains. MICs for 72 isolates did not differ by more than one dilution for all drugs by SAAS. Conclusions: SAAS using BHIA without oil overlay provides a simple and reproducible method for obtaining MICs against yeast, filamentous fungi and dermatophytes in resource-constrained laboratories.

  20. Tolerance of yeast biofilm cells towards systemic antifungals

    DEFF Research Database (Denmark)

    Bojsen, Rasmus Kenneth

    Fungal infections have become a major problem in the hospital sector in the past decades due to the increased number of immune compromised patients susceptible to mycosis. Most human infections are believed to be associated with biofilm forming cells that are up to 1000-fold more tolerant to anti...... that complex sphingolipids were involved in fungicidal activity of LTX-109. The sphingolipids may therefore represent a unique antifungal target with therapeutic potential for future drug development....... to antimicrobial agents compared to their planktonic counterparts. Antifungal treatment of biofilms will therefore often result in treatment failure. Consequently, there is a basic requirement to understand the underlying tolerance mechanisms and to development of novel anti-biofilm treatment strategies. The focus...... of this thesis has been to explore the tolerance mechanisms of yeast biofilms to systemic antifungal agents and to identify the molecular target of a novel peptidomimetic with anti-biofilm activity. The genetic tractable S. cerevisiae was used as biofilm model system for the pathogenic Candida species...

  1. Epidemiology and antifungal susceptibilities of yeasts causing vulvovaginitis in a teaching hospital.

    Science.gov (United States)

    Gamarra, Soledad; Morano, Susana; Dudiuk, Catiana; Mancilla, Estefanía; Nardin, María Elena; de Los Angeles Méndez, Emilce; Garcia-Effron, Guillermo

    2014-10-01

    Vulvovaginal candidiasis is one of the most common mycosis. However, the information about antifungal susceptibilities of the yeasts causing this infection is scant. We studied 121 yeasts isolated from 118 patients with vulvovaginal candidiasis. The isolates were identified by phenotypic and molecular methods, including four phenotypic methods described to differentiate Candida albicans from C. dubliniensis. Antifungal susceptibility testing was performed according to CLSI documents M27A3 and M27S4 using the drugs available as treatment option in the hospital. Diabetes, any antibacterial and amoxicillin treatment were statistically linked with vulvovaginal candidiasis, while oral contraceptives were not considered a risk factor. Previous azole-based over-the-counter antifungal treatment was statistically associated with non-C.albicans yeasts infections. The most common isolated yeast species was C. albicans (85.2 %) followed by C. glabrata (5 %), Saccharomyces cerevisiae (3.3 %), and C. dubliniensis (2.5 %). Fluconazole- and itraconazole-reduced susceptibility was observed in ten and in only one C. albicans strains, respectively. All the C. glabrata isolates showed low fluconazole MICs. Clotrimazole showed excellent potency against all but seven isolates (three C. glabrata, two S. cerevisiae, one C. albicans and one Picchia anomala). Any of the strains showed nystatin reduced susceptibility. On the other hand, terbinafine was the less potent drug. Antifungal resistance is still a rare phenomenon supporting the use of azole antifungals as empirical treatment of vulvovaginal candidiasis. PMID:25005365

  2. Antifungal saponins from Swartzia langsdorffii

    International Nuclear Information System (INIS)

    Chromatographic fractionation of the EtOH extract from the leaves of Swartzia langsdorffii afforded the pentacyclic triterpenes oleanolic acid and lupeol, and two saponins: oleanolic acid 3-sophoroside and the new ester 3-O-β-D-(6'-methyl)-glucopyranosyl-28-O-β-D-glucopyranosyl-oleanate.Their structures were elucidated from spectral data, including 2D NMR and HRESIMS experiments. Antifungal activity of all isolated compounds was evaluated, using phytopathogens Cladosporium cladosporioides and C. sphaerospermum, and human pathogens Candida albicans, C. krusei, C. parapsilosis and Cryptococcus neoformans. (author)

  3. Antifungal constituents of Melicope borbonica

    DEFF Research Database (Denmark)

    Simonsen, Henrik Toft; Adsersen, Anne; Bremner, Paul;

    2004-01-01

    Fractionation of extracts of the leaves of Melicope borbonica (syn. Euodia borbonica var. borbonica), a medicinal plant from the Réunion Island that is traditionally used for wound healing and other ailments, afforded an acetophenone (xanthoxylin) and two coumarins, scoparone and limettin......, as the major constituents. All three compounds exhibited moderate antifungal activity against Candida albicans and Penicillium expansum, in accordance with the traditional use of the plant. Moreover, 2,4,6-trimethoxyacetophenone (methylxanthoxylin), three other coumarins [7-(3-methyl-2-butenyloxy)-6...

  4. Diversity and antifungal susceptibility of Norwegian Candida glabrata clinical isolates

    Science.gov (United States)

    Andersen, Kari-Mette; Kristoffersen, Anne Karin; Ingebretsen, André; Vikholt, Katharina Johnsen; Örtengren, Ulf Thore; Olsen, Ingar; Enersen, Morten; Gaustad, Peter

    2016-01-01

    Background Increasing numbers of immunocompromised patients have resulted in greater incidence of invasive fungal infections with high mortality. Candida albicans infections dominate, but during the last decade, Candida glabrata has become the second highest cause of candidemia in the United States and Northern Europe. Reliable and early diagnosis, together with appropriate choice of antifungal treatment, is needed to combat these challenging infections. Objectives To confirm the identity of 183 Candida glabrata isolates from different human body sites using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and VITEK®2, and to analyze isolate protein profiles and antifungal susceptibility. The minimum inhibitory concentration (MIC) of seven antifungal drugs was determined for the isolates to elucidate susceptibility. Design A total of 183 C. glabrata isolates obtained between 2002 and 2012 from Norwegian health-care units were analyzed. For species verification and differentiation, biochemical characterization (VITEK®2) and mass spectrometry (MALDI–TOF) were used. MIC determination for seven antifungal drugs was undertaken using E-tests®. Results Using VITEK®2, 92.9% of isolates were identified as C. glabrata, while all isolates (100%) were identified as C. glabrata using MALDI-TOF. Variation in protein spectra occurred for all identified C. glabrata isolates. The majority of isolates had low MICs to amphotericin B (≤1 mg/L for 99.5%) and anidulafungin (≤0.06 mg/L for 98.9%). For fluconazole, 18% of isolates had MICs >32 mg/L and 82% had MICs in the range ≥0.016 mg/L to ≤32 mg/L. Conclusions Protein profiles and antifungal susceptibility characteristics of the C. glabrata isolates were diverse. Clustering of protein profiles indicated that many azole resistant isolates were closely related. In most cases, isolates had highest susceptibility to amphotericin B and anidulafungin. The results confirmed previous observations of high

  5. Design, synthesis of novel antifungal triazole derivatives with high activities against Aspergillus fumigatus

    Institute of Scientific and Technical Information of China (English)

    Qiu Qin He; Chao Mei Liu; Ke Li; Yong Bing Cao

    2007-01-01

    Based on the active site of Aspergillusfumigatus lanosterol 14α-demethylase (AF-CYP51), novel triazole compounds were designed. Their chemical synthesis and the antifungal activities were reported. The results showed that all the target compounds exhibited excellent activities with broad spectrum; in which compounds 4, 12 and 15 showed comparable activities against A.fumigatus to the control drug itraconazole.

  6. Design, synthesis and molecular docking studies of novel triazole antifungal compounds

    Institute of Scientific and Technical Information of China (English)

    Qiu Qin He; Ke Li; Yong Bing Cao; Huan Wen Dong; Li Hua Zhao; Chao Mei Liu; Chun Quan Sheng

    2007-01-01

    Based on the active site of Candida albicans lanosterol 14α-demethylase (CACYP51), novel triazole compounds structurally different from the current triazole drugs were designed and synthesized.In vitro antifungal activities showed that compounds 10,11,16 and 20 exhibited strong activities.In addition, compounds 10,11 and 16 also displayed certain activities against fluconazole-resistant fungi.

  7. Active packaging with antifungal activities.

    Science.gov (United States)

    Nguyen Van Long, N; Joly, Catherine; Dantigny, Philippe

    2016-03-01

    There have been many reviews concerned with antimicrobial food packaging, and with the use of antifungal compounds, but none provided an exhaustive picture of the applications of active packaging to control fungal spoilage. Very recently, many studies have been done in these fields, therefore it is timely to review this topic. This article examines the effects of essential oils, preservatives, natural products, chemical fungicides, nanoparticles coated to different films, and chitosan in vitro on the growth of moulds, but also in vivo on the mould free shelf-life of bread, cheese, and fresh fruits and vegetables. A short section is also dedicated to yeasts. All the applications are described from a microbiological point of view, and these were sorted depending on the name of the species. Methods and results obtained are discussed. Essential oils and preservatives were ranked by increased efficacy on mould growth. For all the tested molecules, Penicillium species were shown more sensitive than Aspergillus species. However, comparison between the results was difficult because it appeared that the efficiency of active packaging depended greatly on the environmental factors of food such as water activity, pH, temperature, NaCl concentration, the nature, the size, and the mode of application of the films, in addition to the fact that the amount of released antifungal compounds was not constant with time.

  8. Active packaging with antifungal activities.

    Science.gov (United States)

    Nguyen Van Long, N; Joly, Catherine; Dantigny, Philippe

    2016-03-01

    There have been many reviews concerned with antimicrobial food packaging, and with the use of antifungal compounds, but none provided an exhaustive picture of the applications of active packaging to control fungal spoilage. Very recently, many studies have been done in these fields, therefore it is timely to review this topic. This article examines the effects of essential oils, preservatives, natural products, chemical fungicides, nanoparticles coated to different films, and chitosan in vitro on the growth of moulds, but also in vivo on the mould free shelf-life of bread, cheese, and fresh fruits and vegetables. A short section is also dedicated to yeasts. All the applications are described from a microbiological point of view, and these were sorted depending on the name of the species. Methods and results obtained are discussed. Essential oils and preservatives were ranked by increased efficacy on mould growth. For all the tested molecules, Penicillium species were shown more sensitive than Aspergillus species. However, comparison between the results was difficult because it appeared that the efficiency of active packaging depended greatly on the environmental factors of food such as water activity, pH, temperature, NaCl concentration, the nature, the size, and the mode of application of the films, in addition to the fact that the amount of released antifungal compounds was not constant with time. PMID:26803804

  9. Antifungal agent utilization evaluation in hospitalized neutropenic cancer patients at a large teaching hospital

    Directory of Open Access Journals (Sweden)

    Vazin A

    2015-06-01

    Full Text Available Afsaneh Vazin,1 Mohammad Ali Davarpanah,2 Setareh Ghalesoltani3 1Department of Clinical Pharmacy, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran; 2HIV Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; 3International Branch of Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran Abstract: To evaluate pattern of using of three antifungal drugs: fluconazole, amphotericin B and voriconazole, at the hematology–oncology and bone marrow transplant wards of one large teaching hospital. In a prospective cross-sectional study, we evaluated the appropriateness of using antifungal drugs in patients, using Infectious Disease Society of America (IDSA and National Comprehensive Cancer Network (NCCN guidelines. All the data were recorded daily by a pharmacist in a form designed by a clinical pharmacist and infectious diseases specialist, for antifungals usage, administration, and monitoring. During the study, 116 patients were enrolled. Indications of prescribing amphotericin B, fluconazole, and voriconazole were appropriate according to guidelines in 83.4%, 80.6%, and 76.9% respectively. The duration of treatments were appropriate according to guidelines in 75%, 64.5%, and 71.1% respectively. The dose of voriconazole was appropriate according to guidelines in 46.2% of patients. None of the patients received salt loading before administration of amphotericin B. The most considerable problems with the mentioned antifungals were about the indications and duration of treatment. In addition, prehydration for amphotericin B and dosage of voriconazole were not completely compatible with the mentioned guidelines. A suitable combination of controlling the use of antifungals and educational programs could be essential for improving the general process of using antifungal drugs at our hospital. Keywords: utilization evaluation, fluconazole, amphotericin B, voriconazole, neutropenia

  10. Conazoles

    Directory of Open Access Journals (Sweden)

    Jan Heeres

    2010-06-01

    Full Text Available This review provides a historical overview of the analog based drug discovery of miconazole and its congeners, and is focused on marketed azole antifungals bearing the generic suffix “conazole”. The antifungal activity of miconazole, one of the first broad-spectrum antimycotic agents has been mainly restricted to topical applications. The attractive in vitro antifungal spectrum was a starting point to design more potent and especially orally active antifungal agents such as ketoconazole, itraconazole, posaconazole, fluconazole and voriconazole. The chemistry, in vitro and in vivo antifungal activity, pharmacology, and clinical applications of these marketed conazoles has been described.

  11. Essential pathway identification: from in silico analysis to potential antifungal targets in Aspergillus fumigatus

    DEFF Research Database (Denmark)

    Thykær, Jette; Andersen, Mikael Rørdam; Baker, S. E.

    2009-01-01

    Computational metabolic flux modeling has been a great aid for both understanding and manipulating microbial metabolism. A previously developed metabolic flux model for Aspergillus niger, an economically important biotechnology fungus known for protein and organic acid production, is comprised of...... essential reactions and pathways in Aspergillus spp. has promise to inform reverse genetic studies of gene essentiality and identify potential targets for antifungal development....... with the reactions, we identified orthologous candidate essential genes in Aspergillus fumigatus. Our predictions are validated in part by the modes of action for some antifungal drugs and by molecular genetic studies of essential genes in A. fumigatus and other fungi. The use of metabolic models to predict...

  12. Antifungal activity of essential oils of Origanum vulgare and Rosmarinus officinalis against three Candida albicans strains

    Directory of Open Access Journals (Sweden)

    Delić Dafina N.

    2013-01-01

    Full Text Available Due to general growing resistance and side effects to common antifungal drugs nowadays, there have been many studies reported on the use of herbal essential oils as antifungal agents in recent years. In this study, essential oils of Origanum vulgare and Rosmarinus officinalis (Lamiaceae were examined for their in vitro antifungal activity against three Candida albicans strains (laboratory - CAL, human pulmonary - CAH, and reference ATCC10231-CAR in comparison to Nystatin (0.30 mg/ml and Fluconazole (2 mg/ml as standard antifungal agents. The antifungal activity was evaluated by comparing inhibition zone diameters obtained both by disc-and well-diffusion assays, as well as by comparing MIC and MBC values detected by microdilution assay. Diffusion test results revealed stronger antifungal effect of O. vulgare against all analyzed C. albicans strains identifying CAL strain as the most susceptible one. Inhibition zones ranged from 12.65 to 25.10 mm depending on the concentrations applied. The highest concentrations of Rosemary essential oil (5.00 mg/ml demonstrated activity against two strains: CAL and CAR ATCC 10231 in both diffusion assays applied, while no antifungal activity was recorded against CAH isolate. Microdilution assay showed that both oils demonstrated the same MIC values for all tested strains (0.11 mg/ml, except MIC value against ATCC strain (0.23 mg/ml obtained for Rosemary essential oil. The obtained results indicated that oregano and rosemary essential oils might be highly effective in the natural prevention treatment of candidiasis, although toxicity assays should be previously preformed. [Projekat Ministarstva nauke Republike Srbije, br. 172058

  13. Synthesis and antifungal activity of trichodermin derivatives

    Institute of Scientific and Technical Information of China (English)

    Jing Li Cheng; Yong Zhou; Jin Hao Zhao; Chu Long Zhang; Fu Cheng Lin

    2010-01-01

    A series of derivatives were synthesized from trichodermin(1)which was an antifungal metabolite produced by Trichoderma taxi sp.nov.Their structures were confirmed by 1H NMR,MS spectrum.Their antifungal activities were evaluated in vitro.The preliminary structure activity relationships(SAR)results indicated that the double bond,epoxide moiety and ester group were main pharmacophore elements,the stereochemistry of C4 position played a key role as well,and the compounds 1e-1g displayed stronger antifungal activity against Magnaporthe grisea than 1.

  14. Antifungal isopimaranes from Hypoestes serpens.

    Science.gov (United States)

    Rasoamiaranjanahary, L; Guilet, D; Marston, A; Randimbivololona, F; Hostettmann, K

    2003-09-01

    Five isopimarane diterpenes (7beta-hydroxyisopimara-8,15-dien-14-one, 14alpha-hydroxyisopimara-7,15-dien-1-one, 1beta,14alpha-dihydroxyisopimara-7,15-diene, 7beta-hydroxyisopimara-8(14),15-dien-1-one and 7beta-acetoxyisopimara-8(14),15-dien-1-one) have been isolated from the leaves of Hypoestes serpens (Acanthaceae). All compounds exhibited antifungal activity against both the plant pathogenic fungus Cladosporium cucumerinum and the yeast Candida albicans; two of them also displayed an acetylcholinesterase inhibition. The structures of the compounds were determined by means of spectrometric methods, including 1D and 2D NMR experiments and MS analysis. PMID:12943772

  15. Antifungal properties of halofumarate esters.

    Science.gov (United States)

    Gershon, H; Shanks, L

    1978-04-01

    Alkyl esters (C1--C4) of the four halofumaric acids were tested for antifungal activity against Candida albicans, Aspergillus niger, Mucor mucedo, and Trichophyton mentagrophytes at pH 5.6 and 7.0 in the absence and presence of 10% beef serum in Sabouraud dextrose agar. The most toxic compound to each organism was: C. albicans, ethyl iodofumarate (0.054 mmole/liter); A. niger, methyl bromofumarate (0.090 mmole/liter); M. mucedo, methyl fluorofumarate (0.037 mmole/liter); and T. mentagrophytes, ethyl iodofumarate (0.020 mmole/liter). The order of overall activity of the six most toxic compounds was: ethyl iodofumarate greater than ethyl chlorofumarate greater than methyl iodofumarate = methyl bromofumarate greater than methyl chlorofumarate greater than bromofumarate.

  16. Synthesis, Structure-Activity Relationships (SAR and in Silico Studies of Coumarin Derivatives with Antifungal Activity

    Directory of Open Access Journals (Sweden)

    José M. Barbosa-Filho

    2013-01-01

    Full Text Available The increased incidence of opportunistic fungal infections, associated with greater resistance to the antifungal drugs currently in use has highlighted the need for new solutions. In this study twenty four coumarin derivatives were screened in vitro for antifungal activity against strains of Aspergillus. Some of the compounds exhibited significant antifungal activity with MICs values ranging between 16 and 32 µg/mL. The structure-activity relationships (SAR study demonstrated that O-substitutions are essential for antifungal activity. It also showed that the presence of a short aliphatic chain and/or electron withdrawing groups (NO2 and/or acetate favor activity. These findings were confirmed using density functional theory (DFT, when calculating the LUMO density. In Principal Component Analysis (PCA, two significant principal components (PCs explained more than 60% of the total variance. The best Partial Least Squares Regression (PLS model showed an r2 of 0.86 and q2cv of 0.64 corroborating the SAR observations as well as demonstrating a greater probe N1 interaction for active compounds. Descriptors generated by TIP correlogram demonstrated the importance of the molecular shape for antifungal activity.

  17. Strategies for treating aspergillosis due to azole-resistant Aspergillus fumigatus : from the bench to the bedside

    NARCIS (Netherlands)

    Seyedmousavi Tasieh, S.

    2014-01-01

    In humans, Aspergillus fumigatus is the most common and life-threatening aerial fungal pathogen, especially among immunocompromised patients, with an overall mortality ranging between 30 to 88%. Azole antifungals, such as voriconazole and posaconazole, are recommended first choice drugs to manage as

  18. Synthesis of Pyridazinonethiadiazoles as Possible Antifungal Agents

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Several 5-[1-aryl-1,4-dihydro-6-methylpyridazin-4-one-3-yl]-2-arylamino-1,3,4-thia diazoles were synthesized.The preliminary bio-active test shows that these compounds exhibit high antifungal activity.

  19. Antifungal susceptibility and virulence factors of clinically isolated dermatophytes in Tehran, Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Afshari

    2016-03-01

    Full Text Available Background and Objectives: Dermatophytes possess a wide array of virulence factors and various antifungal susceptibility patterns which influence their pathogenesis in humans and animals. The aim of this study was to evaluate antifungal suscep- tibility and keratinase and proteinase activity of 49 dermatophyte strains from the genera Microsporum, Trichophyton and Epidermophyton which were isolated from human cases of dermatophytosis.Materials and Methods: Forty-nine dermatophyte strains isolated from clinical samples were cultured on general and spe- cific culture media. Keratinase and proteinase activity was screened on solid mineral media and confirmed in liquid cultures. Drug susceptibility toward azoles (fluconazole, ketoconazole and itraconazole, griseofulvin and terbinafine was evaluated using disk diffusion method on Mueller-Hinton agar and minimum inhibitory concentrations (MICs were determined using microbroth dilution assay according to the Clinical and Laboratory Standards Institute (CLSI guidelines.Results: Our results indicated that clinically isolated dermatophytes from 7 major species produced keratinase and protein- ase at different extents. The mean keratinase and proteinase activity was reported as 6.69 ± 0.31 (U/ml and 2.10 ± 0.22 (U/ ml respectively. Disk diffusion and microbroth dilution (MIC results of antifungal susceptibility testing showed that ke- toconazole was the most effective drug against Epidermophyton floccosum and Trichophyton mentagrophytes, itraconazole against T. rubrum and E. floccosum, and griseofulvin and terbinafine against Trichophyton verrucosum. Our results showed that all dermatophyte isolates were resistant to fluconazole. Overall, ketoconazole and itraconazole were the most effective drugs for all dermatophyte species tested.Conclusion: Our results showed that antifungal susceptibility testing is an urgent need to select drugs of choice for treatment of different types of dermatophytosis and

  20. Antifungal activities of some indole derivatives.

    Science.gov (United States)

    Xu, Hui; Wang, Qin; Yang, Wen-Bin

    2010-01-01

    Nine indole derivatives were evaluated in vitro against Fusarium graminearum, Alternaria alternata, Helminthosporium sorokinianum, Pyricularia oryzae, Fusarium oxysporum f. sp. vasinfectum, Fusarium oxysporum f. sp. cucumarinum, and Alternaria brassicae. Most of the compounds were found to possess antifungal activities. Especially compounds 2, 5, 8, and 9 exhibited broad-spectrum antifungal activities against the above-mentioned seven phytopathogenic fungi, and showed more potent activities than hymexazole, a commercial agricultural fungicide. PMID:20737910

  1. Antifungal properties of Brazilian cerrado plants

    Directory of Open Access Journals (Sweden)

    Souza Lúcia Kioko Hasimoto e

    2002-01-01

    Full Text Available Ethanolic extracts from leaves of Hyptis ovalifolia, H. suaveolens, H. saxatilis, Hyptidendrum canum, Eugenia uniflora, E. dysenterica, Caryocar brasiliensis and Lafoensia pacari were investigated for their antifungal activity against dermatophytes. The most effective plants were H. ovalifolia and E. uniflora, while Trichophyton rubrum was the most sensitive among the four dermatophytes species evaluated. This study has demonstrated antifungal properties of Brazilian Cerrado plant extracts in "in vitro" assays.

  2. Antifungal activity of five species of Polygala

    Directory of Open Access Journals (Sweden)

    Susana Johann

    2011-09-01

    Full Text Available Crude extracts and fractions of five species of Polygala - P. campestris, P. cyparissias, P. paniculata, P. pulchella and P. sabulosa - were investigated for their in vitro antifungal activity against opportunistic Candida species, Cryptococcus gattii and Sporothrix schenckii with bioautographic and microdilution assays. In the bioautographic assays, the major extracts were active against the fungi tested. In the minimal concentration inhibitory (MIC assay, the hexane extract of P. paniculata and EtOAc fraction of P. sabulosa showed the best antifungal activity, with MIC values of 60 and 30 µg/mL, respectively, against C. tropicalis, C. gattii and S. schenckii. The compounds isolated from P. sabulosa prenyloxycoumarin and 1,2,3,4,5,6-hexanehexol displayed antifungal activity against S. schenckii (with MICs of 125 µg/mL and 250 µg/mL, respectively and C. gattii (both with MICs of 250 µg/mL. Rutin and aurapten isolated from P. paniculata showed antifungal activity against C. gattii with MIC values of 60 and 250 µg/mL, respectively. In the antifungal screening, few of the isolated compounds showed good antifungal inhibition. The compound α-spinasterol showed broad activity against the species tested, while rutin had the best activity with the lowest MIC values for the microorganisms tested. These two compounds may be chemically modified by the introduction of a substitute group that would alter several physico-chemical properties of the molecule, such as hydrophobicity, electronic density and steric strain.

  3. Antifungal activity of silver nanoparticles in combination with nystatin and chlorhexidine digluconate against Candida albicans and Candida glabrata biofilms.

    Science.gov (United States)

    Monteiro, Douglas R; Silva, Sónia; Negri, Melyssa; Gorup, Luiz F; de Camargo, Emerson R; Oliveira, Rosário; Barbosa, Debora B; Henriques, Mariana

    2013-11-01

    Although silver nanoparticles (SN) have been investigated as an alternative to conventional antifungal drugs in the control of Candida-associated denture stomatitis, the antifungal activity of SN in combination with antifungal drugs against Candida biofilms remains unknown. Therefore, the aim of this study was to evaluate the antifungal efficacy of SN in combination with nystatin (NYT) or chlorhexidine digluconate (CHG) against Candida albicans and Candida glabrata biofilms. The drugs alone or combined with SN were applied on mature Candida biofilms (48 h), and after 24 h of treatment their antibiofilm activities were assessed by total biomass quantification (by crystal violet staining) and colony forming units enumeration. The structure of Candida biofilms was analysed by scanning electron microscopy (SEM) images. The data indicated that SN combined with either NYT or CHG demonstrated synergistic antibiofilm activity, and this activity was dependent on the species and on the drug concentrations used. SEM images showed that some drug combinations were able to disrupt Candida biofilms. The results of this study suggest that the combination of SN with NYT or CHG may have clinical implications in the treatment of denture stomatitis. However, further studies are needed before recommending the use of these drugs safely in clinical situations. PMID:23773119

  4. Drug: D08333 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08333 Drug Pentamidine (INN); Lomidine (TN) C19H24N4O2 340.1899 340.4195 D08333.gif Antiprotozoa...l, leishmanicidal; Antiprotozoal, trypanocidal, Antifungal Same as: C07420 USP drug classifica...tion [BR:br08302] Antiparasitics Antiprotozoals Pentamidine D08333 Pentamidine (INN) CAS: 100-33-4 PubChem:

  5. Antifungal activity of redox-active benzaldehydes that target cellular antioxidation

    Directory of Open Access Journals (Sweden)

    Mahoney Noreen

    2011-05-01

    Full Text Available Abstract Background Disruption of cellular antioxidation systems should be an effective method for control of fungal pathogens. Such disruption can be achieved with redox-active compounds. Natural phenolic compounds can serve as potent redox cyclers that inhibit microbial growth through destabilization of cellular redox homeostasis and/or antioxidation systems. The aim of this study was to identify benzaldehydes that disrupt the fungal antioxidation system. These compounds could then function as chemosensitizing agents in concert with conventional drugs or fungicides to improve antifungal efficacy. Methods Benzaldehydes were tested as natural antifungal agents against strains of Aspergillus fumigatus, A. flavus, A. terreus and Penicillium expansum, fungi that are causative agents of human invasive aspergillosis and/or are mycotoxigenic. The yeast Saccharomyces cerevisiae was also used as a model system for identifying gene targets of benzaldehydes. The efficacy of screened compounds as effective chemosensitizers or as antifungal agents in formulations was tested with methods outlined by the Clinical Laboratory Standards Institute (CLSI. Results Several benzaldehydes are identified having potent antifungal activity. Structure-activity analysis reveals that antifungal activity increases by the presence of an ortho-hydroxyl group in the aromatic ring. Use of deletion mutants in the oxidative stress-response pathway of S. cerevisiae (sod1Δ, sod2Δ, glr1Δ and two mitogen-activated protein kinase (MAPK mutants of A. fumigatus (sakAΔ, mpkCΔ, indicates antifungal activity of the benzaldehydes is through disruption of cellular antioxidation. Certain benzaldehydes, in combination with phenylpyrroles, overcome tolerance of A. fumigatus MAPK mutants to this agent and/or increase sensitivity of fungal pathogens to mitochondrial respiration inhibitory agents. Synergistic chemosensitization greatly lowers minimum inhibitory (MIC or fungicidal (MFC

  6. Antifungal activity of triterpenoid isolated from Azima tetracantha leaves

    International Nuclear Information System (INIS)

    The present study was designed to evaluate the antifungal activity of Azima tetracantha extracts and isolated compound (friedelin) against fungi. Antifungal activity was carried out using broth micro dilution method and fractions were collected using (silica gel) column chromatography. The antifungal activity of Azima tetracantha crude extracts and isolated compound (friedelin) were evaluated using the micro dilution method. Hexane extract showed some antifungal activity. The compound also exhibited antifungal activity against tested fungi. The lowest MIC against Trichophyton rubrum (296) was 62.5 micro g/ml and the MIC for Curvularia lunata was 62.5 micro g/ml. These results suggest that Friedelin is a promising antifungal agent. (authors)

  7. Antifungal activity improved by coproduction of cyclodextrins and anabaenolysins in Cyanobacteria.

    Science.gov (United States)

    Shishido, Tania K; Jokela, Jouni; Kolehmainen, Clara-Theresia; Fewer, David P; Wahlsten, Matti; Wang, Hao; Rouhiainen, Leo; Rizzi, Ermanno; De Bellis, Gianluca; Permi, Perttu; Sivonen, Kaarina

    2015-11-01

    Cyclodextrins are cyclic oligosaccharides widely used in the pharmaceutical industry to improve drug delivery and to increase the solubility of hydrophobic compounds. Anabaenolysins are lipopeptides produced by cyanobacteria with potent lytic activity in cholesterol-containing membranes. Here, we identified the 23- to 24-kb gene clusters responsible for the production of the lipopeptide anabaenolysin. The hybrid nonribosomal peptide synthetase and polyketide synthase biosynthetic gene cluster is encoded in the genomes of three anabaenolysin-producing strains of Anabaena. We detected previously unidentified strains producing known anabaenolysins A and B and discovered the production of new variants of anabaenolysins C and D. Bioassays demonstrated that anabaenolysins have weak antifungal activity against Candida albicans. Surprisingly, addition of the hydrophilic fraction of the whole-cell extracts increased the antifungal activity of the hydrophobic anabaenolysins. The fraction contained compounds identified by NMR as α-, β-, and γ-cyclodextrins, which undergo acetylation. Cyclodextrins have been used for decades to improve the solubility and bioavailability of many drugs including antifungal compounds. This study shows a natural example of cyclodextrins improving the solubility and efficacy of an antifungal compound in an ancient lineage of photosynthetic bacteria.

  8. Soft X-ray tomography of phenotypic switching and the cellular response to antifungal peptoids in Candida albicans

    OpenAIRE

    Uchida, Maho; McDermott, Gerry; Wetzler, Modi; Le Gros, Mark A.; Myllys, Markko; Knoechel, Christian; Barron, Annelise E.; Larabell, Carolyn A.

    2009-01-01

    The opportunistic pathogen Candida albicans can undergo phenotypic switching between a benign, unicellular phenotype and an invasive, multicellular form that causes candidiasis. Increasingly, strains of Candida are becoming resistant to antifungal drugs, making the treatment of candidiasis difficult, especially in immunocompromised or critically ill patients. Consequently, there is a pressing need to develop new drugs that circumvent fungal drug-resistance mechanisms. In this work we used sof...

  9. The in vitro antifungal activity of sudanese medicinal plants against Madurella mycetomatis, the eumycetoma major causative agent.

    Directory of Open Access Journals (Sweden)

    Hassabelrasoul Elfadil

    2015-03-01

    Full Text Available Eumycetoma is a debilitating chronic inflammatory fungal infection that exists worldwide but it is endemic in many tropical and subtropical regions. The major causative organism is the fungus Madurella mycetomatis. The current treatment of eumycetoma is suboptimal and characterized by low cure rate and high recurrence rates. Hence, an alternative therapy is needed to address this. Here we determined the antifungal activity of seven Sudanese medicinal plant species against Madurella mycetomatis. Of these, only three species; Boswellia papyrifera, Acacia nubica and Nigella sativa, showed some antifungal activity against M. mycetomatis and were further studied. Crude methanol, hexane and defatted methanol extracts of these species were tested for their antifungal activity. B. papyrifera had the highest antifungal activity (MIC50 of 1 ug/ml and it was further fractionated. The crude methanol and the soluble ethyl acetate fractions of B. papyrifera showed some antifungal activity. The Gas-Liquid-Chromatography hybrid Mass-Spectrophotometer analysis of these two fractions showed the existence of beta-amyrin, beta-amyrone, beta-Sitosterol and stigmatriene. Stigmatriene had the best antifungal activity, compared to other three phytoconstituents, with an MIC-50 of 32 μg/ml. Although the antifungal activity of the identified phytoconstituents was only limited, the antifungal activity of the complete extracts is more promising, indicating synergism. Furthermore these plant extracts are also known to have anti-inflammatory activity and can stimulate wound-healing; characteristics which might also be of great value in the development of novel therapeutic drugs for this chronic inflammatory disease. Therefore further exploration of these plant species in the treatment of mycetoma is encouraging.

  10. Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids

    Science.gov (United States)

    Mor, Visesato; Rella, Antonella; Farnoud, Amir M.; Singh, Ashutosh; Munshi, Mansa; Bryan, Arielle; Naseem, Shamoon; Konopka, James B.; Ojima, Iwao; Bullesbach, Erika; Ashbaugh, Alan; Linke, Michael J.; Cushion, Melanie; Collins, Margaret; Ananthula, Hari Krishna; Sallans, Larry; Desai, Pankaj B.; Wiederhold, Nathan P.; Fothergill, Annette W.; Kirkpatrick, William R.; Patterson, Thomas; Wong, Lai Hong; Sinha, Sunita; Giaever, Guri; Nislow, Corey; Flaherty, Patrick; Pan, Xuewen; Cesar, Gabriele Vargas; de Melo Tavares, Patricia; Frases, Susana; Miranda, Kildare; Rodrigues, Marcio L.; Luberto, Chiara; Nimrichter, Leonardo

    2015-01-01

    ABSTRACT Recent estimates suggest that >300 million people are afflicted by serious fungal infections worldwide. Current antifungal drugs are static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development of new antifungal drugs. The fungal sphingolipid glucosylceramide (GlcCer) is critical in promoting virulence of a variety of human-pathogenic fungi. In this study, we screened a synthetic drug library for compounds that target the synthesis of fungal, but not mammalian, GlcCer and found two compounds [N′-(3-bromo-4-hydroxybenzylidene)-2-methylbenzohydrazide (BHBM) and its derivative, 3-bromo-N′-(3-bromo-4-hydroxybenzylidene) benzohydrazide (D0)] that were highly effective in vitro and in vivo against several pathogenic fungi. BHBM and D0 were well tolerated in animals and are highly synergistic or additive to current antifungals. BHBM and D0 significantly affected fungal cell morphology and resulted in the accumulation of intracellular vesicles. Deep-sequencing analysis of drug-resistant mutants revealed that four protein products, encoded by genes APL5, COS111, MKK1, and STE2, which are involved in vesicular transport and cell cycle progression, are targeted by BHBM. PMID:26106079

  11. Scedosporium apiospermum infections and the role of combination antifungal therapy and GM-CSF: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Chloe Goldman

    2016-03-01

    Full Text Available Scedosporium apiospermum, a ubiquitous environmental mold, is increasingly reported as causing invasive fungal disease in immunocompromised hosts. It poses a therapeutic challenge due to its intrinsic resistance to traditional antifungals and ability to recur despite demonstrating susceptibility. We present an immunocompromised patient with a cutaneous S. apiospermum infection that disseminated despite treatment with voriconazole, the drug of choice. Adding echinocandins and GM-CSF provided partial recovery, indicating a potential synergistic role of dual-antifungal and immunotherapeutic agents.

  12. Pharmacokinetics and Pharmacodynamics of a Novel Triazole, Isavuconazole: Mathematical Modeling, Importance of Tissue Concentrations, and Impact of Immune Status on Antifungal Effect▿

    OpenAIRE

    Warn, Peter A.; Sharp, Andrew; Parmar, Arvind; Majithiya, Jayesh; David W Denning; Hope, William W.

    2009-01-01

    Isavuconazole is a triazole with broad-spectrum activity against medically important fungal pathogens. We investigated the pharmacokinetics and pharmacodynamics of isavuconazole in a murine model of disseminated candidiasis. We determined the pharmacokinetics in both plasma and kidney. The relationship between tissue concentrations and the resultant antifungal effect was described using a mathematical model. The pharmacodynamic parameter that optimally links drug exposure with the antifungal ...

  13. Structural Basis of Human CYP51 Inhibition by Antifungal Azoles

    Energy Technology Data Exchange (ETDEWEB)

    Strushkevich, Natallia; Usanov, Sergey A.; Park, Hee-Won (Toronto); (IBC-Belarus)

    2010-09-22

    The obligatory step in sterol biosynthesis in eukaryotes is demethylation of sterol precursors at the C14-position, which is catalyzed by CYP51 (sterol 14-alpha demethylase) in three sequential reactions. In mammals, the final product of the pathway is cholesterol, while important intermediates, meiosis-activating sterols, are produced by CYP51. Three crystal structures of human CYP51, ligand-free and complexed with antifungal drugs ketoconazole and econazole, were determined, allowing analysis of the molecular basis for functional conservation within the CYP51 family. Azole binding occurs mostly through hydrophobic interactions with conservative residues of the active site. The substantial conformational changes in the B{prime} helix and F-G loop regions are induced upon ligand binding, consistent with the membrane nature of the protein and its substrate. The access channel is typical for mammalian sterol-metabolizing P450 enzymes, but is different from that observed in Mycobacterium tuberculosis CYP51. Comparison of the azole-bound structures provides insight into the relative binding affinities of human and bacterial P450 enzymes to ketoconazole and fluconazole, which can be useful for the rational design of antifungal compounds and specific modulators of human CYP51.

  14. Antifungal activity from Ocimum gratissimum L. towards Cryptococcus neoformans

    Directory of Open Access Journals (Sweden)

    Janine de Aquino Lemos

    2005-02-01

    Full Text Available Cryptococcal infection had an increased incidence in last years due to the explosion of acquired immune deficiency syndrome epidemic and by using new and effective immunosuppressive agents. The currently antifungal therapies used such as amphotericin B, fluconazole, and itraconazole have certain limitations due to side effects and emergence of resistant strains. So, a permanent search to find new drugs for cryptococcosis treatment is essential. Ocimum gratissimum, plant known as alfavaca (Labiatae family, has been reported earlier with in vitro activity against some bacteria and dermatophytes. In our work, we study the in vitro activity of the ethanolic crude extract, ethyl acetate, hexane, and chloroformic fractions, essential oil, and eugenol of O. gratissimum using an agar dilution susceptibility method towards 25 isolates of Cryptococcus neoformans. All the extracts of O. gratissimum studied showed activity in vitro towards C. neoformans. Based on the minimal inhibitory concentration values the most significant results were obtained with chloroformic fraction and eugenol. It was observed that chloroformic fraction inhibited 23 isolates (92% of C. neoformans at a concentration of 62.5 µg/ml and eugenol inhibited 4 isolates (16% at a concentration of 0.9 µg/ml. This screening may be the basis for the study of O. gratissimum as a possible antifungal agent.

  15. Antifungal activity from Ocimum gratissimum L. towards Cryptococcus neoformans.

    Science.gov (United States)

    Lemos, Janine de Aquino; Passos, Xisto Sena; Fernandes, Orionalda de Fátima Lisboa; Paula, José Realino de; Ferri, Pedro Henrique; Souza, Lúcia Kioko Hasimoto E; Lemos, Aline de Aquino; Silva, Maria do Rosário Rodrigues

    2005-02-01

    Cryptococcal infection had an increased incidence in last years due to the explosion of acquired immune deficiency syndrome epidemic and by using new and effective immunosuppressive agents. The currently antifungal therapies used such as amphotericin B, fluconazole, and itraconazole have certain limitations due to side effects and emergence of resistant strains. So, a permanent search to find new drugs for cryptococcosis treatment is essential. Ocimum gratissimum, plant known as alfavaca (Labiatae family), has been reported earlier with in vitro activity against some bacteria and dermatophytes. In our work, we study the in vitro activity of the ethanolic crude extract, ethyl acetate, hexane, and chloroformic fractions, essential oil, and eugenol of O. gratissimum using an agar dilution susceptibility method towards 25 isolates of Cryptococcus neoformans. All the extracts of O. gratissimum studied showed activity in vitro towards C. neoformans. Based on the minimal inhibitory concentration values the most significant results were obtained with chloroformic fraction and eugenol. It was observed that chloroformic fraction inhibited 23 isolates (92%) of C. neoformans at a concentration of 62.5 microg/ml and eugenol inhibited 4 isolates (16%) at a concentration of 0.9 microg/ml. This screening may be the basis for the study of O. gratissimum as a possible antifungal agent. PMID:15867965

  16. Antifungal activity of triterpenoid isolated from Azima tetracantha leaves.

    OpenAIRE

    Duraipandiyan, V.; M Gnanasekar; S Ignacimuthu

    2010-01-01

    The present study was designed to evaluate the antifungal activity of Azima tetracantha extracts and isolated compound (friedelin) against fungi. Antifungal activity was carried out using broth microdilution method and fractions were collected using (silica gel) column chromatography. The antifungal activity of Azima tetracantha crude extracts and isolated compound (friedelin) were evaluated using the micro dilution method. Hexane extract showed some antifungal activity. The compound also exh...

  17. Design,Synthesis and Antifungal Activity of Novel Triazole Derivatives

    Institute of Scientific and Technical Information of China (English)

    Chun Quan SHENG; Wan Nian ZHANG; Hai Tao JI; Yun Long SONG; Min ZHANG; You Jun ZHOU; Jia Guo LU; Jü ZHU

    2004-01-01

    Twenty-one 1-(1H-1,2,4-triazolyl)-2-(2,4-diflurophenyl)-3-(4-substituted-1- piperazinyl)-2-propanol derivatives were designed and synthesized,on the basis of the active site of lanosterol 14(-demethylase.In vitro antifungal activities showed that some of the target compounds had higher antifungal activity and broader antifungal spectrum than fluconazole.

  18. In vivo application of a small molecular weight antifungal protein of Penicillium chrysogenum (PAF)

    Energy Technology Data Exchange (ETDEWEB)

    Palicz, Zoltán; Jenes, Ágnes; Gáll, Tamás [Department of Physiology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Miszti-Blasius, Kornél [Department of Clinical Biochemistry and Molecular Pathology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Kollár, Sándor; Kovács, Ilona [Department of Pathology, Kenézy Hospital LTD, Debrecen (Hungary); Emri, Miklós; Márián, Teréz [Department of Nuclear Medicine, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Leiter, Éva; Pócsi, István [Department of Microbial Biotechnology and Cell Biology, Faculty of Science and Technology, Centre of Arts, Humanities and Sciences, University of Debrecen, Debrecen (Hungary); Csősz, Éva; Kalló, Gergő [Proteomics Core Facility, Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Hegedűs, Csaba; Virág, László [Department of Medical Chemistry, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Csernoch, László [Department of Physiology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary); Szentesi, Péter, E-mail: szentesi.peter@med.unideb.hu [Department of Physiology, Medical and Health Science Center, University of Debrecen, Debrecen (Hungary)

    2013-05-15

    The antifungal protein of Penicillium chrysogenum (PAF) inhibits the growth of important pathogenic filamentous fungi, including members of the Aspergillus family and some dermatophytes. Furthermore, PAF was proven to have no toxic effects on mammalian cells in vitro. To prove that PAF could be safely used in therapy, experiments were carried out to investigate its in vivo effects. Adult mice were inoculated with PAF intranasally in different concentrations, up to 2700 μg·kg{sup −1} daily, for 2 weeks. Even at the highest concentration – a concentration highly toxic in vitro for all affected molds – used, animals neither died due to the treatment nor were any side effects observed. Histological examinations did not find pathological reactions in the liver, in the kidney, and in the lungs. Mass spectrometry confirmed that a measurable amount of PAF was accumulated in the lungs after the treatment. Lung tissue extracts from PAF treated mice exerted significant antifungal activity. Small-animal positron emission tomography revealed that neither the application of physiological saline nor that of PAF induced any inflammation while the positive control lipopolysaccharide did. The effect of the drug on the skin was examined in an irritative dermatitis model where the change in the thickness of the ears following PAF application was found to be the same as in control and significantly less than when treated with phorbol-12-myristate-13-acetate used as positive control. Since no toxic effects of PAF were found in intranasal application, our result is the first step for introducing PAF as potential antifungal drug in therapy. - Highlights: • PAF, the antifungal protein of Penicillium chrysogenum, was not toxic in mice. • Its intranasal application didn't induce pathological reactions in the lung. • PAF retained its antifungal activity in lung extracts. • Its application on the skin did not cause inflammation.

  19. In vivo application of a small molecular weight antifungal protein of Penicillium chrysogenum (PAF)

    International Nuclear Information System (INIS)

    The antifungal protein of Penicillium chrysogenum (PAF) inhibits the growth of important pathogenic filamentous fungi, including members of the Aspergillus family and some dermatophytes. Furthermore, PAF was proven to have no toxic effects on mammalian cells in vitro. To prove that PAF could be safely used in therapy, experiments were carried out to investigate its in vivo effects. Adult mice were inoculated with PAF intranasally in different concentrations, up to 2700 μg·kg−1 daily, for 2 weeks. Even at the highest concentration – a concentration highly toxic in vitro for all affected molds – used, animals neither died due to the treatment nor were any side effects observed. Histological examinations did not find pathological reactions in the liver, in the kidney, and in the lungs. Mass spectrometry confirmed that a measurable amount of PAF was accumulated in the lungs after the treatment. Lung tissue extracts from PAF treated mice exerted significant antifungal activity. Small-animal positron emission tomography revealed that neither the application of physiological saline nor that of PAF induced any inflammation while the positive control lipopolysaccharide did. The effect of the drug on the skin was examined in an irritative dermatitis model where the change in the thickness of the ears following PAF application was found to be the same as in control and significantly less than when treated with phorbol-12-myristate-13-acetate used as positive control. Since no toxic effects of PAF were found in intranasal application, our result is the first step for introducing PAF as potential antifungal drug in therapy. - Highlights: • PAF, the antifungal protein of Penicillium chrysogenum, was not toxic in mice. • Its intranasal application didn't induce pathological reactions in the lung. • PAF retained its antifungal activity in lung extracts. • Its application on the skin did not cause inflammation

  20. Molecular epidemiology and in-vitro antifungal susceptibility of Aspergillus terreus species complex isolates in Delhi, India: evidence of genetic diversity by amplified fragment length polymorphism and microsatellite typing.

    Directory of Open Access Journals (Sweden)

    Shallu Kathuria

    Full Text Available Aspergillus terreus is emerging as an etiologic agent of invasive aspergillosis in immunocompromised individuals in several medical centers in the world. Infections due to A. terreus are of concern due to its resistance to amphotericin B, in vivo and in vitro, resulting in poor response to antifungal therapy and high mortality. Herein we examined a large collection of molecularly characterized, geographically diverse A. terreus isolates (n = 140 from clinical and environmental sources in India for the occurrence of cryptic A. terreus species. The population structure of the Indian A. terreus isolates and their association with those outside India was determined using microsatellite based typing (STR technique and Amplified Fragment Length Polymorphism analysis (AFLP. Additionally, in vitro antifungal susceptibility of A. terreus isolates was determined against 7 antifungals. Sequence analyses of the calmodulin locus identified the recently described cryptic species A. hortai, comprising 1.4% of Aspergillus section Terrei isolates cultured from cases of aspergilloma and probable invasive aspergillosis not reported previously. All the nine markers used for STR typing of A. terreus species complex proved to be highly polymorphic. The presence of high genetic diversity revealing 75 distinct genotypes among 101 Indian A. terreus isolates was similar to the marked heterogeneity noticed in the 47 global A. terreus population exhibiting 38 unique genotypes mainly among isolates from North America and Europe. Also, AFLP analysis showed distinct banding patterns for genotypically diverse A. terreus isolates. Furthermore, no correlation between a particular genotype and amphotericin B susceptibility was observed. Overall, 8% of the A. terreus isolates exhibited low MICs of amphotericin B. All the echinocandins and azoles (voriconazole, posaconazole and isavuconazole demonstrated high potency against all the isolates. The study emphasizes the need of

  1. Identification of Antifungal Substances of Lactobacillus sakei subsp. ALI033 and Antifungal Activity against Penicillium brevicompactum Strain FI02

    OpenAIRE

    Huh, Chang Ki; Hwang, Tae Yean

    2016-01-01

    This study was performed to investigate the antifungal substances and the antifungal activity against fungi of lactic acid bacteria (LAB) isolated from kimchi. LAB from kimchi in Imsil showed antifungal activity against Penicillium brevicompactum strain FI02. LAB LI031 was identified as Lactobacillus sakei subsp. Antifungal substances contained in L. sakei subsp. ALI033 culture media were unstable at high pH levels. Both, the control and proteinase K and protease treated samples showed clear ...

  2. The novel antifungal agent PLD-118 is neither metabolized by liver microsomes nor inhibits cytochrome P450 in vitro

    NARCIS (Netherlands)

    Parnham, M.J.; Bogaards, J.J.P.; Schrander, F.; Schut, M.W.; Orešković, K.; Mildner, B.

    2005-01-01

    PLD-118 is a novel, oral antifungal drug, under development for the treatment of Candida infections. Possible metabolism of PLD-118 by rat, dog and human S9 liver homogenates and inhibition of human cytochrome P450 (CYP) enzymes were investigated. PLD-118 (10 and 100 μm) incubated for 0-60 min with

  3. In vitro study of the antifungal potential of Lamiaceae hydroalcoholic extracts against Candida species

    OpenAIRE

    Martins, Natália; Ferreira, Isabel C.F.R.; Barros, Lillian; Henriques, Mariana; Silva, Sónia

    2014-01-01

    The use of medicinal plants is an ancient practice, but recently there is an increasing interest towards the evaluation of their bioactive properties. Opportunistic fungal infections, linked with higher rates of fungal resistance to the current antifungal drugs, have deserved special relevance in the last decades. Candida albicans was identified as the main responsible agent for those infections, but other non-Candida albicans Candida (NCAC) species have been also found [1]. Thus,...

  4. In vitro study of the antifungal potential of Apiaceae hydroalcoholic extracts against Candida species

    OpenAIRE

    Martins, Natália; Ferreira, Isabel C.F.R.; Barros, Lillian; Henriques, Mariana; Silva, Sónia Carina

    2014-01-01

    The use of medicinal plants is an ancient practice, but recently there is an increasing interest towards the evaluation of their bioactive properties. Opportunistic fungal infections, linked with higher rates of fungal resistance to the current antifungal drugs, have deserved special relevance in the last decades. Candida albicans was identified as the main responsible agent for those infections, but other non-Candida albicans Candida (NCAC) species have been also found [1]. Thus, it is urgen...

  5. Isolation of a novel antifungal peptide from the bark of Eucommia ulmoides Oliv

    Institute of Scientific and Technical Information of China (English)

    Liu Shihui; Zhao Degang; Han Yuzhen

    2008-01-01

    A novel Eucommia antifungal peptide, named EAFP3, was isolated from the bark of Eucommia ulmoides by NaCl extract, gel filtration and reverse phase high performance liquid chromatography. The molecular mass of EAFP3 is 4157.3 Da, and its partial amino acid sequence is -.LYQQLIAGITLNK.-. EAFP3 exerts an inhibitory activity against Candida albicans in vitro and the drug concentration required for 50% growth inhibition (IC50) is 31.25μg/mL.

  6. Antimicrobial and antifungal activities of Cordia dichotoma (Forster F.) bark extracts.

    Science.gov (United States)

    Nariya, Pankaj B; Bhalodia, Nayan R; Shukla, V J; Acharya, R N

    2011-10-01

    Cordia dichotoma Forst.f. bark, identified as botanical source of Shlesmataka in Ayurvedic pharmacopoeias. Present study was carried out with an objective to investigate the antibacterial and antifungal potentials of Cordia dichotoma bark. Antibacterial activity of methanol and butanol extracts of the bark was carried out against two gram negative bacteria (Escherichia coli, and Pseudomonas aeruginosa) and two Gram positive bacteria (St. pyogenes and Staphylococcus aureus). The antifungal activity of the extracts was carried out against three common pathogenic fungi (Aspergillus niger, A.clavatus, and Candida albicans). Zone of inhibition of extracts was compared with that of different standards like Amplicilline, Ciprofloxacin, Norfloxacin and Chloramphenicol for antibacterial activity and Nystain and Greseofulvin for antifungal activity. The extracts showed remarkable inhibition of zone of bacterial growth and fungal growth and the results obtained were comparable with that of standards drugs against the organisms tested. The activity of extracts increased linearly with increase in concentration of extract (mg/ml). The results showed the antibacterial and antifungal activity against the organisms tested.

  7. In vitro antifungal and antibiofilm activities of halogenated quinoline analogues against Candida albicans and Cryptococcus neoformans.

    Science.gov (United States)

    Zuo, Ran; Garrison, Aaron T; Basak, Akash; Zhang, Peilan; Huigens, Robert W; Ding, Yousong

    2016-08-01

    With the increasing prevalence of fungal infections coupled with emerging drug resistance, there is an urgent need for new and effective antifungal agents. Here we report the antifungal activities of 19 diverse halogenated quinoline (HQ) small molecules against Candida albicans and Cryptococcus neoformans. Four HQ analogues inhibited C. albicans growth with a minimum inhibitory concentration (MIC) of 100 nM, whilst 16 analogues effectively inhibited C. neoformans at MICs of 50-780 nM. Remarkably, two HQ analogues eradicated mature C. albicans and C. neoformans biofilms [minimum biofilm eradication concentration (MBEC) = 6.25-62.5 µM]. Several active HQs were found to penetrate into fungal cells, whilst one inactive analogue was unable to, suggesting that HQs elicit their antifungal activities through an intracellular mode of action. HQs are a promising class of small molecules that may be useful in future antifungal treatments. PMID:27256584

  8. OTYPIC CHARACTERIZATION AND ANTIFUNGAL SUSCEPTIBILITY PATTERN OF CANDIDA SP ISOLATED FROM A TERTIARY CARE CENTER

    Directory of Open Access Journals (Sweden)

    Rudramurthy

    2014-02-01

    Full Text Available ACT: Candida , a yeast like ubiquitous fungus , is an endogenous species which produces commonest fungal infection; Candidiasis. Resistance to antifungal agents is an alarming sign for the emerging common nosocomial candidiasis. MATERIALS AND METHODS: Various types of specimens we re collected from the c linically suspected cases of candidiasis. Isolation and characterization of candida sp . was done by standard procedures. Antifungal susceptibility was done by disc diffusion method. RESULT: The candida was isolated from various clinical specimens , vaginal swab (24.66% , skin scraping (13.33% oral swabs (12.66% , ear swabs ( 11.33% , nail scraping (10% , and pus from diabetes foot ulcer and post - operative wound infection ( 8% , sputum ( 6% , urine (4.66% , stool ( 4% , blood ( 2.66% , and eye swabs ( 2.66%. Amon g different species of candida isolated C.albicans was the predominant species (79.33% followed by C tropicalis (19.33% and C.Guilliermondii (1.33%. Antifungal resistance of different species of candida was higher to fluconazole . The least resistance wa s seen with amphotericin - B (1.33%. CONCLUSION: The increased isolation of candida species and development of resistance to commonly used antifungal drugs requires careful interpretation and the in vitro susceptibility testing. This facilitates better pat ient care.

  9. The research process of the synergistic antifungal effect of plant compositions%植物成分协同抗真菌作用的研究进展

    Institute of Scientific and Technical Information of China (English)

    申玲; 姜远英; 曹永兵

    2013-01-01

    The incidence of systemic fungal infections have increased dramatically in recent years, but now clinically available antifungal drugs are limited, and the research and development of new drugs are difficult. So combination therapy is expected to become the ideal choice for antifungal therapy. Plant compositions can play a synergistic antifungal effect with the antifungal agents in the form of a monomer or mixture. Such research is more extensive and thorough in vitro , but further study on the antifungal effects in vivo , mechanisms and clinical trials is still needed. This review focuses on the antifungal synergism of plant compositions combined with antifungal agents, so as to provide a reference for the study of the novel antifungal drugs.%近年来深部真菌感染的发病率显著上升,而目前临床可用的抗真菌药有限,新药研发难度大,因此联合用药有望成为抗真菌治疗的理想选择.植物成分以单体或混合物的形式与抗真菌药物协同发挥抗真菌的作用,已在体外实验中有比较广泛和深入的研究,但体内抗真菌实验、机制研究和临床试验有待进一步探究.该文就植物成分协同抗真菌作用及其机制的研究进展进行了综述,旨在为新型抗真菌药物的研究提供参考.

  10. In vitro antifungal susceptibility of coelomycete agents of black grain eumycetoma to eight antifungals

    NARCIS (Netherlands)

    Ahmed, Sarah Abdalla; de Hoog, G Sybren; Stevens, David A; Fahal, Ahmed H; van de Sande, Wendy W J

    2015-01-01

    Fungal mycetoma (eumycetoma) represents one of the most difficult infections to appropriately manage. The current recommended treatment is based on extensive surgical debridement combined with prolonged antifungal therapy with ketoconazole or itraconazole. Despite the different phylogenetic position

  11. Formulation and evaluation of Gel containing Fluconazole-Antifungal Agent

    Directory of Open Access Journals (Sweden)

    B. Niyaz Basha

    2011-12-01

    Full Text Available Fluconazole is an imidazole derivative and used for the treatment of local and systemic fungal infection. The oral use of fluconazole is not much recommended as it has many side effects. Commercially fluconazole topical gel preparation are not available in the market, thus this formulation is made for better patient compliance and to reduce the dose of drug and to avoid the side effects like liver damage and kidney damage.. The gel was formulated by changing the polymer ratio. FT-IR study confirmed the purity of drug and revealed no interaction between the drug and excipients. Gel formulations were characterized for drug content, pH determination, viscosity measurement, in vitro diffusion, antifungal activity and skin irritation. Among the five formulations, F1 was selected as the best formulation as its %CDR after 4½ h was 97.846% and release rate of drug from F1 formulation is best fitted to Higuchi model. The viscosity of the F1 formulation was within the limits and F1 formulation did not show any skin irritation. Gel formulation F1 was found to be stable at 30 ±2°C and 65 ± 5 RH. It was found that at 40 ± 2°C and 75 ± 5 RH the gel formulation was not stable and %CDR was decreased. Efficient delivery of drug to skin application was found to be highly beneficial in localizing the drug to desired site in the skin and reduced side effects associated with conventional treatment.

  12. DFT vibrational assignments, in vitro antifungal activity, genotoxic and acute toxicity determinations of the [Zn(phen)2(cnge)(H2O)](NO3)2·H2O complex

    Science.gov (United States)

    Martínez Medina, Juan J.; Torres, Carola A.; Alegre, Walter S.; Franca, Carlos A.; López Tévez, Libertad L.; Ferrer, Evelina G.; Okulik, Nora B.; Williams, Patricia A. M.

    2015-11-01

    Calculations based on density functional methods were carried out for the [Zn(phen)2(cnge)(H2O)](NO3)2·H2O complex taking into account the presence of two different conformers for the cyanoguanidine ligand. The calculated geometrical parameters and the vibrational IR and Raman spectra were in agreement with the experimental data. On the other hand, the activities of the complex, the ligands and the metal against fungal strains have been measured. The complexation increased the antifungal activity of the metal and the ligand cyanoguanidine, and slightly decreased the antifungal activity of the ligand 1,10-phenanthroline against Candida albicans, C. albicans ATCC 10231 and Candida krusei (not against the others strains of Candida). The ligand 1,10-phenanthroline and the zinc complex showed in some cases higher activity than the common antifungal drug fluconazole. The complexation also increased the post-antifungal effect in the tested strains, except for Candida parapsilosis, even with a better efficiency than those of some conventional antifungal agents. Antifungal studies were coupled with safety evaluations using the Artemia salina and the Ames tests. The zinc complex behaved as a non-mutagenic and non-toxic compound at the tested concentrations. Moreover, the zinc complex could be safer than the ligand when used as an antifungal agent. Therefore, the interaction of zinc(II) with N-containing ligands may provide a promising strategy for the development of novel and more secure drugs with antifungal activity.

  13. Synthesis, Antifungal Activities and Qualitative Structure Activity Relationship of Carabrone Hydrazone Derivatives as Potential Antifungal Agents

    OpenAIRE

    Hao Wang; Shuang-Xi Ren; Ze-Yu He; De-Long Wang; Xiao-Nan Yan; Jun-Tao Feng; Xing Zhang

    2014-01-01

    Aimed at developing novel fungicides for relieving the ever-increasing pressure of agricultural production caused by phytopathogenic fungi, 28 new hydrazone derivatives of carabrone, a natural bioactive sesquisterpene, in three types were designed, synthesized and their antifungal activities against Botrytis cinerea and Colletotrichum lagenarium were evaluated. The result revealed that all the derivatives synthesized exhibited considerable antifungal activities in vitro and in vivo, which l...

  14. Impact of New Antifungal Breakpoints on Antifungal Resistance in Candida Species

    OpenAIRE

    Fothergill, Annette W.; Sutton, Deanna A.; McCarthy, Dora I.; Wiederhold, Nathan P.

    2014-01-01

    We reviewed our antifungal susceptibility data for micafungin, anidulafungin, fluconazole, and voriconazole against Candida species and compared resistance rates determined by the previous and recently revised CLSI antifungal breakpoints. With the new breakpoints, resistance was significantly increased for micafungin (from 0.8% to 7.6%), anidulafungin (from 0.9% to 7.3%), and voriconazole (from 6.1% to 18.4%) against Candida glabrata. Resistance was also increased for fluconazole against Cand...

  15. Antifungal prophylaxis during neutropenia and immunodeficiency.

    OpenAIRE

    Lortholary, O; Dupont, B

    1997-01-01

    Fungal infections represent a major source of morbidity and mortality in patients with almost all types of immunodeficiencies. These infections may be nosocomial (aspergillosis) or community acquired (cryptococcosis), or both (candidiasis). Endemic mycoses such as histoplasmosis, coccidioidomycosis, and penicilliosis may infect many immunocompromised hosts in some geographic areas and thereby create major public health problems. With the wide availability of oral azoles, antifungal prophylact...

  16. Antifungal activity of ajoene derived from garlic.

    OpenAIRE

    Yoshida, S.(Department of Physics, Chiba University, 263-8522, Chiba, Japan); Kasuga, S; Hayashi, N; Ushiroguchi, T; Matsuura, H.; Nakagawa, S

    1987-01-01

    The antifungal activity of six fractions derived from garlic was investigated in an in vitro system. Ajoene had the strongest activity in these fractions. The growth of both Aspergillus niger and Candida albicans was inhibited by ajoene at less than 20 micrograms/ml.

  17. Studies of antifungal activity of forsskalea tenacissima

    International Nuclear Information System (INIS)

    Antifungal activity of different extracts from Forsskalea tenacissima prepared by solvent-solvent extraction and vacuum liquid chromatography (VLC) was determined. Extracts were found to be active against Candida albicans, Trichophyton mentagrophyte, Allescheria boydii, Microsporum canis, Aspergillus niger, Drechslera rostrata, Nigrospora oryzae, Stachybotrys atra, Curvularia lunata, Trichophyton semii and Trichophyton schoenleinii. (author)

  18. Meta-Analysis and Cost Comparison of Empirical versus Pre-Emptive Antifungal Strategies in Hematologic Malignancy Patients with High-Risk Febrile Neutropenia.

    Directory of Open Access Journals (Sweden)

    Monica Fung

    Full Text Available Invasive fungal disease (IFD causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN. These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients.We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran's Q test, I2 statistic, and between study τ2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates.Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27-0.85 and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36-1.87 or overall mortality (RR 0.95, 95% CI 0.46-1.99. The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing.Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality

  19. Antifungal susceptibility testing of Candida in the Clinical Laboratory: how to do it, when to do it, and how to interpret it

    Directory of Open Access Journals (Sweden)

    Esther Manso

    2014-06-01

    Full Text Available Significant changes in the management of fungaemia have occurred in the last decade with increased use of fluconazole prophylaxis, of empirical treatment and of echinocandins as first-line agents for documented disease. The emergence of drug resistance in fungal pathogens has a profound impact on human health given limited number of antifungal drugs. Antifungal resistance in Candida may be either intrinsic or acquired and may be encountered in the antifungal drug exposed but also the antifungal drug naïve patient The variation in resistance rates between centers emphasizes that it is essential to have knowledge of the local Candida species distribution and antifungal resistance rates to guide initial therapy for Candida BSI. Moreover, all Candida isolates from blood and normally sterile sites should be identified to the species level. The Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing have developed breakpoints and epidemiological cutoff values that are now established for Candida spp. Clinical microbiology laboratories will be employed commercial susceptibility assays, rather than reference broth microdilution methods and comparative studies are particularly important. Vitek 2®, Etest® and Sensititre YeastOne® provided a high degree of essential agreement and comparable sensitivity and specificity to BMD-RPMI for identifying resistance to azole and echinocandins in Candida spp.

  20. Appropriate use of antifungal agents

    Directory of Open Access Journals (Sweden)

    Elio Castagnola

    2013-07-01

    Full Text Available As knowledge increases faster and faster, authorizations for drug use often don’t report the most recent evidence. In addition, trials on pediatric populations are rare: as a consequence, a lot of drugs in pediatrics are prescribed out of their indications. This is called off-label use, if the drug isn’t approved for the treatment of a specific disease, or unauthorized use, if, for example, a dose isn’t written in the summary of product characteristics. These uses aren’t illegal, but physicians should take some steps in order to protect their liability: for example, the hospital should write documents based on shared scientific evidence, where the reasons supporting a choice are explained. Informed consent should be obtained, after an exhaustive explanation, from the parents. There is also the exceptional use, i.e. the use in desperate cases, where no other treatments are possible, but, for example, a study in an animal model has resulted in good outcomes. Even in this case, similar measures should be taken by the physician.http://dx.doi.org/10.7175/rhc.v4i1S.861

  1. Large-Scale Identification and Analysis of Suppressive Drug Interactions

    OpenAIRE

    Cokol, Murat; Weinstein, Zohar B.; Yilancioglu, Kaan; Tasan, Murat; Doak, Allison; Cansever, Dilay; Mutlu, Beste; Li, Siyang; Rodriguez-Esteban, Raul; Akhmedov, Murodzhon; Guvenek, Aysegul; Cokol, Melike; Cetiner, Selim; Giaever, Guri; Iossifov, Ivan

    2014-01-01

    One drug may suppress the effects of another. Although knowledge of drug suppression is vital to avoid efficacy-reducing drug interactions or discover countermeasures for chemical toxins, drug-drug suppression relationships have not been systematically mapped. Here, we analyze the growth response of Saccharomyces cerevisiae to anti-fungal compound (“drug”) pairs. Among 440 ordered drug pairs, we identified 94 suppressive drug interactions. Using only pairs not selected on the basis of their s...

  2. Large-scale identification and analysis of suppressive drug interactions

    OpenAIRE

    Çokol, Murat; Cokol, Murat; Weinstein, Zohar Bat-El; Yılancıoğlu, Kaan; Yilancioglu, Kaan; Tasan, Murat; Doak, Allison; Cansever, Dilay; Mutlu, Beste; Li, Siyang; Rodriguez-Esteban, Raul; Akhmedov, Murodzhon; Güvenek, Ayşegül; Guvenek, Aysegul; Çokol, Melike

    2014-01-01

    One drug may suppress the effects of another. Although knowledge of drug suppression is vital to avoid efficacy-reducing drug interactions or discover countermeasures for chemical toxins, drug-drug suppression relationships have not been systematically mapped. Here, we analyze the growth response of Saccharomyces cerevisiae to anti-fungal compound ("drug") pairs. Among 440 ordered drub pairs, we identified 94 suppressive drug interactions. Using only pairs not selected on the basis of their s...

  3. 78 FR 35155 - Establishing a List of Qualifying Pathogens Under the Food and Drug Administration Safety and...

    Science.gov (United States)

    2013-06-12

    ... outbreaks of serious bacterial infections caused by Bcc have been documented due to nosocomial transmission... antifungal drugs for the treatment of serious or life-threatening infections, and provides incentives such as... antifungal drugs for the treatment of serious or life-threatening infections. Among other things, it...

  4. 6-O-Branched Oligo-β-glucan-Based Antifungal Glycoconjugate Vaccines.

    Science.gov (United States)

    Liao, Guochao; Zhou, Zhifang; Liao, Jun; Zu, Luning; Wu, Qiuye; Guo, Zhongwu

    2016-02-12

    With the rapid growth in fungal infections and drug-resistant fungal strains, antifungal vaccines have become an especially attractive strategy to tackle this important health problem. β-Glucans, a class of extracellular carbohydrate antigens abundantly and consistently expressed on fungal cell surfaces, are intriguing epitopes for antifungal vaccine development. β-Glucans have a conserved β-1,3-glucan backbone with sporadic β-1,3- or β-1,6-linked short glucans as branches at the 6-O-positions, and the branches may play a critical role in their immunologic functions. To study the immunologic properties of branched β-glucans and develop β-glucan-based antifungal vaccines, three branched β-glucan oligosaccharides with 6-O-linked β-1,6-tetraglucose, β-1,3-diglucose, and β-1,3-tetraglucose branches on a β-1,3-nonaglucan backbone, which mimic the structural epitopes of natural β-glucans, were synthesized and coupled with keyhole limpet hemocyanin (KLH) to form novel synthetic conjugate vaccines. These glycoconjugates were proved to elicit strong IgG antibody responses in mice. It was also discovered that the number, size, and structure of branches linked to the β-glucan backbone had a significant impact on the immunologic property. Moreover, antibodies induced by the synthetic oligosaccharide-KLH conjugates were able to recognize and bind to natural β-glucans and fungal cells. Most importantly, these conjugates elicited effective protection against systemic Candida albicans infection in mice. Thus, branched oligo-β-glucans were identified as functional epitopes for antifungal vaccine design and the corresponding protein conjugates as promising antifungal vaccine candidates. PMID:27624963

  5. Antifungal susceptibility testing of Aspergillus species complex in the Clinical Laboratory: how to do it, when to do it, and how to interpret it

    Directory of Open Access Journals (Sweden)

    Esther Manso

    2014-12-01

    Full Text Available The emergence of drug resistance in fungal pathogens has a profound impact on human health given limited number of antifungal drugs. Antifungal resistance in Aspergillus spp. infection can be encountered in the antifungal drug-exposed patient due to selection of intrinsically resistant species or isolates with acquired resistance belonging to species that are normally susceptible. Resistance to triazoles is not common in Aspergillus spp., however, triazole resistance in A. fumigatus appears to be increasing in several European countries in recent years and can be clinically relevant. The Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing have developed breakpoints and epidemiological cutoff values that are now established for Aspergillus spp. Clinical microbiology laboratories will be employed commercial susceptibility assays, rather than reference broth microdilution methods and comparative studies are particularly important.

  6. Spectrum and the In Vitro Antifungal Susceptibility Pattern of Yeast Isolates in Ethiopian HIV Patients with Oropharyngeal Candidiasis

    Directory of Open Access Journals (Sweden)

    Birhan Moges

    2016-01-01

    Full Text Available Background. In Ethiopia, little is known regarding the distribution and the in vitro antifungal susceptibility profile of yeasts. Objective. This study was undertaken to determine the spectrum and the in vitro antifungal susceptibility pattern of yeasts isolated from HIV infected patients with OPC. Method. Oral pharyngeal swabs taken from oral lesions of study subjects were inoculated onto Sabouraud Dextrose Agar. Yeasts were identified by employing conventional test procedures and the susceptibility of yeasts to antifungal agents was evaluated by disk diffusion assay method. Result. One hundred and fifty-five yeast isolates were recovered of which 91 isolates were from patients that were not under HAART and 64 were from patients that were under HAART. C. albicans was the most frequently isolated species followed by C. glabrata, C. tropicalis, C. krusei, C. kefyr, Cryptococcus laurentii, and Rhodotorula species. Irrespective of yeasts isolated and identified, 5.8%, 5.8%, 12.3%, 8.4%, 0.6%, and 1.3% of the isolates were resistant to amphotericin B, clotrimazole, fluconazole, ketoconazole, miconazole, and nystatin, respectively. Conclusion. Yeast colonization rate of 69.2% and 31% resistance to six antifungal agents was documented. These highlight the need for nationwide study on the epidemiology of OPC and resistance to antifungal drugs.

  7. Phyto chemical Screening, Antibacterial, Antifungal and Anthelmintic Activity of Morinda citrifolia stem

    Directory of Open Access Journals (Sweden)

    Dr. D. Gopala Krishna

    2013-05-01

    Full Text Available In the present study, the Petroleum Ether and Alcoholic extract of Morinda citrifolia L. (Noni stem were subjected to preliminary screening for Antimicrobial and Aanthelmintic activity. The alcoholic extract exhibited significant Anti bacterial, Antifungal activity, comparable to the standard drug Tetracycline. The Petroleum Ether and Alcoholic extract were evaluated for Anthelmintic activity on adult Indian Earthworms, ‘Pheretima posithuma’. The Alcoholic extract produced more significant Anthelmintic activity than Petroleum ether extract and the activities are comparable with the reference drug Piperazine citrate

  8. Drug: D02759 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D02759.gif Antifungal Components: Hexylresorcinol [DR:D04441], Aminoacridine CAS: 7527-91-5 PubChem: 173969...D02759 Drug Acrisorcin (USAN/INN); Akrinol (TN) C12H18O2. C13H10N2 388.2151 388.502

  9. Drug: D07752 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D07752 Drug Croconazole (INN) C18H15ClN2O 310.0873 310.7775 D07752.gif Antifungal; ...7] Imidazoles Croconazole D07752 Croconazole (INN) CAS: 77175-51-0 PubChem: 51092044 LigandBox: D07752 NIKKA

  10. Microdilution procedure for antifungal susceptibility testing of Paracoccidioides brasiliensis to amphotericin b and itraconazole

    Directory of Open Access Journals (Sweden)

    E Takahagi-Nakaira

    2009-01-01

    Full Text Available In vitro tests employing microdilution to evaluate fungal susceptibility to antifungal drugs are already standardized for fermentative yeasts. However, studies on the susceptibility of dimorphic fungi such as Paracoccidioides brasiliensis employing this method are scarce. The present work introduced some modifications into antifungal susceptibility testing from the European Committee on Antimicrobial Susceptibility Testing (EUCAST, concerning broth medium and reading time, to determine minimal inhibitory concentration (MIC of amphotericin B and itraconazole against Paracoccidioides brasiliensis. Yeast-like cells of P. brasiliensis (Pb18 strain were tested for susceptibility to amphotericin B and itraconazole in RPMI 1640 medium, supplemented with 2% glucose and nitrogen source and incubated at 35°C. The MIC of amphotericin B and itraconazole against Pb18 were respectively 0.25 µg/mL and 0.002 µg/mL. The results of minimal fungicidal concentration (MFC showed that amphotericin B at 0.25 µg/mL or higher concentrations displayed fungicidal activity against Pb18 while itraconazole at least 0.002 µg/mL has a fungistatic effect on P. brasiliensis. In conclusion, our results showed that the method employed in the present study is reproducible and reliable for testing the susceptibility of P. brasiliensis to antifungal drugs.

  11. Antifungal Activity of 14-Helical β-Peptides against Planktonic Cells and Biofilms of Candida Species

    Directory of Open Access Journals (Sweden)

    Namrata Raman

    2015-08-01

    Full Text Available Candida albicans is the most prevalent cause of fungal infections and treatment is further complicated by the formation of drug resistant biofilms, often on the surfaces of implanted medical devices. In recent years, the incidence of fungal infections by other pathogenic Candida species such as C. glabrata, C. parapsilosis and C. tropicalis has increased. Amphiphilic, helical β-peptide structural mimetics of natural antimicrobial α-peptides have been shown to exhibit specific planktonic antifungal and anti-biofilm formation activity against C. albicans in vitro. Here, we demonstrate that β-peptides are also active against clinically isolated and drug resistant strains of C. albicans and against other opportunistic Candida spp. Different Candida species were susceptible to β-peptides to varying degrees, with C. tropicalis being the most and C. glabrata being the least susceptible. β-peptide hydrophobicity directly correlated with antifungal activity against all the Candida clinical strains and species tested. While β-peptides were largely ineffective at disrupting existing Candida biofilms, hydrophobic β-peptides were able to prevent the formation of C. albicans, C. glabrata, C. parapsilosis and C. tropicalis biofilms. The broad-spectrum antifungal activity of β-peptides against planktonic cells and in preventing biofilm formation suggests the promise of this class of molecules as therapeutics.

  12. Antifungal Activity of 14-Helical β-Peptides against Planktonic Cells and Biofilms of Candida Species.

    Science.gov (United States)

    Raman, Namrata; Lee, Myung-Ryul; Lynn, David M; Palecek, Sean P

    2015-01-01

    Candida albicans is the most prevalent cause of fungal infections and treatment is further complicated by the formation of drug resistant biofilms, often on the surfaces of implanted medical devices. In recent years, the incidence of fungal infections by other pathogenic Candida species such as C. glabrata, C. parapsilosis and C. tropicalis has increased. Amphiphilic, helical β-peptide structural mimetics of natural antimicrobial α-peptides have been shown to exhibit specific planktonic antifungal and anti-biofilm formation activity against C. albicans in vitro. Here, we demonstrate that β-peptides are also active against clinically isolated and drug resistant strains of C. albicans and against other opportunistic Candida spp. Different Candida species were susceptible to β-peptides to varying degrees, with C. tropicalis being the most and C. glabrata being the least susceptible. β-peptide hydrophobicity directly correlated with antifungal activity against all the Candida clinical strains and species tested. While β-peptides were largely ineffective at disrupting existing Candida biofilms, hydrophobic β-peptides were able to prevent the formation of C. albicans, C. glabrata, C. parapsilosis and C. tropicalis biofilms. The broad-spectrum antifungal activity of β-peptides against planktonic cells and in preventing biofilm formation suggests the promise of this class of molecules as therapeutics. PMID:26287212

  13. Antifungal effects of Zataria multiflora and Nigella sativa extracts against Candida albicans

    Directory of Open Access Journals (Sweden)

    Moghim Hassan

    2015-10-01

    Full Text Available Introduction: Candidiasis is a fungal infection caused by Candida albicans. Recentstudies suggest that the side effects of herbal drugs with significant therapeutic effectsare far less than chemical drugs. This study was therefore, conducted to examineantifungal activities of Zataria multif lora and Nigella sativa extracts on C. albicans.Methods: Powders of Z. multif lora and N. sativa were macerated with ethanol 70% and evaporatedat 38˚C by rotary evaporator. The suspension of C. albicans was prepared according to McFarlandat a concentration of approximately 0.5-2.5 × 10CFU/ml. Testing was performed according tomicrobroth dilution in 96-well micro-dilution plates. Minimum inhibitory concentration (MIC,MIC50%, MIC90% and minimum fungicidal concentration (MFC were separately evaluated bycounting the fungal colonies for Z. multif lora and N. sativa.Results: The measured values of MIC, MIC50%, MIC90% and MFC of Z. multiflora on the C.albicans were 0.13, 0.38, 0.74 and 1.03 mg/ml, and those of N. sativa were 10, 27.7, 52.3 and 72.3 mg/ml, respectively.Conclusion: The results indicate that both Zataria multiflora and Nigella sativa extracts are effectiveagainst Candida albicans, but the former species has the highest antifungal activity. If the clinicaltrials confirm the results of this study, Z. multiflora, as a new antifungal agent by replacing chemicaldrugs can be used to develop antifungal medicinal herbs.

  14. Lamisil, a potent alternative antifungal drug for otomycosis

    Directory of Open Access Journals (Sweden)

    Ali Zarei Mahmoudabadi

    2015-01-01

    Results: Out of 23 isolates of Aspergillus, Candida 4(17.4% and 1(4.4% were resistant to nystatin and miconazole, respectively. In addition, all tested organisms were sensitive to clotrimazole and terbinafine. Statistical analysis has shown that there are no significant differences on the effects of clotrimazole, miconazole and, terbinafine on saprophytic (environmental and pathogenic isolates of A. niger, A. flavus, and A. terreus (P value= 0.85. In addition, all tested organisms were found to be highly susceptible to terbinafine (P< 0.04. Conclusion: This is a new approach for the possible use of Lamisil for the treatment of otomycosis.

  15. Antifungal susceptibilities and identification of species of the Sporothrix schenckii complex isolated in Brazil.

    Science.gov (United States)

    Ottonelli Stopiglia, Cheila Denise; Magagnin, Cibele Massotti; Castrillón, Mauricio Ramírez; Mendes, Sandra Denise Camargo; Heidrich, Daiane; Valente, Patricia; Scroferneker, Maria Lúcia

    2014-01-01

    Sporotrichosis is a subacute or chronic mycosis caused worldwide by the dimorphic species complex, Sporothrix schenckii. We studied 85 isolates recovered in Brazil to verify their identification and evaluate their in vitro antifungal susceptibility patterns. Based on phenotypic tests (microscopic features, ability to grow at 30°C and 37°C, colony diameters, as well as assimilation of sucrose and raffinose) and molecular assays (amplification of a fragment of the calmodulin gene), the strains were identified as S. schenckii, S. brasiliensis and S. globosa, with a predominance of S. schenckii isolates. There was 37.7% disagreement between the phenotypic and genotypic identification methodologies. In general, terbinafine was the most active drug, followed by ketoconazole and itraconazole, and the less active fluconazole and voriconazole. Five isolates (one S. globosa and four S. schenckii) were found to be itraconazole-resistant strains but, in general, there were no differences in the in vitro antifungal susceptibility profiles among the Sporothrix species.

  16. Species distribution & antifungal susceptibility pattern of oropharyngeal Candida isolates from human immunodeficiency virus infected individuals

    Directory of Open Access Journals (Sweden)

    Partha Pratim Das

    2016-01-01

    Results: From the 59 culture positive HIV seropositive cases, 61 Candida isolates were recovered; Candidaalbicans (n=47, 77.0%, C. dubliniensis (n=9, 14.7%, C. parapsilosis (n=2, 3.2%, C. glabrata (n=2, 3.2%, and C. famata (n=1, 1.6%. Candida colonization in HIV-seropositive individuals was significantly higher than that of HIV-seronegative (control group. Antifungal susceptibility testing revealed (n=6, 9.3% C. albicans isolates resistant to voriconazole and fluconazole by disk-diffusion method whereas no resistance was seen by Fungitest method. Interpretation & conclusions: C. albicans was the commonest Candida species infecting or colonizing HIV seropositive individuals. Oropharyngeal Candida isolates had high level susceptibility to all the major antifungals commonly in use. Increased level of immunosuppression in HIV-seropositives and drug resistance of non-albicans Candida species makes identification and susceptibility testing of Candida species necessary in different geographical areas of the country.

  17. Antifungal Agents for the Treatment of Systemic Fungal Infections in Children

    Directory of Open Access Journals (Sweden)

    UD Allen

    2010-01-01

    Full Text Available Traditionally, the mainstay of systemic antifungal therapy has been amphotericin B deoxycholate (conventional amphotericin B. Newer agents have been developed to fulfill special niches and to compete with conventional amphotericin B by virtue of having more favourable toxicity profiles. Some agents have displaced conventional amphotericin B for the treatment of specific fungal diseases. For example, voriconazole has emerged as the preferred treatment for invasive pulmonary aspergillosis. This notwithstanding, conventional amphotericin B remains a useful agent for the treatment of paediatric fungal infections. Knowledge of the characteristics of the newer agents is important, given the increasing numbers of patients who are being treated with these drugs. Efforts need to be directed at research aimed at generating paediatric data where these are lacking. The antifungal agents herein described are most often used as monotherapy regimens because there is no uniform consensus on the value of combination therapy, except for specific scenarios.

  18. Diversity of Bipolaris species in clinical samples in the United States and their antifungal susceptibility profiles.

    Science.gov (United States)

    da Cunha, K C; Sutton, D A; Fothergill, A W; Cano, J; Gené, J; Madrid, H; De Hoog, S; Crous, P W; Guarro, J

    2012-12-01

    A set of 104 isolates from human clinical samples from the United States, morphologically compatible with Bipolaris, were morphologically and molecularly identified through the sequence analysis of the internal transcribed space (ITS) region of the nuclear ribosomal DNA (rDNA). The predominant species was Bipolaris spicifera (67.3%), followed by B. hawaiiensis (18.2%), B. cynodontis (8.6%), B. micropus (2.9%), B. australiensis (2%), and B. setariae (1%). Bipolaris cynodontis, B. micropus, and B. setariae represent new records from clinical samples. The most common anatomical sites where isolates were recovered were the nasal region (30.7%), skin (19.2%), lungs (14.4%), and eyes (12.5%). The antifungal susceptibilities of 5 species of Bipolaris to 9 drugs are provided. With the exception of fluconazole and flucytosine, the antifungals tested showed good activity. PMID:23052310

  19. ANTIFUNGAL ACTIVITIES OF CUNNINGHAMIA LANCEOLATA HEARTWOOD EXTRACTIVES

    Directory of Open Access Journals (Sweden)

    Jing Wang

    2011-02-01

    Full Text Available Three extractives from China-fir were obtained by a sequential extraction processes with hexane, ethyl acetate, and methanol. The components of the three extractives were analyzed: (1 The gas chromatography-mass spectrometry (GC-MS analysis showed that in addition to the presence of cedrol, naphthalenes comprised a relatively large percentage of both the hexane extract (10.39% and the ethyl acetate extract (9.43%. (2 Total phenolic contents analysis showed that phenols took up 6.66 % of the ethyl acetate extract and 22.8% of the methanol extract. All extracts, even with low concentrations, presented fair antifungal activities against two white-rot fungi, Trametes versicolor and Irpex lacteus and two brown-rot fungi, Postia placenta and Gloeophyllum trabeum. Cedrol and naphthalenes were partly responsible for the bioactivities. The synergistic effect of phenols and antifungal compounds also contributed to the wood decay resistance.

  20. Antifungal activity of 10 Guadeloupean plants.

    Science.gov (United States)

    Biabiany, Murielle; Roumy, Vincent; Hennebelle, Thierry; François, Nadine; Sendid, Boualem; Pottier, Muriel; Aliouat, El Moukhtar; Rouaud, Isabelle; Lohézic-Le Dévéhat, Françoise; Joseph, Henry; Bourgeois, Paul; Sahpaz, Sevser; Bailleul, François

    2013-11-01

    Screening of the antifungal activities of ten Guadeloupean plants was undertaken to find new extracts and formulations against superficial mycoses such as onychomycosis, athlete's foot, Pityriasis versicolor, as well as the deep fungal infection Pneumocystis pneumonia. For the first time, the CMI of these plant extracts [cyclohexane, ethanol and ethanol/water (1:1, v/v)] was determined against five dermatophytes, five Candida species, Scytalidium dimidiatum, a Malassezia sp. strain and Pneumocystis carinii. Cytotoxicity tests of the most active extracts were also performed on an HaCat keratinocyte cell line. Results suggest that the extracts of Bursera simaruba, Cedrela odorata, Enterolobium cyclocarpum and Pluchea carolinensis have interesting activities and could be good candidates for developing antifungal formulations. PMID:23280633

  1. A new antifungal coumarin from Clausena excavata.

    Science.gov (United States)

    Kumar, Ramashish; Saha, Aniruddha; Saha, Dipanwita

    2012-01-01

    A new γ-lactone coumarin, named as excavarin-A, showing antifungal activity was isolated from the leaves of Clausena excavata by bioassay guided fractionation method. The structure was elucidated by spectroscopic data analysis and identified as 7((2E)-4(4,5-dihydro-3-methylene-2-oxo-5-furanyl)-3-methylbut-2-enyloxy) coumarin. Minimum inhibitory concentration (MIC) was determined against fifteen fungal strains pathogenic against plants and human. The least MIC was recorded against the human pathogen, Candida tropicalis and the plant pathogens Rhizoctonia solani and Sclerotinia sclerotiorum. Antifungal activities against the human pathogens, Aspergillus fumigatus and Mucor circinelloides and plant pathogens, Colletotrichum gloeosporioides, Lasiodiplodia theobromae, Fusarium oxysporum and Rhizopus stolonifer were stronger than that of the standard antimicrobials. PMID:22088496

  2. Antibacterial, Antifungal and antioxidant activities of some medicinal plants.

    Science.gov (United States)

    Wazir, Asma; Mehjabeen, -; Jahan, Noor; Sherwani, Sikander Khan; Ahmad, Mansoor

    2014-11-01

    The purpose of this study was to evaluate the antibacterial, antifungal and antioxidant activities of medicinal plants. The antibacterial activity of methanolic extracts of three medicinal plants (Swertia chirata, Terminalia bellerica and Zanthoxylum armatum) were tested against Gentamicin (standard drug) on eleven gram positive and seventeen gram negative bacteria by agar well method. It was revealed that seven-gram negative and six gram positive bacterial species were inhibited by these plant extracts. Minimum inhibitory concentrations (MIC) of the extracts were determined by broth micro-dilution method. The significant MIC value of Swertia chirata was 20mg/ml against Serratia marcesens, Zanthoxylum armatum was 10 mg/ml against Aeromonas hydrophila and Terminali bellerica was 20mg/ml against Acinetobacter baumanii as well as Serratia marcesens. Antifungal screening was done for methanolic extracts of these plants by agar well method with the 6 saprophytic, 5 dermatophytic and 6 yeasts. In this case Griseofulvin was used as a standard. All saprophytes and dermatophytes were showed resistance by these plants extracts except Microsporum canis, which was inhibited by Z. armatum and S. chirata extracts. The significant MIC value of Zanthoxylum armatum was 10mg/ml against Microsporum canis and Swertia chirata was 10mg/ml against Candida tropicalis. The anti-oxidant study was performed by DPPH free radical scavenging assay using ascorbic acid as a reference standard. Significant antioxidant activities were observed by Swertia chirata and Zanthoxylum armatum at concentration 200μg/ml was 70% DPPH scavenging activity (EC50=937.5μg/ml) while Terminalia bellerica showed 55.6% DPPH scavenging activity (EC50=100μg/ml). This study has shown that these plants could provide potent antibacterial compounds and may possible preventive agents in ROS related ailments. PMID:26045377

  3. Drug-induced hair loss.

    Science.gov (United States)

    2016-05-01

    Hair loss can have major psychological consequences. It can be due to a wide variety of causes, including hormonal disorders, dietary factors, infections, inflammation, trauma, emotional factors, and cancer. Drugs can also induce hair loss, by interacting with the hair growth cycle. Drug-induced hair loss may be immediate or delayed, sudden or gradual, and diffuse or localised. It is usually reversible after drug discontinuation. The drugs most often implicated in hair loss are anticancer agents, interferon, azole antifungals, lithium, immunosuppressants, and many other drugs belonging to a variety of pharmacological classes.

  4. ANTIFUNGAL ACTIVITY OF CORALLOCARPUS EPIGAEUS (HOOK. F.)

    OpenAIRE

    Vasantha K; Mohan V R

    2012-01-01

    In the present study, petroleum ether, hexane, chloroform, acetone and methanol extracts of leaf, stem and tuber of C. epigaeus were investigated for antifungal activity against Candida albicans, C. tropicalis, Aspergillus niger, A. flavus and A. versicolor by disc diffusion method. Methanol extract of C. epigaeus tuber exhibited maximum activity against most of the tested fungi. The petroleum ether and hexane extracts obtained from C. epigaeus stem was found to be active only against A. nige...

  5. Metabolic footprinting for investigation of antifungal properties of Lactobacillus paracasei

    DEFF Research Database (Denmark)

    Honoré, Anders Hans; Aunsbjerg, Stina Dissing; Ebrahimi, Parvaneh;

    2016-01-01

    footprinting proved to be a supplement to bioassay-guided fractionation for investigation of antifungal properties of bacterial ferments. Additionally, three previously identified and three novel antifungal metabolites from Lb. paracasei and their potential precursors were detected and assigned using......Lactic acid bacteria with antifungal properties are applied for biopreservation of food. In order to further our understanding of their antifungal mechanism, there is an ongoing search for bioactive molecules. With a focus on the metabolites formed, bioassay-guided fractionation and comprehensive...... screening have identified compounds as antifungal. Although these are active, the compounds have been found in concentrations that are too low to account for the observed antifungal effect. It has been hypothesized that the formation of metabolites and consumption of nutrients during bacterial fermentations...

  6. Large-scale identification and analysis of suppressive drug interactions.

    Science.gov (United States)

    Cokol, Murat; Weinstein, Zohar B; Yilancioglu, Kaan; Tasan, Murat; Doak, Allison; Cansever, Dilay; Mutlu, Beste; Li, Siyang; Rodriguez-Esteban, Raul; Akhmedov, Murodzhon; Guvenek, Aysegul; Cokol, Melike; Cetiner, Selim; Giaever, Guri; Iossifov, Ivan; Nislow, Corey; Shoichet, Brian; Roth, Frederick P

    2014-04-24

    One drug may suppress the effects of another. Although knowledge of drug suppression is vital to avoid efficacy-reducing drug interactions or discover countermeasures for chemical toxins, drug-drug suppression relationships have not been systematically mapped. Here, we analyze the growth response of Saccharomyces cerevisiae to anti-fungal compound ("drug") pairs. Among 440 ordered drug pairs, we identified 94 suppressive drug interactions. Using only pairs not selected on the basis of their suppression behavior, we provide an estimate of the prevalence of suppressive interactions between anti-fungal compounds as 17%. Analysis of the drug suppression network suggested that Bromopyruvate is a frequently suppressive drug and Staurosporine is a frequently suppressed drug. We investigated potential explanations for suppressive drug interactions, including chemogenomic analysis, coaggregation, and pH effects, allowing us to explain the interaction tendencies of Bromopyruvate. PMID:24704506

  7. Antifungal ellagitannin isolated from Euphorbia antisyphilitica Zucc

    Institute of Scientific and Technical Information of China (English)

    Juan Ascacio-Valds; Edgardo Burboa; Antonio F Aguilera-Carbo; Mario Aparicio; Ramn Prez-Schmidt; Ral Rodrguez; Cristbal N Aguilar

    2013-01-01

    Objective: To study antifungal activity of a new ellagitannin isolated from the plant residues of Euphorbia antisyphilitica (E. antisyphilitica) Zucc in the wax extraction process. Methods:An extract was prepared from dehydrated and pulverized residues and fractionated by liquid chromatography on Amberilte XAD-16, until obtained an ellagitannin-rich ethanolic fraction which was treated by rotaevaporation to recover the ellagitannin as fine powder. An aqueous solution was prepared and treated through ionic exchange liquid chromatography (Q XL) and gel permeation chromatography (G 25). The ellagitannin-rich fraction was thermogravimetrically evaluated (TGA and DTA) to test the thermo-stability of ellagic acid (monomeric unit). Then ellagitannin powder was analyzed by infrared spectrospcopy to determinate the functional groups and, also mass spectroscopy was used to determine the molecular ion. Results: The principal functional groups of ellagitannin were determined, the molecular weight was 860.7 g/mol; and an effective antifungal activity against phytopathogenic fungi was demonstrated. Conclusions: It can be concluded that the new ellagitannin (860.7 g/mol) isolated from E. antisyphilitica Zucc is an effective antifungal agent against Alternaria alternata, Fusarium oxyzporum, Colletotrichum gloeosporoides and Rhizoctnia solani.

  8. Antifungal ellagitannin isolated from Euphorbia antisyphilitica Zucc

    Institute of Scientific and Technical Information of China (English)

    Juan; Ascacio-Valdés; Edgardo; Burboa; Antonio; F; Aguilera-Carbo; Mario; Aparicio; Ramón; Pérez-Schmidt; Raúl; Rodríguez; Cristóbal; N; Aguilar

    2013-01-01

    Objective:To study antifungal activity of a new ellagitannin isolated from the plant residues of Euphorbia antisyphilitica(E.antisyphilitica)Zucc in the wax extraction process.Methods:An extract was prepared from dehydrated and pulverized residues and fractionated by liquid chromatography on Amberilte XAD-16,until obtained an ellagitannin-rich ethanolic fraction which was treated by rotaevaporation to recover the ellagitannin as fine powder.An aqueous solution was prepared and treated through ionic exchange liquid chromatography(Q XL)and gel permeation chromatography(G 25).The ellagitannin-rich fraction was thermogravimetrically evaluated(TGA and DTA)to test the thermo-stability of ellagic acid(monomeric unit).Then ellagitannin powder was analyzed by infrared spectrospcopy to determinate the functional groups and.also mass spectroscopy was used to determine the molecular ion.Results:The principal functional groups of ellagitannin were determined,the molecular weight was 860.7 g/mol;and an effective antifungal activity against phytopathogenic fungi was demonstrated.Conclusions:It can be concluded that the new ellagitannin(860.7 g/mol)isolated from E.antisyphilitica Zucc is an effective antifungal agent against Alternaria alternata,Fusarium oxyzporum,Colletotrichum gloeosporoides and Rhizoctnia solani.

  9. Antifungal activity of Terminalia superba (combretaceae

    Directory of Open Access Journals (Sweden)

    SIAKA Sohro

    2015-04-01

    Full Text Available The aim of the present study was to optimize the anticandidosic activities of Terminalia superba (TEKAM4 and the identification of major compounds present in the most active chromatographic fraction. The hydroethanolic extract TEKAM4-X0 was prepared by homogenization employing a blender. Two derivatives extracts of TEKAM4-X0 (X1-1 and X1-2 were obtained by a liquid/liquid partition of TEKAM4-X0 in a mixture of hexane and water (v/v. Three chromatographic fractions (F1, F2 and F3 from X1-2 were separated by means of Sephadex-LH20 gel filtration chromatography. All the extracts were incorporated to Sabouraud according to the agar slanted double dilution method. Ketoconazole was used as standards for antifungal assay. The entire fractions were tested on the previously prepared medium culture containing 1000 cells of C. albicans. Antifungal activity was determined by evaluating antifungal parameters values (MFC and IC50. Lastly, the structures of 2 isolated compounds were elucidated by combination of Flash chromatography and spectroscopic methods, including MS, and multiple stage RMN experiments.

  10. Antifungal Efficacy of Myrtus communis Linn

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    Sadeghi Nejad

    2014-08-01

    Full Text Available Background The ethanolic extract of Myrtus communis Linn. leaves was assayed in vitro as a growth inhibitor against opportunistic fungi such as Candida and Aspergillus species. Myrtus communis Linn. (Family, Myrtaceae is an aromatic evergreen shrub or small tree. It is native to the Mediterranean region. Objectives This study aimed to assess antifungal activity (in vitro of the ethanolic extracts of Myrtus communis leaves as a growth inhibitor against 24 clinical isolates of Candida, including C. albicans, C. glabrata, and C. tropicalis also three species of Aspergillus, including A. niger, A. flavus, and A. terreus. Materials and Methods The ethanolic extract of myrtle leaves was prepared by maceration method and minimal inhibitory concentration (MIC of Myrtus communis leaves extract was determined by agar-well diffusion technique. Amphotericin B and clotrimazole were used as the positive control in this assay. Results The minimal inhibitory concentration (MICs values of Myrtus communis leaves extract ranged 0.625-5.0 µg/µL and 5-40 µg/µL against tested Candida spp. and Aspergillus spp., respectively. Conclusions Results revealed that the ethanolic extract of Myrtus communis leaves have antifungal potency against both pathogenic tested fungi, and it can be used as a natural antifungal agent.

  11. Use of the Aspergillus oryzae actin gene promoter in a novel reporter system for exploring antifungal compounds and their target genes.

    Science.gov (United States)

    Marui, Junichiro; Yoshimi, Akira; Hagiwara, Daisuke; Fujii-Watanabe, Yoshimi; Oda, Ken; Koike, Hideaki; Tamano, Koichi; Ishii, Tomoko; Sano, Motoaki; Machida, Masayuki; Abe, Keietsu

    2010-08-01

    Demand for novel antifungal drugs for medical and agricultural uses has been increasing because of the diversity of pathogenic fungi and the emergence of drug-resistant strains. Genomic resources for various living species, including pathogenic fungi, can be utilized to develop novel and effective antifungal compounds. We used Aspergillus oryzae as a model to construct a reporter system for exploring novel antifungal compounds and their target genes. The comprehensive gene expression analysis showed that the actin-encoding actB gene was transcriptionally highly induced by benomyl treatment. We therefore used the actB gene to construct a novel reporter system for monitoring responses to cytoskeletal stress in A. oryzae by introducing the actB promoter::EGFP fusion gene. Distinct fluorescence was observed in the reporter strain with minimum background noise in response to not only benomyl but also compounds inhibiting lipid metabolism that is closely related to cell membrane integrity. The fluorescent responses indicated that the reporter strain can be used to screen for lead compounds affecting fungal microtubule and cell membrane integrity, both of which are attractive antifungal targets. Furthermore, the reporter strain was shown to be technically applicable for identifying novel target genes of antifungal drugs triggering perturbation of fungal microtubules or membrane integrity.

  12. Mechanisms of the antifungal action of marine metagenome-derived peptide, MMGP1, against Candida albicans.

    Directory of Open Access Journals (Sweden)

    Muthuirulan Pushpanathan

    Full Text Available BACKGROUND: Development of resistant variants to existing antifungal drugs continues to be the serious problem in Candida albicans-induced fungal pathogenesis, which has a considerable impact on animal and human health. Identification and characterization of newer drugs against C. albicans is, therefore, essential. MMGP1 is a direct cell-penetrating peptide recently identified from marine metagenome, which was found to possess potent antifungal activity against C. albicans. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the mechanism of antifungal action of MMGP1 against C. albicans. Agarose gel shift assay found the peptide to be having a remarkable DNA-binding ability. The modification of the absorption spectra and fluorescence quenching of the tryptophyl residue correspond to the stacking between indole ring and nucleotide bases. The formation of peptide-DNA complexes was confirmed by fluorescence quenching of SYTO 9 probe. The interaction of peptide with plasmid DNA afforded protection of DNA from enzymatic degradation by DNase I. In vitro transcription of mouse β-actin gene in the presence of peptide led to a decrease in the level of mRNA synthesis. The C. albicans treated with MMGP1 showed strong inhibition of biosynthetic incorporation of uridine analog 5-ethynyluridine (EU into nascent RNA, suggesting the peptide's role in the inhibition of macromolecular synthesis. Furthermore, the peptide also induces endogenous accumulation of reactive oxygen species (ROS in C. albicans. MMGP1 supplemented with glutathione showed an increased viability of C. albicans cells. The hyper-produced ROS by MMGP1 leads to increased levels of protein carbonyls and thiobarbituric acid reactive substances and it also causes dissipation of mitochondrial membrane potential and DNA fragmentation in C. albicans cells. CONCLUSION: And Significance: Therefore, the antifungal activity of MMGP1 could be attributed to its binding with DNA, causing

  13. Synthetic arylquinuclidine derivatives exhibit antifungal activity against Candida albicans, Candida tropicalis and Candida parapsilopsis

    Directory of Open Access Journals (Sweden)

    Gilbert Ian

    2011-01-01

    Full Text Available Abstract Background Sterol biosynthesis is an essential pathway for fungal survival, and is the biochemical target of many antifungal agents. The antifungal drugs most widely used to treated fungal infections are compounds that inhibit cytochrome P450-dependent C14α-demethylase (CYP51, but other enzymes of this pathway, such as squalene synthase (SQS which catalyses the first committed step in sterol biosynthesis, could be viable targets. The aim of this study was to evaluate the antifungal activity of SQS inhibitors on Candida albicans, Candida tropicalis and Candida parapsilopsis strains. Methods Ten arylquinuclidines that act as SQS inhibitors were tested as antiproliferative agents against three ATCC strains and 54 clinical isolates of Candida albicans, Candida tropicalis and Candida parapsilopsis. Also, the morphological alterations induced in the yeasts by the experimental compounds were evaluated by fluorescence and transmission electron microscopy. Results The most potent arylquinuclidine derivative (3-[1'-{4'-(benzyloxy-phenyl}]-quinuclidine-2-ene (WSP1267 had a MIC50 of 2 μg/ml for all species tested and MIC90 varying from 4 μg/ml to 8 μg/ml. Ultrathin sections of C. albicans treated with 1 μg/ml of WSP1267 showed several ultrastructural alterations, including (a loss of cell wall integrity, (b detachment of the plasma membrane from the fungal cell wall, (c accumulation of small vesicles in the periplasmic region, (d presence of large electron-dense vacuoles and (e significantly increased cell size and cell wall thickness. In addition, fluorescence microscopy of cells labelled with Nile Red showed an accumulation of lipid droplets in the cytoplasm of treated yeasts. Nuclear staining with DAPI revealed the appearance of uncommon yeast buds without a nucleus or with two nuclei. Conclusion Taken together, our data demonstrate that arylquinuclidine derivatives could be useful as lead compounds for the rational synthesis of new

  14. Preformed antifungal compounds in strawberry fruit and flower tissues

    OpenAIRE

    Terry, Leon A.; Joyce, Daryl C.; Adikaram, Nimal K. B.; Khambay, Bhupinder P. S.

    2004-01-01

    Antifungal activity against the pathogen, Botrytis cinerea, and a bioassay organism, Cladosporium cladosporioides, declined with advancing strawberry fruit maturity as shown by thin layer chromatography (TLC) bioassays. Preformed antifungal activity was also present in flower tissue. The fall in fruit antifungal compounds was correlated with a decline in natural disease resistance (NDR) against B. cinerea in-planta. Crude extracts of green stage I fruit (7 days after anthesi...

  15. Design, synthesis and antifungal activity of novel triazole derivatives

    Institute of Scientific and Technical Information of China (English)

    Qing lie Zhao; Yan Song; Hong Gang Hu; Shi Chong Yu; Qiu Ye Wu

    2007-01-01

    Twenty-three 1 -(1H-1,2,4-triazole-1-yl)-2-(2,4-difluorophenyl)-3-(N-cycloproyl-N-substituted-amino)-2-propanols were designed and synthesized on the basis of the active site of lanosterol 14α-demethylase.In vitro antifungal activities showed that some of the title compounds had higher antifungal activity and broader antifungal spectrum than fluconazole.

  16. Antifungal Susceptibility Testing of Ascomycetous Yeasts Isolated from Animals.

    Science.gov (United States)

    Álvarez-Pérez, Sergio; García, Marta E; Peláez, Teresa; Martínez-Nevado, Eva; Blanco, José L

    2016-08-01

    Recent studies suggest that antifungal resistance in yeast isolates of veterinary origin may be an underdiagnosed threat. We tested a collection of 92 ascomycetous yeast isolates that were obtained in Spain from birds, mammals and insects for antifungal susceptibility. MICs to amphotericin B and azoles were low, and no resistant isolates were detected. Despite these results, and given the potential role of animals as reservoirs of resistant strains, continuous monitoring of antifungal susceptibility in the veterinary setting is recommended. PMID:27216048

  17. Factors predicting prolonged empirical antifungal treatment in critically ill patients

    OpenAIRE

    Zein, Mohamed; Parmentier-Decrucq, Erika; Kalaoun, Amer; Bouton, Olivier; Wallyn, Frédéric; Baranzelli, Anne; Elmanser, Dia; Sendid, Boualem; Nseir, Saad

    2014-01-01

    Objective To determine the incidence, risk factors, and impact on outcome of prolonged empirical antifungal treatment in ICU patients. Methods Retrospective observational study performed during a one-year period. Patients who stayed in the ICU >48 h, and received empirical antifungal treatment were included. Patients with confirmed invasive fungal disease were excluded. Prolonged antifungal treatment was defined as percentage of days in the ICU with antifungals > median percentage in the whol...

  18. ANTIFUNGAL ACTIVITY OF SOME COLEUS SPECIES GROWING IN NILGIRIS

    OpenAIRE

    P Nilani; Duraisamy, B.; Dhanabal, P.S.; khan, Saleemullah; Suresh, B.; Shankar, V; Kavitha, K.Y.; Syamala, G.

    2006-01-01

    The in vitro antifungal activity of solvent extracts of Coleus forskohlii, Coleus blumei and Coleus barbatus were compared by testing against some pathogenic fungi like Aspergillus niger, Aspergillus fumigatus, Aspergillus ruantii, Proteus vulgaris and Candida albicans. The petroleum ether extract of Coleus forskohlii and Coleus barbatus exhibited significant antifungal activity against all the selected organisms. The extracts of Coleus blumei did not show any significant antifungal activity ...

  19. Candidaemia and antifungal therapy in a French University Hospital: rough trends over a decade and possible links

    Directory of Open Access Journals (Sweden)

    Standaert Annie

    2006-05-01

    Full Text Available Abstract Background Evidence for an increased prevalence of candidaemia and for high associated mortality in the 1990s led to a number of different recommendations concerning the management of at risk patients as well as an increase in the availability and prescription of new antifungal agents. The aim of this study was to parallel in our hospital candidemia incidence with the nature of prescribed antifungal drugs between 1993 and 2003. Methods During this 10-year period we reviewed all cases of candidemia, and collected all the data about annual consumption of prescribed antifungal drugs Results Our centralised clinical mycology laboratory isolates and identifies all yeasts grown from blood cultures obtained from a 3300 bed teaching hospital. Between 1993 and 2003, 430 blood yeast isolates were identified. Examination of the trends in isolation revealed a clear decrease in number of yeast isolates recovered between 1995–2000, whereas the number of positive blood cultures in 2003 rose to 1993 levels. The relative prevalence of Candida albicans and C. glabrata was similar in 1993 and 2003 in contrast to the period 1995–2000 where an increased prevalence of C. glabrata was observed. When these quantitative and qualitative data were compared to the amount and type of antifungal agents prescribed during the same period (annual mean defined daily dose: 2662741; annual mean cost: 615629 € a single correlation was found between the decrease in number of yeast isolates, the increased prevalence of C. glabrata and the high level of prescription of fluconazole at prophylactic doses between 1995–2000. Conclusion Between 1993 and 2000, the number of cases of candidemia halved, with an increase of C. glabrata prevalence. These findings were probably linked to the use of Fluconazole prophylaxis. Although it is not possible to make any recommendations from this data the information is nevertheless interesting and may have considerable implications with

  20. Potato Dextrose Agar Antifungal Susceptibility Testing for Yeasts and Molds: Evaluation of Phosphate Effect on Antifungal Activity of CMT-3

    OpenAIRE

    Liu, Yu; Tortora, George; Ryan, Maria E.; Lee, Hsi-Ming; Lorne M. Golub

    2002-01-01

    The broth macrodilution method (BMM) for antifungal susceptibility testing, approved by the National Committee for Clinical Laboratory Standards (NCCLS), was found to have deficiencies in testing of the antifungal activity of a new type of antifungal agent, a nonantibacterial chemically modified tetracycline (CMT-3). The high content of phosphate in the medium was found to greatly increase the MICs of CMT-3. To avoid the interference of phosphate in the test, a new method using potato dextros...

  1. Antifungal activity of extracts from Atacama Desert fungi against Paracoccidioides brasiliensis and identification of Aspergillus felis as a promising source of natural bioactive compounds.

    Science.gov (United States)

    Mendes, Graziele; Gonçalves, Vívian N; Souza-Fagundes, Elaine M; Kohlhoff, Markus; Rosa, Carlos A; Zani, Carlos L; Cota, Betania B; Rosa, Luiz H; Johann, Susana

    2016-03-01

    Fungi of the genus Paracoccidioides are responsible for paracoccidioidomycosis. The occurrence of drug toxicity and relapse in this disease justify the development of new antifungal agents. Compounds extracted from fungal extract have showing antifungal activity. Extracts of 78 fungi isolated from rocks of the Atacama Desert were tested in a microdilution assay against Paracoccidioides brasiliensis Pb18. Approximately 18% (5) of the extracts showed minimum inhibitory concentration (MIC) values ≤ 125.0 µg/mL. Among these, extract from the fungus UFMGCB 8030 demonstrated the best results, with an MIC of 15.6 µg/mL. This isolate was identified as Aspergillus felis (by macro and micromorphologies, and internal transcribed spacer, β-tubulin, and ribosomal polymerase II gene analyses) and was grown in five different culture media and extracted with various solvents to optimise its antifungal activity. Potato dextrose agar culture and dichloromethane extraction resulted in an MIC of 1.9 µg/mL against P. brasiliensis and did not show cytotoxicity at the concentrations tested in normal mammalian cell (Vero). This extract was subjected to bioassay-guided fractionation using analytical C18RP-high-performance liquid chromatography (HPLC) and an antifungal assay using P. brasiliensis. Analysis of the active fractions by HPLC-high resolution mass spectrometry allowed us to identify the antifungal agents present in the A. felis extracts cytochalasins. These results reveal the potential of A. felis as a producer of bioactive compounds with antifungal activity. PMID:27008375

  2. Novel micelle formulations to increase cutaneous bioavailability of azole antifungals.

    Science.gov (United States)

    Bachhav, Y G; Mondon, K; Kalia, Y N; Gurny, R; Möller, M

    2011-07-30

    Efficient topical drug administration for the treatment of superficial fungal infections would deliver the therapeutic agent to the target compartment and reduce the risk of systemic side effects. However, the physicochemical properties of the commonly used azole antifungals make their formulation a considerable challenge. The objective of the present investigation was to develop aqueous micelle solutions of clotrimazole (CLZ), econazole nitrate (ECZ) and fluconazole (FLZ) using novel amphiphilic methoxy-poly(ethylene glycol)-hexyl substituted polylactide (MPEG-hexPLA) block copolymers. The CLZ, ECZ and FLZ formulations were characterized with respect to drug loading and micelle size. The optimal drug formulation was selected for skin transport studies that were performed using full thickness porcine and human skin. Penetration pathways and micellar distribution in the skin were visualized using fluorescein loaded micelles and confocal laser scanning microscopy. The hydrodynamic diameters of the azole loaded micelles were between 70 and 165nm and the corresponding number weighted diameters (d(n)) were 30 to 40nm. Somewhat surprisingly, the lowest loading efficiency (13-fold higher than that from Pevaryl® cream (22.8±3.8 and 1.7±0.6μg/cm(2), respectively). A significant enhancement was also observed with human skin; the amounts of ECZ deposited were 11.3±1.6 and 1.5±0.4μg/cm(2), respectively (i.e., a 7.5-fold improvement in delivery). Confocal laser scanning microscopy images supported the hypothesis that the higher delivery observed in porcine skin was due to a larger contribution of the follicular penetration pathway. In conclusion, the significant increase in ECZ skin deposition achieved using the MPEG-dihexPLA micelles demonstrates their ability to improve cutaneous drug bioavailability; this may translate into improved clinical efficacy in vivo. Moreover, these micelle systems may also enable targeting of the hair follicle and this will be investigated

  3. Identification of Antifungal Substances of Lactobacillus sakei subsp. ALI033 and Antifungal Activity against Penicillium brevicompactum Strain FI02.

    Science.gov (United States)

    Huh, Chang Ki; Hwang, Tae Yean

    2016-03-01

    This study was performed to investigate the antifungal substances and the antifungal activity against fungi of lactic acid bacteria (LAB) isolated from kimchi. LAB from kimchi in Imsil showed antifungal activity against Penicillium brevicompactum strain FI02. LAB LI031 was identified as Lactobacillus sakei subsp. Antifungal substances contained in L. sakei subsp. ALI033 culture media were unstable at high pH levels. Both, the control and proteinase K and protease treated samples showed clear zones, suggesting that the antifungal substances produced by ALI033 were non-protein substances unaffected by protesases. Both, the control and catalase showed clear zones, suggesting that the antifungal metabolite was not H2O2. The molecular weights of the antifungal substances were ≤3,000 Da. The organic acid content of crude antifungal substances produced by L. sakei subsp. ALI033 showed high concentrations of lactic acid (502.47 mg/100 g). Therefore, these results suggest that antifungal substance produced by L. sakei subsp. ALI033 is most likely due to its ability in producing organic acid. PMID:27069906

  4. Isothermal microcalorimetry: a novel method for real-time determination of antifungal susceptibility of Aspergillus species.

    NARCIS (Netherlands)

    Furustrand Tafin, U.; Clauss, M.; Hauser, P.M.; Bille, J.; Meis, J.F.G.M.; Trampuz, A.

    2012-01-01

    We evaluated microcalorimetry for real-time susceptibility testing of Aspergillus spp. based on growth-related heat production. The minimal heat inhibitory concentration (MHIC) for A. fumigatus ATCC 204305 was 1 mg/L for amphotericin B, 0.25 mg/L for voriconazole, 0.06 mg/L for posaconazole, 0.125 m

  5. Interaction of gelatin with polyenes modulates antifungal activity and biocompatibility of electrospun fiber mats

    Directory of Open Access Journals (Sweden)

    Lakshminarayanan R

    2014-05-01

    Full Text Available Rajamani Lakshminarayanan,1,2 Radhakrishnan Sridhar,3,4 Xian Jun Loh,5 Muruganantham Nandhakumar,1 Veluchamy Amutha Barathi,1,6 Madhaiyan Kalaipriya,3,4 Jia Lin Kwan,1 Shou Ping Liu,1,2 Roger Wilmer Beuerman,1,2 Seeram Ramakrishna3,4,7 1Singapore Eye Research Institute, 2Signature Research Program in Neuroscience and Behavioral Disorders, Duke-NUS Graduate Medical School, 3Department of Mechanical Engineering, National University of Singapore, 4Center for Nanofibers and Nanotechnology, National University of Singapore, 5Institute of Materials Research and Engineering, A*STAR (Agency for Science, Technology and Research, 3 Research Link, Singapore, 6Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, 7NUS Nanoscience and Nanotechnology Initiative, Singapore Abstract: Topical application of antifungals does not have predictable or well-controlled release characteristics and requires reapplication to achieve therapeutic local concentration in a reasonable time period. In this article, the efficacy of five different US Food and Drug Administration-approved antifungal-loaded (amphotericin B, natamycin, terbinafine, fluconazole, and itraconazole electrospun gelatin fiber mats were compared. Morphological studies show that incorporation of polyenes resulted in a two-fold increase in fiber diameter and the mats inhibit the growth of yeasts and filamentous fungal pathogens. Terbinafine-loaded mats were effective against three filamentous fungal species. Among the two azole antifungals compared, the itraconazole-loaded mat was potent against Aspergillus strains. However, activity loss was observed for fluconazole-loaded mats against all of the test organisms. The polyene-loaded mats displayed rapid candidacidal activities as well. Biophysical and rheological measurements indicate strong interactions between polyene antifungals and gelatin matrix. As a result, the polyenes stabilized the triple helical

  6. Antifungal Effect of Streptomyces 702 Antifungal Monomer Component DZP8 on Rhizoctonia solani and Magnaporthe grisea

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    The aim of this study was to investigate the in vitro antifungal effects of antifungal monomer component DZP8 isolated from Streptomyces 702 on the mycelium growth, sclerotium formation and germination of Rhizoctonia solani and on the mycelium growth, conidial formation, germination, appressorium formation of Magnaporthe grisea. The results showed that the antifungal monomer component DZP8 has strong antifungal effect on both the R. solani and M. grisea. The EC50 and EC90 of DZP8 were 1.81 and 3.35 μg/ml on Ft. solani respectively, and 37.01 and 136.21 μg/ml on M. grisea respectively. Under the treatment of 48.01 μg/ml DZP8, the sclerotium formation rate of R. solani was just 39.21%, the formation time delayed by 216 h and the dry weight decreased by 81.37% in comparison the con- trol; and 33.51 μg/ml DZP8 significantly inhibited the sclerotium germination. In the presence of 160.08 μg/ml DZP8, the sporulation of M. grisea was just 9.29% of control sample; 20.14 μg/ml DZP8 inhibited the conidial germination suppression rate by 95.16%, and the appressorium formation by 100%.

  7. Topical anti-inflammatory properties of flutrimazole, a new imidazole antifungal agent.

    Science.gov (United States)

    Merlos, M; Vericat, M L; García-Rafanell, J; Forn, J

    1996-01-01

    The topical anti-inflammatory properties of flutrimazole, a new imidazole antifungal, have been evaluated. Flutrimazole inhibited mouse ear oedema induced by arachidonic acid, tetradecanoylphorbol-acetate and dithranol, with IC50 values of 3.32, 0.55 and 2.42 mumols/ear, respectively. Ketoconazole showed similar potency in arachidonic acid and dithranol models (IC50 = 3.76 and 2.41 mumols/ear) whereas it was less active against tetradecanoylphorbol acetate (IC50 = 1.96 mumols/ear). The standard anti-inflammatory sodium diclofenac was overall slightly more potent than antifungals (IC50 = 2.23, 0.57 and 0.57 mumols/ear against arachidonic acid, tetradecanoylphorbol acetate and dithranol, respectively). Both 2% flutrimazole and 2% ketoconazole creams, applied topically, inhibited carrageenan-induced rat paw oedema by about 40%. Under the same conditions, 1% flutrimazole and diclofenac creams inhibited by 26 and 54%, respectively. Flutrimazole may work through the inhibition of 5-lipoxygenase, as it inhibited LTB4 production by human granulocytes with an IC50 value of 11 microM (IC50 value for ketoconazole was 17 microM), whereas ram seminal vesicle cyclooxygenase was only inhibited by 16% at a concentration of 25 microM. Drugs such as flutrimazole, with dual anti-inflammatory/antifungal activity, may be advantageous in the treatment of topical fungal infections with an inflammatory component.

  8. Antifungal Activity of Amphotericin B Conjugated to Nanosized Magnetite in the Treatment of Paracoccidioidomycosis

    Science.gov (United States)

    Saldanha, Camila Arruda; Garcia, Mônica Pereira; Iocca, Diego Cesar; Rebelo, Luciana Guilherme; Souza, Ana Camila Oliveira; Bocca, Anamélia Lorenzetti; Almeida Santos, Maria de Fátima Menezes; Morais, Paulo Cesar; Azevedo, Ricardo Bentes

    2016-01-01

    This study reports on in vitro and in vivo tests that sought to assess the antifungal activity of a newly developed magnetic carrier system comprising amphotericin B loaded onto the surface of pre-coated (with a double-layer of lauric acid) magnetite nanoparticles. The in vitro tests compared two drugs; i.e., this newly developed form and free amphotericin B. We found that this nanocomplex exhibited antifungal activity without cytotoxicity to human urinary cells and with low cytotoxicity to peritoneal macrophages. We also evaluated the efficacy of the nanocomplex in experimental paracoccidioidomycosis. BALB/c mice were intratracheally infected with Paracoccidioides brasiliensis and treated with the compound for 30 or 60 days beginning the day after infection. The newly developed amphotericin B coupled with magnetic nanoparticles was effective against experimental paracoccidioidomycosis, and it did not induce clinical, biochemical or histopathological alterations. The nanocomplex also did not induce genotoxic effects in bone marrow cells. Therefore, it is reasonable to believe that amphotericin B coupled to magnetic nanoparticles and stabilized with bilayer lauric acid is a promising nanotool for the treatment of the experimental paracoccidioidomycosis because it exhibited antifungal activity that was similar to that of free amphotericin B, did not induce adverse effects in therapeutic doses and allowed for a reduction in the number of applications. PMID:27303789

  9. Antifungal Activity of Amphotericin B Conjugated to Nanosized Magnetite in the Treatment of Paracoccidioidomycosis.

    Science.gov (United States)

    Saldanha, Camila Arruda; Garcia, Mônica Pereira; Iocca, Diego Cesar; Rebelo, Luciana Guilherme; Souza, Ana Camila Oliveira; Bocca, Anamélia Lorenzetti; Almeida Santos, Maria de Fátima Menezes; Morais, Paulo Cesar; Azevedo, Ricardo Bentes

    2016-06-01

    This study reports on in vitro and in vivo tests that sought to assess the antifungal activity of a newly developed magnetic carrier system comprising amphotericin B loaded onto the surface of pre-coated (with a double-layer of lauric acid) magnetite nanoparticles. The in vitro tests compared two drugs; i.e., this newly developed form and free amphotericin B. We found that this nanocomplex exhibited antifungal activity without cytotoxicity to human urinary cells and with low cytotoxicity to peritoneal macrophages. We also evaluated the efficacy of the nanocomplex in experimental paracoccidioidomycosis. BALB/c mice were intratracheally infected with Paracoccidioides brasiliensis and treated with the compound for 30 or 60 days beginning the day after infection. The newly developed amphotericin B coupled with magnetic nanoparticles was effective against experimental paracoccidioidomycosis, and it did not induce clinical, biochemical or histopathological alterations. The nanocomplex also did not induce genotoxic effects in bone marrow cells. Therefore, it is reasonable to believe that amphotericin B coupled to magnetic nanoparticles and stabilized with bilayer lauric acid is a promising nanotool for the treatment of the experimental paracoccidioidomycosis because it exhibited antifungal activity that was similar to that of free amphotericin B, did not induce adverse effects in therapeutic doses and allowed for a reduction in the number of applications. PMID:27303789

  10. Antifungal Activity of Amphotericin B Conjugated to Nanosized Magnetite in the Treatment of Paracoccidioidomycosis.

    Directory of Open Access Journals (Sweden)

    Camila Arruda Saldanha

    2016-06-01

    Full Text Available This study reports on in vitro and in vivo tests that sought to assess the antifungal activity of a newly developed magnetic carrier system comprising amphotericin B loaded onto the surface of pre-coated (with a double-layer of lauric acid magnetite nanoparticles. The in vitro tests compared two drugs; i.e., this newly developed form and free amphotericin B. We found that this nanocomplex exhibited antifungal activity without cytotoxicity to human urinary cells and with low cytotoxicity to peritoneal macrophages. We also evaluated the efficacy of the nanocomplex in experimental paracoccidioidomycosis. BALB/c mice were intratracheally infected with Paracoccidioides brasiliensis and treated with the compound for 30 or 60 days beginning the day after infection. The newly developed amphotericin B coupled with magnetic nanoparticles was effective against experimental paracoccidioidomycosis, and it did not induce clinical, biochemical or histopathological alterations. The nanocomplex also did not induce genotoxic effects in bone marrow cells. Therefore, it is reasonable to believe that amphotericin B coupled to magnetic nanoparticles and stabilized with bilayer lauric acid is a promising nanotool for the treatment of the experimental paracoccidioidomycosis because it exhibited antifungal activity that was similar to that of free amphotericin B, did not induce adverse effects in therapeutic doses and allowed for a reduction in the number of applications.

  11. Antibacterial and antifungal potential of some polar solvent extracts of Ashwagandha (Solanaceae against the nosocomial pathogens

    Directory of Open Access Journals (Sweden)

    Premlata Singariya

    2012-01-01

    Full Text Available The aim of the present study is to evaluate the antimicrobial (antibacterial and antifungal effects of hexane, toluene, isopropyl alcohol, acetone and ethanolic extracts of different parts (root and stem of Withania somnifera (RUBL-20668 in order to use it as a possible source for new antimicrobial substances against important human pathogens. The dried and powdered parts were successively extracted using Soxhlet assembly; then antibacterial and antifungal activities were investigated by both, disc diffusion and serial dilution methods. The extract of W. somnifera significantly inhibited some important bacteria (two Gram +ve and four Gram-ve bacteria: Staphylococcus aureus (Gram +ve, Bacillus subtilis (Gram +ve, Escherichia coli (Gram-ve, Raoultella planticola (Gram -ve, Pseudomonas aeruginosa (Gram-ve, Enterobactor aerogens (Gram-ve, one yeast Candida albicans and one fungi Aspergillus flavus, to varying degrees. Isopropyl alcohol, acetone and toluene extracts of W. somnifera showed highest activity against the pathogens. The inhibitory effect is very identical in magnitude and comparable with that of standard antibiotics. Gentamycin, the standard antibacterial drug used, was effective in inhibiting these bacteria. The effect on E. coli, R. planticola and S. aureus were comparable to that of gentamycin. Ketoconazole, the standard antifungal used, was effective against the fungi. The inhibitory effect is very identical in magnitude and comparable with that of standard antibiotics used.

  12. Comparison of susceptibility and transcription profile of the new antifungal hassallidin A with caspofungin

    International Nuclear Information System (INIS)

    This is First report on the antifungal effects of the new glycolipopeptide hassallidin A. Due to related molecular structure moieties between hassallidin A and the established antifungal drug caspofungin we assumed parallels in the effects on cell viability. Therefore we compared hassallidin A with caspofungin by antifungal susceptibility testing and by analysing the genome-wide transcriptional profile of Candida albicans. Furthermore, we examined modifications in ultracellular structure due to hassallidin A treatment by electron microscopy. Hassallidin A was found to be fungicidal against all tested Candida species and Cryptococcus neoformans isolates. MICs ranged from 4 to 8 μg/ml, independently from the species. Electron microscopy revealed noticeable ultrastructural changes in C. albicans cells exposed to hassallidin A. Comparing the transcriptional profile of C. albicans cells treated with hassallidin A to that of cells exposed to caspofungin, only 20 genes were found to be similarly up- or down-regulated in both assays, while 227 genes were up- or down-regulated induced by hassallidin A specifically. Genes up-regulated in cells exposed to hassallidin A included metabolic and mitotic genes, while genes involved in DNA repair, vesicle docking, and membrane fusion were down-regulated. In summary, our data suggest that, although hassallidin A and caspofungin have similar structures, however, the effects on susceptibility and transcriptional response to yeasts seem to be different

  13. Concepts and principles of photodynamic therapy as an alternative antifungal discovery platform

    Directory of Open Access Journals (Sweden)

    George eTegos

    2012-04-01

    Full Text Available Opportunistic fungal pathogens may cause superficial or serious invasive infections, especially in immunocompromised and debilitated patients. Invasive mycoses represent an exponentially growing threat for human health due to a combination of slow diagnosis and the existence of relatively few classes of available and effective antifungal drugs. Therefore systemic fungal infections result in high attributable mortality. There is an urgent need to pursue and deploy novel and effective alternative anti-fungal countermeasures. Photodynamic therapy was established as a successful modality for malignancies and age-related macular degeneration but photodynamic inactivation has only recently been intensively investigated as an alternative antimicrobial discovery and development platform. The concept of photodynamic inactivation requires microbial exposure to either exogenous or endogenous photosensitizer molecules, followed by visible light energy, typically wavelengths in the red/near infrared region that cause the excitation of the photosensitizers resulting in the production of singlet oxygen and other reactive oxygen species that react with intracellular components, and consequently produce cell inactivation and death. Anti-fungal photodynamic therapy is an area of increasing interest, as research is advancing i to identify the photochemical and photophysical mechanisms involved in photoinactivation; ii to develop potent and clinically compatible photosensitizers; iii to understand how photoinactivation is affected by key microbial phenotypic elements multidrug resistance and efflux, virulence and pathogenesis determinants, and formation of biofilms; iv to explore novel photosensitizer delivery platforms and v to identify photoinactivation applications beyond the clinical setting such as environmental disinfectants.

  14. Antifungal activity of traditional medicinal plants from Tamil Nadu, India

    Institute of Scientific and Technical Information of China (English)

    Duraipandiyan V; Ignacimuthu S

    2011-01-01

    Objective:To assess the antifungal activity of hexane, ethyl acetate and methanol extracts of 45 medicinal plants and to determine the minimum inhibitory concentration for each extract against human pathogenic fungi. Methods:A total of 45 medicinal plants were collected from different places of Tamil Nadu and identified. Hexane, ethyl acetate and methanol extracts of 45 medicinal plants were assessed for antifungal susceptibility using broth microdilution method. Two known antifungal agents were used as positive controls. Results: Most of the extracts inhibited more than four fungal strains. From the evaluation we found that ethyl acetate extracts inhibited large number of fungal growth. Hexane extracts also nearly showed the same level of inhibition against fungal growth. Methanol extracts showed the minimum antifungal activity. Among the 45 plants tested, broad spectrum antifungal activity was detected in Albizzia procera (A. procera), Atalantia monophylla, Asclepias curassavica, Azima tetracantha, Cassia fistula (C. fistula), Cinnomomum verum, Costus speciosus (C. speciosus), Nymphaea stellata, Osbeckia chinensis, Piper argyrophyllum, Punica granatum, Tinospora cordifolia and Toddalia asiatica (T. asiatica). Promising antifungal activity was seen in A. procera, C. speciosus, C. fistula and T. asiatica. Conclusions:It can be concluded that the plant species assayed possess antifungal properties. Further phytochemical research is needed to identify the active principles responsible for the antifungal effects of some of these medicinal plants.

  15. Antifungal cyclic peptides from the marine sponge Microscleroderma herdmani

    Science.gov (United States)

    Screening natural product extracts from National Cancer Institute Open Repository for antifungal discovery afforded hits for bioassay-guided fractionation. Upon LC-MS analysis of column fractions with antifungal activities to generate information on chemical structure, two new cyclic hexapeptides, m...

  16. Chemical modification of antifungal polyene macrolide antibiotics

    Energy Technology Data Exchange (ETDEWEB)

    Solovieva, S E; Olsufyeva, E N; Preobrazhenskaya, M N [G.F.Gause Institute of New Antibiotics, Russian Academy of Medical Sciences (Russian Federation)

    2011-02-28

    The review summarizes advances in the methods for the synthesis of polyene antibiotics (amphotericin B, partricin A, etc.) and investigations of the structure-activity relationship made in the last 15 years. State-of-the-art approaches based on the combination of the chemical synthesis and genetic engineering are considered. Emphasis is given to the design of semisynthetic antifungal agents against chemotherapy-resistant pathogens having the highest therapeutic indices. Recent results of research on the mechanisms of action of polyenes are outlined.

  17. Synthesis of Novel Antifungal Triazole Compounds

    Institute of Scientific and Technical Information of China (English)

    Yong CHU; Ming Xia XU; Ding LU

    2004-01-01

    Based on our previous studies of 3D-QSAR, 38 novel objective compounds belonging to 4 series were designed and successfully synthesized directed by the idea of reconstructing the structure of non-pharmacophores while reserving essential ones in triazoles. In vitro pilot studies on their antifungal activities showed that most compounds have inhibitory effects on C.albicans and some inhibit S.cerevisiae also. The effects on C.albicans of 5 compounds are more potent than or equal to that of fluconazole or itraconazole.

  18. Chemical modification of antifungal polyene macrolide antibiotics

    International Nuclear Information System (INIS)

    The review summarizes advances in the methods for the synthesis of polyene antibiotics (amphotericin B, partricin A, etc.) and investigations of the structure-activity relationship made in the last 15 years. State-of-the-art approaches based on the combination of the chemical synthesis and genetic engineering are considered. Emphasis is given to the design of semisynthetic antifungal agents against chemotherapy-resistant pathogens having the highest therapeutic indices. Recent results of research on the mechanisms of action of polyenes are outlined.

  19. Isolation of antifungally active lactobacilli from edam cheese

    DEFF Research Database (Denmark)

    Tuma, S.; Vogensen, Finn Kvist; Plocková, M.;

    2007-01-01

    The antifungal activity of 322 lactobacilli strains isolated from Edam cheese at different stages of the ripening process was tested against Fusarium proliferatum M 5689 using a dual overlay spot assay. Approximately 21% of the isolates showed a certain level of inhibitory activity. Seven strains...... with the strongest antifungal activity were examined by the milk agar plate method with three different mould strains isolated from spoiled dairy products as target microorganisms and were compared with the antifungal effectiveness of standard antifungal strains Lactobacillus rhamnosus VT1 and Lb. plantarum DC 1246...... as Lb. paracasei and three as Lb. fermentum. Lb. paracasei ST 68 was chosen for further testing as antifungal protective adjunct for Edam cheese production.  ...

  20. Advances in synthetic approach to and antifungal activity of triazoles

    Directory of Open Access Journals (Sweden)

    Pramod Kumar Sharma

    2011-05-01

    Full Text Available Several five membered ring systems, e.g., triazole, oxadiazole dithiazole and thiadiazole with three heteroatoms at symmetrical or asymmetrical positions have been studied because of their interesting pharmacological properties. In this article our emphasis is on synthetic development and pharmacological activity of the triazole moiety which exhibit a broad spectrum of pharmacological activity such as antifungal, antibacterial, anti-inflammatory and anticancer etc. Triazoles have increased our ability to treat many fungal infections, for example, candidiasis, cryptococcal meningitis, aspergillosis etc. However, mortality due to these infections even with antifungal therapy is still unacceptably high. Therefore, the development of new antifungal agents targeting specific fungal structures or functions is being actively pursued. Rapid developments in molecular mycology have led to a concentrated search for more target antifungals. Although we are entering a new era of antifungal therapy in which we will continue to be challenged by systemic fungal diseases, the options for treatment will have greatly expanded.

  1. CHARACTERIZATION AND ANTIFUNGAL SUSCEPTIBILITY PATTERN OF CANDIDA SPP . ISOLATED FROM CLINICAL SPECIMENS

    Directory of Open Access Journals (Sweden)

    Sagarika

    2015-05-01

    Full Text Available BACKGROUND: With the changing health scenario fungal infections have increased significantly, contributing to morbidity, mortality and health care cost. Candida is major human fungal pathogens that cause both superficial and deep tissue infections. With emergence of non - albicans Candida species, availability of advanced identification methods and antifungal resistance, the spectrum of candidiasis has changed. OBJ ECTIVE: The aim of our study was to identify the distribution of Candida species among clinical isolates, risk factors associated with candidiasis and their sensitivity pattern for common antifungal drugs. MATERIALS AND METHODS: One hundred thirty nine dif ferent clinical isolates of Candida were collected from indoor patients of a tertiary care centre of Gujarat from May 2009 to June 2010. Identification of Candida species and antifungal susceptibility testing was performed with miniAPI (Analytical Prophylactic Index (Biomerieux, France which is an automatic identification and susceptibility testing instrument. RESULTS: We found that the non ‑ albicans Candida were more prevalent than Candida albicans . Candida tropicalis (48.9% was the most common Candida spp. and also more resistant than that of C.albicans . C.albicans showed resistance against fluconazole (3.5% and itraconazole (8.8% whereas C.tropicalis were res istant to amphotericin B (10.3%, fluconazole (20.7%, itraconazole (32.3%, and voriconazole (23.5% and flucytosine (5.8%. Overall resistance rates of Candida for amphotericin B, fluconazole, itraconazole, and voriconazole and flucytosine were 6.4%, 15. 2%, 22.3%, 12.9%, 5% respectively. CONCLUSION: To achieve better clinical results species ‑ level identification of Candida spp. and their antifungal sensitivity testing should be performed.

  2. New aminoporphyrins bearing urea derivative substituents: synthesis, characterization, antibacterial and antifungal activity

    Directory of Open Access Journals (Sweden)

    Gholamreza Karimipour

    2015-06-01

    Full Text Available This work studied the synthesis of 5,10,15-tris(4-aminophenyl-20-(N,N-dialkyl/diaryl-N-phenylurea porphyrins (P1-P4 with alkyl or aryl groups of Ph, iPr, Et and Me, respectively and also the preparation of their manganese (III and cobalt (II complexes (MnP and CoP. The P1-P4 ligands were characterized by different spectroscopic techniques (1H NMR, FTIR, UV-Vis and elemental analysis, and metalated with Mn and Co acetate salts. The antibacterial and antifungal activities of these compounds in vitro were investigated by agar-disc diffusion method against Escherichia coli (-, Pseudomonas aeruginosa (-, Staphylococcus aureus(+, Bacillus subtilis (+ and Aspergillus oryzae and Candida albicans. Results showed that antibacterial and antifungal activity of the test samples increased with increase of their concentrations and the highest activity was obtained when the concentration of porphyrin compounds was 100 µg/mL. The activity for the porphyrin ligands depended on the nature of the urea derivative substituents and increased in the order P1 > P2 > P3 >P4, which was consistent with the order of their liposolubility. MnP and CoP complexes exhibited much higher antibacterial and antifungal activity than P1-P4ligands. Further, the growth inhibitory effects of these compounds was generally in the order CoP complexes > MnP complexes > P1-P4 ligands. Among these porphyrin compounds, CoP1displayed the highest antibacterial and antifungal activity, especially with a concentration of 100 µg/mL, against all the four tested bacteria and two fungi, and therefore it could be potential to be used as drug.

  3. Drug: D02557 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 026 Antifungal agents Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] D DERMATOLOGICALS D01 ANTIFUNGAL...S FOR DERMATOLOGICAL USE D01A ANTIFUNGALS FOR TOPICAL USE D01AC Imida

  4. Drug: D02923 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available s map07026 Antifungal agents Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] D DERMATOLOGICALS D01 ANTIFUNGAL...S FOR DERMATOLOGICAL USE D01A ANTIFUNGALS FOR TOPICAL USE D01A

  5. Drug: D00883 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available agents Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] D DERMATOLOGICALS D01 ANTIFUNGAL...S FOR DERMATOLOGICAL USE D01A ANTIFUNGALS FOR TOPICAL USE D01AE Other antifungals f

  6. The Antifungal Eugenol Perturbs Dual Aromatic and Branched-Chain Amino Acid Permeases in the Cytoplasmic Membrane of Yeast

    OpenAIRE

    Emad Darvishi; Mansoor Omidi; Ali Akbar Shahnejat Bushehri; Ashkan Golshani; Smith, Myron L.

    2013-01-01

    Eugenol is an aromatic component of clove oil that has therapeutic potential as an antifungal drug, although its mode of action and precise cellular target(s) remain ambiguous. To address this knowledge gap, a chemical-genetic profile analysis of eugenol was done using ∼4700 haploid Saccharomyces cerevisiae gene deletion mutants to reveal 21 deletion mutants with the greatest degree of susceptibility. Cellular roles of deleted genes in the most susceptible mutants indicate that the main targe...

  7. Novel antifungal peptides from Ceylon spinach seeds.

    Science.gov (United States)

    Wang, H; Ng, T B

    2001-11-01

    Two novel antifungal peptides, designated alpha- and beta-basrubrins, respectively, were isolated from seeds of the Ceylon spinach Basella rubra. The purification procedure involved saline extraction, (NH(4))(2)SO(4) precipitation, ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on CM-cellulose and FPLC-gel filtration on Superdex peptide column. alpha- and beta-basrubrins exhibited a molecular weight of 4.3 and 5 kDa, respectively. They inhibited translation in a rabbit reticulocyte system with an IC(50) value of 400 and 100 nM, respectively. alpha- and beta-basrubrin inhibited HIV-1 reverse transcriptase by (79.4 +/- 7.8)% and (54.6 +/- 3.6)%, respectively, at a concentration of 400 microM, and (10.56 +/- 0.92)% and (2.12 +/- 0.81)%, respectively, at a concentration of 40 microM. Both alpha- and beta-basrubrins exerted potent antifungal activity toward Botrytis cinerea, Mycosphaerella arachidicola, and Fusarium oxysporum. PMID:11688973

  8. In vitro and In vivo Evaluation of Select Kahalalide F Analogs with Antitumor and Antifungal Activities

    OpenAIRE

    Shilabin, Abbas Gholipour; Hamann, Mark T

    2011-01-01

    Kahalalide F (KF) and the regioisomer isoKF are novel anticancer drugs of marine origin and currently under clinical investigation. Here we report the synthesis of two new KF analogs with significant in vitro and in vivo antifungal and antitumor activities. The primary amine hydrogen of ornithine in KF has been replaced with 4-fluoro-3-methylbenzyl and morpholin-4-yl-benzyl via reductive N-alkylation. The TGI of these analogs using the NCI-60 cell line screening revealed promising results whe...

  9. Antifungal Activity of Brazilian Propolis Microparticles against Yeasts Isolated from Vulvovaginal Candidiasis

    Directory of Open Access Journals (Sweden)

    Kelen Fátima Dalben Dota

    2011-01-01

    Full Text Available Propolis, a resinous compound produced by Apis mellifera L. bees, is known to possess a variety of biological activities and is applied in the therapy of various infectious diseases. The aim of this study was to evaluate the in vitro antifungal activity of propolis ethanol extract (PE and propolis microparticles (PMs obtained from a sample of Brazilian propolis against clinical yeast isolates of importance in the vulvovaginal candidiasis (VVC. PE was used to prepare the microparticles. Yeast isolates (n=89, obtained from vaginal exudates of patients with VVC, were exposed to the PE and the PMs. Moreover, the main antifungal drugs used in the treatment of VVC (Fluconazole, Voriconazole, Itraconazole, Ketoconazole, Miconazole and Amphotericin B were also tested. Minimum inhibitory concentration (MIC was determined according to the standard broth microdilution method. Some Candida albicans isolates showed resistance or dose-dependent susceptibility for the azolic drugs and Amphotericin B. Non-C. albicans isolates showed more resistance and dose-dependent susceptibility for the azolic drugs than C. albicans. However, all of them were sensitive or dose-dependent susceptible for Amphotericin B. All yeasts were inhibited by PE and PMs, with small variation, independent of the species of yeast. The overall results provided important information for the potential application of PMs in the therapy of VVC and the possible prevention of the occurrence of new symptomatic episodes.

  10. Synergism of Antifungal Activity between Mitochondrial Respiration Inhibitors and Kojic Acid

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    Ronald P. Haff

    2013-01-01

    Full Text Available Co-application of certain types of compounds to conventional antimicrobial drugs can enhance the efficacy of the drugs through a process termed chemosensitization. We show that kojic acid (KA, a natural pyrone, is a potent chemosensitizing agent of complex III inhibitors disrupting the mitochondrial respiratory chain in fungi. Addition of KA greatly lowered the minimum inhibitory concentrations of complex III inhibitors tested against certain filamentous fungi. Efficacy of KA synergism in decreasing order was pyraclostrobin > kresoxim-methyl > antimycin A. KA was also found to be a chemosensitizer of cells to hydrogen peroxide (H2O2, tested as a mimic of reactive oxygen species involved in host defense during infection, against several human fungal pathogens and Penicillium strains infecting crops. In comparison, KA-mediated chemosensitization to complex III inhibitors/H2O2 was undetectable in other types of fungi, including Aspergillus flavus, A. parasiticus, and P. griseofulvum, among others. Of note, KA was found to function as an antioxidant, but not as an antifungal chemosensitizer in yeasts. In summary, KA could serve as an antifungal chemosensitizer to complex III inhibitors or H2O2 against selected human pathogens or Penicillium species. KA-mediated chemosensitization to H2O2 seemed specific for filamentous fungi. Thus, results indicate strain- and/or drug-specificity exist during KA chemosensitization.

  11. Serious drug interactions.

    Science.gov (United States)

    Aronson, J

    1993-10-01

    Of the many varieties of drug interactions, which occur when the disposition or actions of one drug are changed by another, only a few are serious or potentially fatal. A representative outline of some of these illustrates the problem. Precipitant drugs are those which produce the interaction, and object drugs are those whose effects are changed. The interactions which are usually significant are those which alter the metabolism, involve renal excretion, or change the effects of the object drug, especially when the object drug has a low therapeutic index (cardiovascular drugs, anticoagulants, drugs acting on the brain, hypoglycemic drugs, hormones, and cytotoxic drugs). Warfarin toxicity, for example, is produced by aspirin, phenylbutazone, and azapropazone. The dosage requirements of warfarin are reduced by chloramphenicol, ciprofloxacin and other quinolones, erythromycin and some of the other macrolides, metronidazole and other imidazoles, tetracyclines, amiodarone, cimetidine (but not ranitidine), and fibrates. Potassium-depleting drugs can potentiate the action of digoxin, and the elimination of digoxin can be reduced by amiodarone, propafenone, quinidine, and verapamil. Combined oral contraceptives can lose effectiveness through the interaction of carbamazepine, griseofulvin, phenytoin, or rifampicin, which increase estrogen metabolism. In addition, broad-spectrum antibiotics such as ampicillin or tetracyclines also reduce contraceptive effectiveness by altering gut absorption. Even a single drink of an alcoholic beverage may be dangerous to people taking antidepressants, antihistamines, antipsychotic drugs, benzodiazepines, or lithium. Antihistamines suffer inhibited metabolism in the liver if taken in conjunction with the antifungal imidazoles and some of the macrolide antibiotics. Cardiotoxicity of antihistamines is also enhanced by drugs with similar cardiotoxic effects. Lithium potentiation is enhanced by the new serotonin-reuptake inhibitors, and lithium

  12. Antifungal Activity of Copaifera langsdorffii Desf Oleoresin against Dermatophytes

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    Nádia R. B. Raposo

    2013-10-01

    Full Text Available Dermatophytoses are mycoses that affect keratinized tissues in both humans and animals. The aim of this study was to investigate the antifungal activity of the oleoresin extracted from Copaifera langsdorffii Desf. against the strains Microsporum canis ATCC 32903, Microsporum gypseum ATCC 14683, Trichophyton mentagrophytes ATCC 11481 and Trichophyton rubrum CCT 5507. The antimicrobial activity was determined by minimum inhibitory concentration (MIC and minimum fungicidal concentration (MFC values. Ketoconazole and terbinafine were used as reference drugs. The copaiba oleoresin showed moderate fungicidal activity against T. mentagrophytes ATCC 11481 (MIC and MFC = 170 μg mL−1 and weak fungicidal activity against T. rubrum CCT 5507 (MIC = 1,360 μg mL−1 and MFC = 2,720 μg mL−1. There was no activity against M. canis ATCC 32903 and M. gypseum ATCC 14683. SEM analysis revealed physical damage and morphological alterations such as compression and hyphae clustering in the structure of the fungi exposed to the action of the oleoresin. The results stimulate the achievement of in vivo assays to confirm the benefits of the application of oleoresin extracted from copaiba in the treatment of dermatophytosis, both in humans and in animals.

  13. Metabolomics and Cheminformatics Analysis of Antifungal Function of Plant Metabolites

    Directory of Open Access Journals (Sweden)

    Miroslava Cuperlovic-Culf

    2016-09-01

    Full Text Available Fusarium head blight (FHB, primarily caused by Fusarium graminearum, is a devastating disease of wheat. Partial resistance to FHB of several wheat cultivars includes specific metabolic responses to inoculation. Previously published studies have determined major metabolic changes induced by pathogens in resistant and susceptible plants. Functionality of the majority of these metabolites in resistance remains unknown. In this work we have made a compilation of all metabolites determined as selectively accumulated following FHB inoculation in resistant plants. Characteristics, as well as possible functions and targets of these metabolites, are investigated using cheminformatics approaches with focus on the likelihood of these metabolites acting as drug-like molecules against fungal pathogens. Results of computational analyses of binding properties of several representative metabolites to homology models of fungal proteins are presented. Theoretical analysis highlights the possibility for strong inhibitory activity of several metabolites against some major proteins in Fusarium graminearum, such as carbonic anhydrases and cytochrome P450s. Activity of several of these compounds has been experimentally confirmed in fungal growth inhibition assays. Analysis of anti-fungal properties of plant metabolites can lead to the development of more resistant wheat varieties while showing novel application of cheminformatics approaches in the analysis of plant/pathogen interactions.

  14. Susceptibility pattern of Malassezia species to selected plant extracts and antifungal agents

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    G Sibi

    2014-01-01

    Full Text Available Objective: Malassezia is associated with dandruff, seborrhoeic dermatitis, pityriasis versicolor folliculitis and atopic eczema. This study determined the susceptibility pattern of Malassezia furfur, M. globosa, M. obtusa, M. restricta, M. slooffiae and M. sympodialis isolated from patients diagnosed with dandruff against plant extracts and antifungal agents. Materials and Methods: Twenty aqueous plant extracts and five azole drugs were tested against the isolates by well diffusion and broth dilution method. Results: Among the plant extracts, Phyllanthus emblica (fruits, Hibiscus rosa sinensis (flowers and Acacia concinna (pods have demonstrated significant antidandruff activity. Minimum inhibitory concentration values revealed that ketoconazole as the most effective drug followed by itraconazole. Conclusion: M. furfur and M. globosa were found as the most susceptible organisms against the aqueous extracts of Phyllanthus emblica (fruits, Hibiscus rosa sinensis (flowers, Acacia concinna (pods and azole drugs.

  15. Antifungal activities of Terminalia ivorensis A. Chev. bark extracts against Candida albicans and Aspergillus fumigatus.

    OpenAIRE

    Ouattara Sitapha; KPOROU KOUASSI ELISEE; Djaman Allico Joseph

    2013-01-01

    Abstract The present study was undertaken to evaluate in vitro antifungal activity of aqueous and hydroacoholic extracts from bark of Terminalia ivorensis A. Chev. (Combretaceae). In vitro antifungal activity of all the extracts was done by agar slant double dilution method. Candida albicans and Aspergillus fumigatus clinically important strains were used for the study. ketoconazole was used as standards for antifungal assay. Antifungal activity was determinated by evaluating of antifung...

  16. Antifungal Activity of Fruit Extracts of Different Water Chestnut Varieties

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    Mohammad ANOWAR RAZVY

    2011-03-01

    Full Text Available The antifungal activity of three varieties (red, green and wild of water chestnut fruit extracts was studied against a number of fungal species. A strong antifungal activity of ethanol and petroleum extract was found against the treated fungi resulting remarkable inhibition zone in comparison to both Dithane-M45 fungicide and control. It has also been evident that wild variety of water chestnut was comparatively more efficient in respect to antifungal activity compared to the red and green variety of the same plant.

  17. Functionalised isocoumarins as antifungal compounds: Synthesis and biological studies.

    Science.gov (United States)

    Simic, Milena; Paunovic, Nikola; Boric, Ivan; Randjelovic, Jelena; Vojnovic, Sandra; Nikodinovic-Runic, Jasmina; Pekmezovic, Marina; Savic, Vladimir

    2016-01-01

    A series of novel 3-substituted isocoumarins was prepared via Pd-catalysed coupling processes and screened in vitro for antifungal activity against Candida species. The study revealed antifungal potential of isocoumarins possessing the azole substituents, which, in some cases, showed biological properties equal to those of clinically used voriconazole. Selected compounds were also screened against voriconazole resistant Candida krusei 6258 and a clinical isolate Candida parapsilosis CA-27. Although the activity against these targets needs to be improved further, the results emphasise additional potential of this new class of antifungal compounds. PMID:26586600

  18. Antifungal activities of ethanolic extract from Jatropha curcas seed cake.

    Science.gov (United States)

    Saetae, Dolaporn; Suntornsuk, Worapot

    2010-02-01

    Phorbol ester extraction was carried out from Jatropha curcas seed cake, a by-product from the bio-diesel fuel industry. Four repeated extractions from 5 g J. curcas seed cake using 15 ml of 90% (v/v) ethanol and a shaking speed of 150 rev/min gave the highest yield of phosbol esters. The ethanolic extract of J. curcas seed cake showed antifungal activities against important phytofungal pathogens: Fusarium oxysporum, Pythium aphanidermatum, Lasiodiplodia theobromae, Curvularia lunata, Fusarium semitectum, Colletotrichum capsici and Colletotrichum gloeosporiodes. The extract contained phorbol esters mainly responsible for antifungal activities. The extract could therefore be used as an antifungal agent for agricultural applications. PMID:20208435

  19. Oral Candidiasis among Cancer Patients Attending a Tertiary Care Hospital in Chennai, South India: An Evaluation of Clinicomycological Association and Antifungal Susceptibility Pattern.

    Science.gov (United States)

    Jayachandran, Abirami Lakshmy; Katragadda, Radhika; Thyagarajan, Ravinder; Vajravelu, Leela; Manikesi, Suganthi; Kaliappan, Shanmugam; Jayachandran, Balaji

    2016-01-01

    Oropharyngeal candidiasis is one of the common manifestations seen in cancer patients on cytotoxic therapy and invasion into deeper tissues can occur if not treated promptly. Emergence of antifungal drug resistance is of serious concern owing to the associated morbidity and mortality. The present study aims at evaluation of clinicomycological association and antifungal drug susceptibility among the 180 recruited patients with cancer on chemotherapy and/or radiotherapy with signs or symptoms suggestive of oral candidiasis. Speciation and antifungal susceptibility was done by Microbroth dilution method for fluconazole, Itraconazole, and Amphotericin B as per standard microbiological techniques. Chi-square test was used for statistical analysis (p < 0.05 was considered statistically significant). Candida albicans was the predominant species isolated (94) (58%) followed by Candida tropicalis (34) (20.9%). Fluconazole and Itraconazole showed an overall resistance rate of 14% and 14.8%, respectively. All the isolates were susceptible to Amphotericin B. There was a significant association between the presence of dry mouth and isolation of Candida (p < 0.001). Such clinicomicrobiological associations can help in associating certain symptoms with the isolation of Candida. Species level identification with in vitro antifungal susceptibility pattern is essential to choose the appropriate drug and to predict the outcome of therapy.

  20. Design, Synthesis, Antifungal Activities and 3D-QSAR of New N,N'-Diacylhydrazines Containing 2,4-Dichlorophenoxy Moiety

    Directory of Open Access Journals (Sweden)

    Bao-Ju Li

    2013-11-01

    Full Text Available A series of new N,N'-diacylhydrazine derivatives were designed and synthesized. Their structures were verified by 1H-NMR, mass spectra (MS and elemental analysis. The antifungal activities of these N,N'-diacylhydrazines were evaluated. The bioassay results showed that most of these N,N'-diacylhydrazines showed excellent antifungal activities against Cladosporium cucumerinum, Corynespora cassiicola, Sclerotinia sclerotiorum, Erysiphe cichoracearum, and Colletotrichum orbiculare in vivo. The half maximal effective concentration (EC50 of one of the compounds was also determined, and found to be comparable with a commercial drug. To further investigate the structure–activity relationship, comparative molecular field analysis (CoMFA was performed on the basis of antifungal activity data. Both the steric and electronic field distributions of CoMFA are in good agreement in this study.

  1. Design, synthesis, antifungal activities and 3D-QSAR of new N,N'-diacylhydrazines containing 2,4-dichlorophenoxy moiety.

    Science.gov (United States)

    Sun, Na-Bo; Shi, Yan-Xia; Liu, Xing-Hai; Ma, Yi; Tan, Cheng-Xia; Weng, Jian-Quan; Jin, Jian-Zhong; Li, Bao-Ju

    2013-01-01

    A series of new N,N'-diacylhydrazine derivatives were designed and synthesized. Their structures were verified by 1H-NMR, mass spectra (MS) and elemental analysis. The antifungal activities of these N,N'-diacylhydrazines were evaluated. The bioassay results showed that most of these N,N'-diacylhydrazines showed excellent antifungal activities against Cladosporium cucumerinum, Corynespora cassiicola, Sclerotinia sclerotiorum, Erysiphe cichoracearum, and Colletotrichum orbiculare in vivo. The half maximal effective concentration (EC50) of one of the compounds was also determined, and found to be comparable with a commercial drug. To further investigate the structure-activity relationship, comparative molecular field analysis (CoMFA) was performed on the basis of antifungal activity data. Both the steric and electronic field distributions of CoMFA are in good agreement in this study. PMID:24189221

  2. Design, Synthesis, Antifungal Activities and 3D-QSAR of New N,N′-Diacylhydrazines Containing 2,4-Dichlorophenoxy Moiety

    Science.gov (United States)

    Sun, Na-Bo; Shi, Yan-Xia; Liu, Xing-Hai; Ma, Yi; Tan, Cheng-Xia; Weng, Jian-Quan; Jin, Jian-Zhong; Li, Bao-Ju

    2013-01-01

    A series of new N,N′-diacylhydrazine derivatives were designed and synthesized. Their structures were verified by 1H-NMR, mass spectra (MS) and elemental analysis. The antifungal activities of these N,N′-diacylhydrazines were evaluated. The bioassay results showed that most of these N,N′-diacylhydrazines showed excellent antifungal activities against Cladosporium cucumerinum, Corynespora cassiicola, Sclerotinia sclerotiorum, Erysiphe cichoracearum, and Colletotrichum orbiculare in vivo. The half maximal effective concentration (EC50) of one of the compounds was also determined, and found to be comparable with a commercial drug. To further investigate the structure–activity relationship, comparative molecular field analysis (CoMFA) was performed on the basis of antifungal activity data. Both the steric and electronic field distributions of CoMFA are in good agreement in this study. PMID:24189221

  3. ANTIFUNGAL ACTIVITY OF CORALLOCARPUS EPIGAEUS (HOOK. F.

    Directory of Open Access Journals (Sweden)

    Vasantha K

    2012-01-01

    Full Text Available In the present study, petroleum ether, hexane, chloroform, acetone and methanol extracts of leaf, stem and tuber of C. epigaeus were investigated for antifungal activity against Candida albicans, C. tropicalis, Aspergillus niger, A. flavus and A. versicolor by disc diffusion method. Methanol extract of C. epigaeus tuber exhibited maximum activity against most of the tested fungi. The petroleum ether and hexane extracts obtained from C. epigaeus stem was found to be active only against A. niger, A. flavus and A. versicolor. All the crude extracts exhibited activity against A. niger and A. flavus. The tuber extract of C. epigaeus showed higher inhibitory effect than leaf and stem. This kind of study could generate more such ideas for re-inventing and using herbs in combination to treat many more diseases.

  4. Antifungal steroid saponins from Dioscorea cayenensis.

    Science.gov (United States)

    Sautour, M; Mitaine-Offer, A-C; Miyamoto, T; Dongmo, A; Lacaille-Dubois, M-A

    2004-01-01

    From the rhizomes of Dioscorea cayenensis Lam.-Holl (Dioscoreaceae), the new 26- O- beta- D-glucopyranosyl-22-methoxy-3 beta,26-dihydroxy-25( R)-furost-5-en-3- O- alpha- L-rhamnopyranosyl-(1-->4)- alpha- L-rhamnopyranosyl-(1-->4)-[ alpha- L-rhamnopyranosyl-(1-->2)]- beta- D-glucopyranoside ( 1) was isolated together with the known dioscin ( 2) and diosgenin 3- O- alpha- L-rhamnopyranosyl-(1-->4)- alpha- L-rhamnopyranosyl-(1-->4)-[ alpha- L-rhamnopyranosyl-(1-->2)]- beta- D-glucopyranoside ( 3). Their structures were established on the basis of spectral data. Compound 2 exhibited antifungal activity against the human pathogenic yeasts Candida albicans, C. glabrata and C. tropicalis (MICs of 12.5, 12.5 and 25 micro g/mL, respectively) whereas 3 showed weak activity and 1 was inactive. PMID:14765305

  5. Naturally occurring antifungal aromatic esters and amides

    International Nuclear Information System (INIS)

    During the search of antifungal natural products from terrestrial plants, a new long chained aromatic ester named grandiflorate along with spatazoate from Portulaca grandiflora and N-[2-methoxy-2-(4-methoxyphenyl) ethyl]-trans-cinnamide and aegeline from Solanum erianthum of Nigeria were isolated and tested against six fungal species. The known constituents have not been reported so far from mentioned investigated plants. Structures of the isolated compounds were elucidated with the aid of spectroscopic techniques including two dimensional NMR experiments. Among the compounds, the esters found more potent than amides against Candida albicans and Aspergillus flavus. The new compound grandiflorate gave response against all tested fungal species while aegeline was found to give lowest inhibition during this study. (author)

  6. Anti-fungal activity of irradiated chitosan

    International Nuclear Information System (INIS)

    Anti-fungal activity of chitosan induced by irradiation has been investigated. Commercial chitosan samples of 8B (80% deacetylation) and l0B (99% deacetylation) were irradiated by γ-ray in dry condition. Highly deacethylated chitosan (10B) at low dose irradiation (75 kGy) was effective for inhibition of fungal growth. The sensitivities of Exobasidium vexans, Septoria chrysanthemum and Gibberella fujikuroi for the irradiated chitosan were different and the necessary concentrations of chitosan were 550, 350 and 250 μg/ml, respectively. For the plant growth, low deacethylation (chitosan 8B) and high dose (500 kGy) was effective and the growth of chrysanthemum was promoted by spraying the irradiated chitosan. (author)

  7. Antifungal susceptibility and distribution of Candida spp. isolates from the University Hospital in the municipality of Dourados, State of Mato Grosso do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    Adriana Araujo de Almeida

    2013-06-01

    Full Text Available Introduction Hospital infections caused by Candida spp. are a leading cause of morbidity and mortality in hospitalized patients, particularly those that are critically ill or immunocompromised. In this study, the distribution of Candida species in isolates from the University Hospital of the Federal University at Grande Dourados and their in vitro susceptibility to antifungal drugs were analyzed. Methods Yeasts were phenotypically identified using classical methodologies. Antifungal susceptibility tests to amphotericin B and fluconazole were performed using the broth microdilution technique. Results A total of 50 Candida isolates were obtained from hospitalized patients during the study period. We analyzed yeast isolates from urine (n=31; 62%, blood (n=12; 24%, and tracheal secretions (n=7; 14%. The following Candida species were identified: C. tropicalis (n=21; 42%, C. albicans (n=18; 36%, C. glabrata (n=10; 20%, and C. krusei (n=1; 2%. Antifungal susceptibility tests demonstrated that C. albicans was susceptible to both antifungal agents. However, 31.2% of the non-C. albicans Candida isolates displayed dose-dependent susceptibility to fluconazole, and 3.1% were resistant to amphotericin B. Conclusions In contrast to previous reports, our results indicated that C. tropicalis was the most commonly isolated yeast species among the hospital patients. The predominance of non-C. albicans Candida infections confirms the importance of species-level identification for implementing appropriate antifungal therapies.

  8. Research to Identify Effective Antifungal Agents, 1993 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Schreck, Carl

    1993-10-01

    This study is a continuation of ``Research to Identify Effective Antifungal Agents'' sponsored by Bonneville Power Administration (Schreck et al. 1990, 1991, and 1992). The objectives of the present study were to select and evaluate candidate fungicides.

  9. Antifungal Effect of (+-Pinoresinol Isolated from Sambucus williamsii

    Directory of Open Access Journals (Sweden)

    Bomi Hwang

    2010-05-01

    Full Text Available In this study, we investigated the antifungal activity and mechanism of action of (+-pinoresinol, a biphenolic compound isolated from the herb Sambucus williamsii,used in traditional medicine. (+-Pinoresinol displays potent antifungal properties without hemolytic effects on human erythrocytes. To understand the antifungal mechanism of (+-pinoresinol, we conducted fluorescence experiments on the human pathogen Candida albicans. Fluorescence analysis using 1,6-diphenyl-1,3,5-hexatriene (DPH indicated that the (+-pinoresinol caused damage to the fungal plasma membrane. This result was confirmed by using rhodamine-labeled giant unilamellar vesicle (GUV experiments. Therefore, the present study indicates that (+-pinoresinol possesses fungicidal activities and therapeutic potential as an antifungal agent for the treatment of fungal infectious diseases in humans.

  10. Antifungal effect of (+)-pinoresinol isolated from Sambucus williamsii.

    Science.gov (United States)

    Hwang, Bomi; Lee, Juneyoung; Liu, Qing-He; Woo, Eun-Rhan; Lee, Dong Gun

    2010-05-14

    In this study, we investigated the antifungal activity and mechanism of action of (+)-pinoresinol, a biphenolic compound isolated from the herb Sambucus williamsii,used in traditional medicine. (+)-Pinoresinol displays potent antifungal properties without hemolytic effects on human erythrocytes. To understand the antifungal mechanism of (+)-pinoresinol, we conducted fluorescence experiments on the human pathogen Candida albicans. Fluorescence analysis using 1,6-diphenyl-1,3,5-hexatriene (DPH) indicated that the (+)-pinoresinol caused damage to the fungal plasma membrane. This result was confirmed by using rhodamine-labeled giant unilamellar vesicle (GUV) experiments. Therefore, the present study indicates that (+)-pinoresinol possesses fungicidal activities and therapeutic potential as an antifungal agent for the treatment of fungal infectious diseases in humans.

  11. Synthesis and Antifungal Activity of Musa Phytoalexins and Structural Analogs

    OpenAIRE

    Adriana Gallego; Gloria Cardona; Victor Arango; Yoni Rosero; Fernando Torres; Fernando Echeverri; Gustavo Escobar; Winston Quiñones

    2000-01-01

    Several perinaphthenone/phenylphenalenone compounds were synthesized to establish a relationship between structure and antifungal activity against Mycosphaerella fijiensis. Substitutions on the unsaturated carbonyl system or addition of a phenyl group reduced antibiotic activity.

  12. Solubility, photostability and antifungal activity of phenylpropanoids encapsulated in cyclodextrins.

    Science.gov (United States)

    Kfoury, Miriana; Lounès-Hadj Sahraoui, Anissa; Bourdon, Natacha; Laruelle, Frédéric; Fontaine, Joël; Auezova, Lizette; Greige-Gerges, Hélène; Fourmentin, Sophie

    2016-04-01

    Effects of the encapsulation in cyclodextrins (CDs) on the solubility, photostability and antifungal activities of some phenylpropanoids (PPs) were investigated. Solubility experiments were carried out to evaluate the effect of CDs on PPs aqueous solubility. Loading capacities and encapsulation efficiencies of freeze-dried inclusion complexes were determined. Moreover, photostability assays for both inclusion complexes in solution and solid state were performed. Finally, two of the most widespread phytopathogenic fungi, Fusarium oxysporum and Botrytis cinerea, were chosen to examine the antifungal activity of free and encapsulated PPs. Results showed that encapsulation in CDs significantly increased the solubility and photostability of studied PPs (by 2 to 17-fold and 2 to 44-fold, respectively). Free PPs revealed remarkable antifungal properties with isoeugenol showing the lowest half-maximal inhibitory concentration (IC50) values of mycelium growth and spore germination inhibition. Encapsulated PPs, despite their reduced antifungal activity, could be helpful to solve drawbacks such as solubility and stability.

  13. Research to Identify Effective Antifungal Agents, 1991 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Schreck, Carl

    1991-09-01

    This study is a continuation of ``Research to Identify Effective Antifungal Agents'' sponsored by Bonneville Power Administration (Schreck et al. 1990). The objectives of the present study was to evaluate up to 10 candidate fungicides.

  14. Antifungal activity of fruit pulp extract from Bromelia pinguin.

    Science.gov (United States)

    Camacho-Hernández, I L; Chávez-Velázquez, J A; Uribe-Beltrán, M J; Ríos-Morgan, A; Delgado-Vargas, F

    2002-08-01

    The methanol extract of the fruit pulp of Bromelia pinguin was evaluated for its antifungal activity. The extract showed a significant activity against some Trichophyton strains, although Candida strains were generally insensitive.

  15. Synthesis and Antifungal Activity of Musa Phytoalexins and Structural Analogs

    Directory of Open Access Journals (Sweden)

    Adriana Gallego

    2000-07-01

    Full Text Available Several perinaphthenone/phenylphenalenone compounds were synthesized to establish a relationship between structure and antifungal activity against Mycosphaerella fijiensis. Substitutions on the unsaturated carbonyl system or addition of a phenyl group reduced antibiotic activity.

  16. Cryptic antifungal compounds active by synergism with polyene antibiotics.

    Science.gov (United States)

    Kinoshita, Hiroshi; Yoshioka, Mariko; Ihara, Fumio; Nihira, Takuya

    2016-04-01

    The majority of antifungal compounds reported so far target the cell wall or cell membrane of fungi, suggesting that other types of antibiotics cannot exert their activity because they cannot penetrate into the cells. Therefore, if the permeability of the cell membrane could be enhanced, many antibiotics might be found to have antifungal activity. We here used the polyene antibiotic nystatin, which binds to ergosterol and forms pores at the cell membrane, to enhance the cellular permeability. In the presence of nystatin, many culture extracts from entomopathogenic fungi displayed antifungal activity. Among all the active extracts, two active components were purified and identified as helvolic acid and terramide A. Because the minimum inhibitory concentration of either compound was reduced four-fold in the presence of nystatin, it can be concluded that this screening method is useful for detecting novel antifungal activity.

  17. Antifungal activity of Bacillus sp. isolated from compost.

    Science.gov (United States)

    Czaczyk, K; Stachowiak, B; Trojanowska, K; Gulewicz, K

    2000-01-01

    Four strains of Bacillus isolated from lupine compost exhibited an antifungal activity against six plant fungal pathogens (Rhizoctonia solani, Bipolaris sorokiniana, Sclerotinia sclerotiorum, Trichothecium roseum, Fusarium solani, Fusarium oxysporum). It was significantly influenced by the composition of the cultivation media.

  18. Inhibition of Rat and Human Steroidogenesis by Triazole Antifungals

    Science.gov (United States)

    Environmental chemicals that alter steroid production could interfere with male reproductive development and function. Three agricultural antifungal triazoles (myclobutanil, propiconazole and triadimefon) that are known to modulate expression of cytochrome P450 (CYP) genes and e...

  19. Screening for antifungal activities of extracts of the brazilian seaweed genus Laurencia (Ceramiales, Rhodophyta

    Directory of Open Access Journals (Sweden)

    Erika M. Stein

    2011-04-01

    Full Text Available The resistance of pathogens to commonly used antibiotics has enhanced morbidity and mortality and has triggered the search for new drugs. Several species of the red alga genus Laurencia are very interesting candidates as potential sources of natural products with pharmaceutical activity because they are known to produce a wide range of chemically interesting halogenated secondary metabolites. This is an initial report of the antifungal activities of the secondary metabolites of five species of Laurencia, collected in the state of Espírito Santo, against three strains of pathogenic fungi: Candida albicans (CA, Candida parapsilosis (CP, and Cryptococcus neoformans (CN. Minimum inhibitory concentrations (MIC of the algal extracts were determined by serial dilution method in RPMI 1640 Medium in 96-well plates according to the NCCLS and microbial growth was determined by absorbance at 492nm. A result showing maintenance or reduction of the inoculum was defined as fungistatic, while fungicidal action was no observed growth in the 10 µL fungistatic samples subcultured in Sabouraud Agar. Our results indicate that apolar extracts of Laurencia species possess antifungal properties and encourage continued research to find new drugs for therapy of infectious diseases in these algae.

  20. Prevalence of Candida Infection and its Antifungal Susceptibility Pattern in Tertiary Care Hospital, Ahmedabad

    Directory of Open Access Journals (Sweden)

    Lata R Patel

    2012-08-01

    Full Text Available Introduction: In the past three decades with the use of potent antibacterial immunosuppressive and cytotoxic drugs, lethal invasive candidiasis has been described with increasing frequency. Patients admitted at tertiary care hospitals have access to very intensive management modalities. This, along with increasing number of immune-compromised patients, has lead to rise in infections caused by candida especially by NCA (Non Candida Albicans. Methodology: Duration of the study was from 1st July- 2011 to 30th June 2012. Candida species isolated from various clinical specimens were subjected to speciation using standard yeast identification protocol and CHROM agar. Antifungal susceptibility testing was done by the disc diffusion method against Amphotericin B and Azole group of antifungals like Fluconazole, Itraconazole, Clotrimazole and Voriconazole. Results: Among the 430 culture positive isolates 161(37.4% were C. albicans and 269 (62.6% were non candida albicans. Among NCA, 176(40.9% were C. tropicalis followed by other species. Susceptibility pattern showed that Azole group 25.5% sensitive among C. albicans and 18.7% sensitive among C. tropicalis while in Amphotericin B sensitivity varies from 75.6% to 100% to all isolated spp. of candida. Conclusion: In this study C. tropicalis was the most common yeast isolated from all the clinical samples. The C. albicans and NCA showed highly susceptible to Amphotericin B, followed by Voriconazole & Clotrimazole, is the drug of choice. [Natl J of Med Res 2012; 2(4.000: 439-441

  1. SCREENING OF ANTIFUNGAL EFFECTS OF PSEUDOCLITOCYBE CYATHIFORMIS Bull. (Singer)

    OpenAIRE

    Perihan Güler; Fatih Kutluer; Taşkın Erol; Erkan Eren; İlknur Kunduz; Hayriye Biçer

    2013-01-01

    In this study, antifungal activities of Pseudoclitocybe cyathiformis extracts with the help of acetone and chloroform against to Fusarium species (Fusarium culmorum and Fusarium moniliforme) were investigated. Pseudoclitocybe cyathiformis was dried at aseptic conditions and put thru extractions for 12 hours in solvents. Than the evaporator at 40°C and finally dried material stored at + 4°C.(Jonathan and Fasidi, 2003). Antifungal activities were measured by Disc Diffusion method (Stoke and Rid...

  2. Design, Synthesis and Evaluation of Macrocyclic Antifungal Peptides

    OpenAIRE

    Mulder, M.P.C.

    2012-01-01

    Fungi are increasingly recognised as major additional pathogens in already critically ill patients. Invasive fungal infections represent a growing threat and over the past two decades the incidence and diversity of fungal infections has increased enormously, especially among immunocompromised patients and patients hospitalized with serious underlying diseases. Resistance against and toxicity of the current antifungal agents underscores the urgent need for development of new antifungal compoun...

  3. Screening of Iranian plants for antifungal activity: Part 1

    Directory of Open Access Journals (Sweden)

    Amin Gh.R

    2002-07-01

    Full Text Available In this study, 250 species from 37 families of native Iranian plants were screened for in vitro antifungal activity against 19 fungal strains in vitro. Primarily, the crude extracts at concentration of 100μg/ml were tested. Of 250 extracts tested, 185(74% showed antifungal activity against at least one fungal strain. The outstanding species were Artemisia aucheri, Artemisia scoparia, Carthamus oxyacantha, Francoeuria undulate, Tripleurospermum disciform, and Xanthium spinosum.

  4. Potent heterologous antifungal proteins from cheeseweed (Malva parviflora).

    Science.gov (United States)

    Wang, X; Bunkers, G J

    2000-12-20

    Two novel antifungal proteins were purified and characterized from cheeseweed (Malva parviflora). Both proteins, designated CW-1 and CW-2, are composed of two different subunits of 5000 and 3000 Da, respectively. These proteins possess very potent antifungal activities, and more interestingly the inhibition is fungicidal instead of fungistatic. At low salt condition, the IC(50) of CW-1 and CW-2 against Fusarium graminearum (Fg) is 2.5 ppm. At high salt condition which diminishes the antifungal activity of many antifungal proteins, both CW-1 and CW-2 still maintain potent activity against Fg with IC(50) of 10 ppm. The two subunits could be separated by gel filtration in the presence of 6 M urea, but their antifungal activity cannot be recovered after the removal of urea. Amino acid sequence analysis indicates that both subunits of CW-1 show homology to 2S albumin, whereas the two subunits of CW-2 have homology to vicilin protein from cotton. To our knowledge, this is the first report of isolation and characterization of heterologous antifungal proteins from any source.

  5. An antifungal peptide from Phaseolus vulgaris cv. brown kidney bean

    Institute of Scientific and Technical Information of China (English)

    Yau Sang Chan; Jack Ho Wong; Evandro Fei Fang; Wen Liang Pan; Tzi Bun Ng

    2012-01-01

    A 5.4-kDa antifungal peptide,with an N-terminal sequence highly homologous to defensins and inhibitory activity against Mycosphaerella arachidicola (IC5o=3 μM),Setospaeria turcica and Bipolaris maydis,was isolated from the seeds of Phaseolus vulgaris cv.brown kidney bean.The peptide was purified by employing a protocol that entailed adsorption on Affi-gel blue gel and Mono S and finally gel filtration on Superdex 75.The antifungal activity of the peptide against M.arachidicola was stable in the pH range 3-12 and in the temperature range 0℃ to 80℃.There was a slight reduction of the antifungal activity at pH 2 and 13,and the activity was indiscernible at pH 0,1,and 14.The activity at 90℃ and 100℃ was slightly diminished.Deposition of Congo red at the hyphal tips of M.arachidicola was induced by the peptide indicating inhibition of hyphal growth.The lack of antiproliferative activity of brown kidney bean antifungal peptide toward tumor cells,in contrast to the presence of such activity of other antifungal peptides,indicates that different domains are responsible for the antifungal and antiproliferative activities.

  6. 3-Bromopyruvate: a novel antifungal agent against the human pathogen Cryptococcus neoformans.

    Science.gov (United States)

    Dyląg, Mariusz; Lis, Paweł; Niedźwiecka, Katarzyna; Ko, Young H; Pedersen, Peter L; Goffeau, Andre; Ułaszewski, Stanisław

    2013-05-01

    We have investigated the antifungal activity of the pyruvic acid analogue: 3-bromopyruvate (3-BP). Growth inhibition by 3-BP of 110 strains of yeast-like and filamentous fungi was tested by standard spot tests or microdilution method. The human pathogen Cryptococcus neoformans exhibited a low Minimal Inhibitory Concentration (MIC) of 0.12-0.15 mM 3-BP. The high toxicity of 3-BP toward C. neoformans correlated with high intracellular accumulation of 3-BP and also with low levels of intracellular ATP and glutathione. Weak cytotoxicity towards mammalian cells and lack of resistance conferred by the PDR (Pleiotropic Drug Resistance) network in the yeast Saccharomyces cerevisiae, are other properties of 3-BP that makes it a novel promising anticryptococcal drug. PMID:23541578

  7. Antifungal Hydroxy Fatty Acids Produced during Sourdough Fermentation: Microbial and Enzymatic Pathways, and Antifungal Activity in Bread

    OpenAIRE

    Black, Brenna A.; Zannini, Emanuele; Curtis, Jonathan M.; Gänzle, Michael G

    2013-01-01

    Lactobacilli convert linoleic acid to hydroxy fatty acids; however, this conversion has not been demonstrated in food fermentations and it remains unknown whether hydroxy fatty acids produced by lactobacilli have antifungal activity. This study aimed to determine whether lactobacilli convert linoleic acid to metabolites with antifungal activity and to assess whether this conversion can be employed to delay fungal growth on bread. Aqueous and organic extracts from seven strains of lactobacilli...

  8. Candidiasis drug discovery and development: new approaches targeting virulence for discovering and identifying new drugs

    Science.gov (United States)

    Pierce, Christopher G.; Lopez-Ribot, Jose L.

    2014-01-01

    Introduction Targeting pathogenetic mechanisms rather than essential processes represents a very attractive alternative for the development of new antibiotics. This may be particularly important in the case of antimycotics, due to the urgent need for novel antifungal drugs and the paucity of selective fungal targets. The opportunistic pathogenic fungus Candida albicans is the main etiological agent of candidiasis, the most common human fungal infection. These infections carry unacceptably high mortality rates, a clear reflection of the many shortcomings of current antifungal therapy, including the limited armamentarium of antifungal agents, their toxicity, and the emergence of resistance. Moreover the antifungal pipeline is mostly dry. Areas covered This review covers some of the most recent progress towards understanding C. albicans pathogenetic processes and how to harness this information for the development of anti-virulence agents. The two principal areas covered are filamentation and biofilm formation, as C. albicans pathogenicity is intimately linked to its ability to undergo morphogenetic conversions between yeast and filamentous morphologies and to its ability to form biofilms. Expert opinion We argue that filamentation and biofilm formation represent high value targets, yet clinically unexploited, for the development of novel anti-virulence approaches against candidiasis. Although this has proved a difficult task despite increasing understanding at the molecular level of C. albicans virulence, we highlight new opportunities and prospects for antifungal drug development targeting these two important biological processes. PMID:23738751

  9. 9-O-butyl-13-(4-isopropylbenzyl)berberine, KR-72, is a potent antifungal agent that inhibits the growth of Cryptococcus neoformans by regulating gene expression.

    Science.gov (United States)

    Bang, Soohyun; Kwon, Hyojeong; Hwang, Hyun Sook; Park, Ki Duk; Kim, Sung Uk; Bahn, Yong-Sun

    2014-01-01

    In this study we explored the mode of action of KR-72, a 9-O-butyl-13-(4-isopropylbenzyl)berberine derivative previously shown to exhibit potent antifungal activity against a variety of human fungal pathogens. The DNA microarray data revealed that KR-72 treatment significantly changed the transcription profiles of C. neoformans, affecting the expression of more than 2,000 genes. Genes involved in translation and transcription were mostly upregulated, whereas those involved in the cytoskeleton, intracellular trafficking, and lipid metabolism were downregulated. KR-72 also exhibited a strong synergistic effect with the antifungal agent FK506. KR-72 treatment regulated the expression of several essential genes, including ECM16, NOP14, HSP10 and MGE1, which are required for C. neoformans growth. The KR-72-mediated induction of MGE1 also likely reduced the viability of C. neoformans by impairing cell cycle or the DNA repair system. In conclusion, KR-72 showed antifungal activity by modulating diverse biological processes through a mode of action distinct from those of clinically available antifungal drugs such as polyene and azole drugs.

  10. Species Distribution and In Vitro Antifungal Susceptibility of Vulvovaginal Candida Isolates in China

    Institute of Scientific and Technical Information of China (English)

    Feng-Juan Wang; Dai Zhang; Zhao-Hui Liu; Wen-Xiang Wu; Hui-Hui Bai; Han-Yu Dong

    2016-01-01

    Background:Vulvovaginal candidiasis (VVC) was a common infection associated with lifelong harassment of woman's social and sexual life.The purpose of this study was to describe the species distribution and in vitro antifungal susceptibility of Candida species (Candida spp.) isolated from patients with WC over 8 years.Methods:Species which isolated from patients with WC in Peking University First Hospital were identified using chromogenic culture media.Susceptibility to common antifungal agents was determined using agar diffusion method based on CLSI M44-A2 document.SPSS software (version 14.0,Inc.,Chicago,IL,USA) was used for statistical analysis,involving statistical description and Chi-square test.Results:The most common strains were Candida (C.) albicans,80.5% (n =1775) followed by C.glabrata,18.1% (n =400).Nystatin exhibited excellent activity against all species (<4% resistant [R]).Resistance to azole drugs varied among different species.C albicans:clotrimazole (3.1% R) < fluconazole (16.6% R) < itraconazole (51.5% R) < miconazole (54.0% R);C.glabrata:miconazole (25.6% R) < clotrimazole (50.5% R) < itraconazole (61.9% R) < fluconazole (73.3% R);Candida krusei:clotrimazole (0 R) < fluconazole (57.7% R) < miconazole (73.1% R) < itraconazole (83.3% R).The susceptibility offluconazole was noticeably decreasing among all species in the study period.Conclusions:Nystatin was the optimal choice for the treatment of WC at present.The species distribution and in vitro antifungal susceptibility of Candida spp.isolated from patients with VVC had changed over time.

  11. Antifungal and molluscicidal saponins from Serjania salzmanniana.

    Science.gov (United States)

    Ekabo, O A; Farnsworth, N R; Henderson, T O; Mao, G; Mukherjee, R

    1996-04-01

    An investigation of Serjania salzmanniana for biologically active substances has led to the isolation of two novel saponins, salzmannianoside A (3-O-[[beta-D- glucopyranosyl-(1-->4)]-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L- arabinopyranosyl] gypsogenin) [3] and salzmannianoside B (3-O-[[beta-D-glucopyranosyl-(1-->4)]-[alpha-L- arabinopyranosyl-(1-->3)-alpha-L-rhamnopyranosyl-(1-->2)] -alpha-L-arabinopyranosyl] hederagenin) (4). Two known saponins, pulsatilla saponin D (3-O-[[beta-D- glucopyranosyl-(1-->4)]-[alpha-L-rhamnopyranosyl-(1-->2)]-alpha-L- arabinopyranosyl] hederagenin) (1) and 3-O-[[beta-D-glucopyranosyl-(1-->4)]-[alpha-L-rhamnopyranosyl-(1-->2)]-a lpha-L- arabinopyranosyl] oleanolic acid (2) were also isolated from this plant. The structures of 3 and 4 were elucidated by FABMS and 2D NMR techniques. All these four saponins were mollusicidal, causing 70-100% mortality at 10 ppm against Biomphalaria alexandrina, a vector of Schistosoma mansoni in the Nile Valley. The saponins also showed antifungal activity against Cryptococcus neoformans and Candida albicans at minimal inhibitory concentrations of 8 and 16 micrograms/mL, respectively.

  12. Antifungal hydroxy fatty acids produced during sourdough fermentation: microbial and enzymatic pathways, and antifungal activity in bread.

    Science.gov (United States)

    Black, Brenna A; Zannini, Emanuele; Curtis, Jonathan M; Gänzle, Michael G

    2013-03-01

    Lactobacilli convert linoleic acid to hydroxy fatty acids; however, this conversion has not been demonstrated in food fermentations and it remains unknown whether hydroxy fatty acids produced by lactobacilli have antifungal activity. This study aimed to determine whether lactobacilli convert linoleic acid to metabolites with antifungal activity and to assess whether this conversion can be employed to delay fungal growth on bread. Aqueous and organic extracts from seven strains of lactobacilli grown in modified De Man Rogosa Sharpe medium or sourdough were assayed for antifungal activity. Lactobacillus hammesii exhibited increased antifungal activity upon the addition of linoleic acid as a substrate. Bioassay-guided fractionation attributed the antifungal activity of L. hammesii to a monohydroxy C(18:1) fatty acid. Comparison of its antifungal activity to those of other hydroxy fatty acids revealed that the monohydroxy fraction from L. hammesii and coriolic (13-hydroxy-9,11-octadecadienoic) acid were the most active, with MICs of 0.1 to 0.7 g liter(-1). Ricinoleic (12-hydroxy-9-octadecenoic) acid was active at a MIC of 2.4 g liter(-1). L. hammesii accumulated the monohydroxy C(18:1) fatty acid in sourdough to a concentration of 0.73 ± 0.03 g liter(-1) (mean ± standard deviation). Generation of hydroxy fatty acids in sourdough also occurred through enzymatic oxidation of linoleic acid to coriolic acid. The use of 20% sourdough fermented with L. hammesii or the use of 0.15% coriolic acid in bread making increased the mold-free shelf life by 2 to 3 days or from 2 to more than 6 days, respectively. In conclusion, L. hammesii converts linoleic acid in sourdough and the resulting monohydroxy octadecenoic acid exerts antifungal activity in bread.

  13. A novel assay of biofilm antifungal activity reveals that amphotericin B and caspofungin lyse Candida albicans cells in biofilms.

    Science.gov (United States)

    DiDone, Louis; Oga, Duana; Krysan, Damian J

    2011-08-01

    The ability of Candida albicans to form drug-resistant biofilms is an important factor in its contribution to human disease. Assays to identify and characterize molecules with activity against fungal biofilms are crucial for the development of drugs with improved anti-biofilm activity. Here we report the application of an adenylate kinase (AK)-based cytotoxicity assay of fungal cell lysis to the characterization of agents active against C. albicans biofilms. We have developed three protocols for the AK assay. The first measures AK activity in the supernatants of biofilms treated with antifungal drugs and can be performed in parallel with a standard 2,3-bis-(2-methoxy-4-nitro-5-sulphophenyl)-2H-tetrazolium-5-caboxanilide-based biofilm susceptibility assay; a second, more sensitive protocol measures the AK activity present within the biofilm matrix; and a third procedure allows the direct visualization of lytic activity toward biofilms formed on catheter material. Amphotericin B and caspofungin, the two most effective anti-biofilm drugs currently used to treat fungal infections, both directly lyse planktonic C. albicans cells in vitro, leading to the release of AK into the culture medium. These studies serve to validate the AK-based lysis assay as a useful addition to the methods for the characterization of antifungal agents active toward biofilms and provide insights into the mode of action of amphotericin B and caspofungin against C. albicans biofilms.

  14. A novel assay of biofilm antifungal activity reveals that amphotericin B and caspofungin lyse Candida albicans cells in biofilms.

    Science.gov (United States)

    DiDone, Louis; Oga, Duana; Krysan, Damian J

    2011-08-01

    The ability of Candida albicans to form drug-resistant biofilms is an important factor in its contribution to human disease. Assays to identify and characterize molecules with activity against fungal biofilms are crucial for the development of drugs with improved anti-biofilm activity. Here we report the application of an adenylate kinase (AK)-based cytotoxicity assay of fungal cell lysis to the characterization of agents active against C. albicans biofilms. We have developed three protocols for the AK assay. The first measures AK activity in the supernatants of biofilms treated with antifungal drugs and can be performed in parallel with a standard 2,3-bis-(2-methoxy-4-nitro-5-sulphophenyl)-2H-tetrazolium-5-caboxanilide-based biofilm susceptibility assay; a second, more sensitive protocol measures the AK activity present within the biofilm matrix; and a third procedure allows the direct visualization of lytic activity toward biofilms formed on catheter material. Amphotericin B and caspofungin, the two most effective anti-biofilm drugs currently used to treat fungal infections, both directly lyse planktonic C. albicans cells in vitro, leading to the release of AK into the culture medium. These studies serve to validate the AK-based lysis assay as a useful addition to the methods for the characterization of antifungal agents active toward biofilms and provide insights into the mode of action of amphotericin B and caspofungin against C. albicans biofilms. PMID:21674619

  15. Antimycobacterial and Antifungal Activities of Selected Four Salvia Species

    Directory of Open Access Journals (Sweden)

    Nur Tan

    2016-03-01

    Full Text Available The content of essential oils of endemic Salvia cilicica was analyzed by GC-FID and GC-MS techniques. Spathulenol (23.8 %, caryophyllene oxide (14.9 % and hexadecanoic acid (10.3 % were identified as the major components in the oil of Salvia cilicica. Additionally, in this study ethanol extracts of the aerial parts and essential oils of four Salvia species ( S. cilicica, S. officinalis, S. fruticosa, S. tomentosa , as well as the roots of S. cilicica were investigated their antimycobacterial and antifungal activities including infectious diseases. The antimycobacterial activity was analyzed against three Mycobacterium tuberculosis (sensitive-, resistant-standard strains and multidrug resistance clinical isolate strains and the antifungal activity was compared with two dermotophytes (Microsporum gypseum and Trichophyton mentagrophytes var. erinacei and three Candida species by the broth microdilution method. The essentials oils of the four tested Salvia species showed high antimycobacterial and antifungal activity (MIC between 0.2-12.5 mcg/mL in comparison to the aerial parts and root extracts . The antifungal and antimycobacterial potential of the ethanol extracts and essential oils were introduced to determine whether, Salvia species can be used in phytotherapy against the yeasts, dermatophytes and M. tuberculosis. To the best of our knowledge this is the first study of S. cilicica about their antimycobacterial and antifungal activities and chemical composition of its essential oils.

  16. Antifungal susceptibilities of Candida species isolated from urine culture.

    Science.gov (United States)

    Toka Özer, Türkan; Durmaz, Süleyman; Yula, Erkan

    2016-09-01

    Candida spp. are the most common opportunistic mycosis worldwide. Although Candida albicans is the most common cause of urinary tract infections, the frequency of non-albicans Candida species is increasing with common use of antifungal in the prophylaxis and treatment. This may lead to difficulties in treatment. Antifungal tests should be applied with identification of species for effective treatment. In this study, identification of Candida species isolated from urine culture and investigation of susceptibility of these strains to amphotericin B, flucytosine, fluconazole, voriconazole was aimed. In this study, 58 Candida strains isolated from urine cultures at Osmaniye State Hospital between January 2012 and April 2013 were included. Urine culture and antifungal susceptibility tests were applied. Incidence rate of Candida spp. was determined as C. albicans (56.9%), Candida glabrata (20.6%), Candida tropicalis (10.3%), Candida parapsilosis (7%), Candida krusei (3.4%), Candida kefyr (1.8%). Most of the isolates were susceptible to amphotericin B, flucytosine, fluconazole, voriconazole. Twenty three (39.7%) Candida strains were isolated from internal medical branches and Intensive Care Unit and 12 (20.6%) from the Surgical Medical Branches. C. albicans and C. glabrata species were isolated most frequently as a candiduria factor in this hospital between January 2012 and April 2013. The analysis of antifungal susceptibility profile shows no significant resistance to antifungals.

  17. Drug: D03315 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Antifungal ATC code: D01AE04 Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] D DERMATOLOGICALS D01 ANTIFUNGAL...S FOR DERMATOLOGICAL USE D01A ANTIFUNGALS FOR TOPICAL USE D01AE Other antifungals for to

  18. Drug: D05815 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05815 Drug Selenium sulfide (USP); Exsel (TN) SeS2 143.8607 143.09 D05815.gif Anti... antifungals for topical use D01AE13 Selenium sulfide D05815 Selenium sulfide (US...P) D11 OTHER DERMATOLOGICAL PREPARATIONS D11A OTHER DERMATOLOGICAL PREPARATIONS D11AC Medicated shampoos D11AC03 Selenium... compounds D05815 Selenium sulfide (USP) USP drug classification [BR:br08302] Dermatological Agents Selenium D05815 Sele...olytes Electrolyte/Mineral Replacement Selenium D05815 Selenium sulfide (USP) CAS: 7488-56-4 PubChem: 472074

  19. Drug: D01980 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D01980 Drug Luliconazole (JAN/USAN/INN); Lulicon (TN); Luzu (TN) C14H9Cl2N3S2 352.9615 354.2774 D01980...ing individual organs 26 Epidermides 265 Antiparasitic dermatosis agents 2655 Imidazoles D01980... Luliconazole (JAN/USAN/INN) USP drug classification [BR:br08302] Antifungals Luliconazole D01980...erol 14alpha-demethylase inhibitor [KO:K05917] Imidazoles Luliconazole D01980 Lul...iconazole (JAN/USAN/INN) CAS: 187164-19-8 PubChem: 7849042 LigandBox: D01980 NIKKAJI: J937.034J ATOM 21 1 C8

  20. Drug: D05220 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D05220 Drug Octanoic acid (USAN/INN) C8H16O2 144.115 144.2114 D05220.gif Antifungal... Same as: C06423 map07011 Penicillins CAS: 124-07-2 PubChem: 47206939 DrugBank: DB04519 PDB-CCD: OCA LigandBox: D05220...92 4 C1b C 26.2881 -17.3604 5 C6a C 21.4316 -17.3604 6 C1b C 27.4992 -18.0592 7 O6a O 20.220

  1. Saccharomyces cerevisiae biofilm tolerance towards systemic antifungals depends on growth phase

    DEFF Research Database (Denmark)

    Bojsen, Rasmus Kenneth; Regenberg, Birgitte; Folkesson, Sven Anders

    2014-01-01

    growing planktonic cells, voriconazole had limited antifungal activity, flucytosine was fungistatic, caspofungin and amphotericin B were fungicidal. In growth-arrested cells, only amphotericin B had antifungal activity. Confocal microscopy and colony count viability assays revealed that the response...

  2. Interference of Plectranthus amboinicus (Lour.) Spreng essential oil on the anti-Candida activity of some clinically used antifungals Interferência do óleo essencial de Plectranthus amboinicus (Lour.) Spreng sobre a atividade anti-Candida de alguns antifúngicos utilizados clinicamente

    OpenAIRE

    Rinalda de Araújo G. Oliveira; EDELTRUDES O. LIMA; Souza, Evandro L.; Wellington L. Vieira; Kristerson R. L. Freire; Vinícius N. Trajano; Igara O. Lima; Raimundo N. Silva-Filho

    2007-01-01

    Plants with medicinal properties have been applied for a long in the traditional health care, so that sometimes their use takes place concomitantly to the use of industrialized drugs. The aim of this study was to evaluate the interference of Plectranthus amboinicus essential oil on the anti-Candida activity of some clinically used antifungals by the solid medium diffusion procedure. Assayed antifungals were amphotericin B (100 µg/mL), ketoconazole (50 µg/mL) and itraconazole (50 &...

  3. Molecular mechanisms of action of herbal antifungal alkaloid berberine, in Candida albicans.

    Directory of Open Access Journals (Sweden)

    Sanjiveeni Dhamgaye

    Full Text Available Candida albicans causes superficial to systemic infections in immuno-compromised individuals. The concomitant use of fungistatic drugs and the lack of cidal drugs frequently result in strains that could withstand commonly used antifungals, and display multidrug resistance (MDR. In search of novel fungicidals, in this study, we have explored a plant alkaloid berberine (BER for its antifungal potential. For this, we screened an in-house transcription factor (TF mutant library of C. albicans strains towards their susceptibility to BER. Our screen of TF mutant strains identified a heat shock factor (HSF1, which has a central role in thermal adaptation, to be most responsive to BER treatment. Interestingly, HSF1 mutant was not only highly susceptible to BER but also displayed collateral susceptibility towards drugs targeting cell wall (CW and ergosterol biosynthesis. Notably, BER treatment alone could affect the CW integrity as was evident from the growth retardation of MAP kinase and calcineurin pathway null mutant strains and transmission electron microscopy. However, unlike BER, HSF1 effect on CW appeared to be independent of MAP kinase and Calcineurin pathway genes. Additionally, unlike hsf1 null strain, BER treatment of Candida cells resulted in dysfunctional mitochondria, which was evident from its slow growth in non-fermentative carbon source and poor labeling with mitochondrial membrane potential sensitive probe. This phenotype was reinforced with an enhanced ROS levels coinciding with the up-regulated oxidative stress genes in BER-treated cells. Together, our study not only describes the molecular mechanism of BER fungicidal activity but also unravels a new role of evolutionary conserved HSF1, in MDR of Candida.

  4. ArtinM offers new perspectives in the development of antifungal therapy

    Directory of Open Access Journals (Sweden)

    Luciana Pereira Ruas

    2012-06-01

    Full Text Available The thermally dimorphic fungus Paracoccidioides brasiliensis is the causative agent of paracoccidioidomycosis (PCM, the most frequent systemic mycosis that affects the rural populations in Latin America. Despite significant developments in antifungal chemotherapy, its efficacy remains limited since drug therapy is prolonged and associated with toxic side effects and relapses. In response to these challenges, it is now recognized that several aspects of antifungal immunity can be modulated to better deal with fungal infections. A common idea for halting fungal infections has been the need to activate a cell-based, pro-inflammatory Th1 immune response to improve the fungal elimination. ArtinM, a D-mannose binding lectin from Artocarpus heterophyllus, has the property of modulating immunity against several intracellular pathogens. Here, we review the immunomodulatory activity of ArtinM during experimental PCM in mice. Both prophylactic and therapeutic protocols of ArtinM administration promotes a Th1 immune response balanced by IL-10, which outstandingly reduces the fungal load in organs of the treated mice while maintaining a controlled inflammation at the site of infection. A carbohydrate recognition based interaction of ArtinM

  5. Identification and Antifungal Susceptibility of Penicillium-Like Fungi from Clinical Samples in the United States.

    Science.gov (United States)

    Guevara-Suarez, Marcela; Sutton, Deanna A; Cano-Lira, José F; García, Dania; Martin-Vicente, Adela; Wiederhold, Nathan; Guarro, Josep; Gené, Josepa

    2016-08-01

    Penicillium species are some of the most common fungi observed worldwide and have an important economic impact as well as being occasional agents of human and animal mycoses. A total of 118 isolates thought to belong to the genus Penicillium based on morphological features were obtained from the Fungus Testing Laboratory at the University of Texas Health Science Center in San Antonio (United States). The isolates were studied phenotypically using standard growth conditions. Molecular identification was made using two genetic markers, the internal transcribed spacer (ITS) and a fragment of the β-tubulin gene. In order to assess phylogenetic relationships, maximum likelihood and Bayesian inference assessments were used. Antifungal susceptibility testing was performed according to CLSI document M38-A2 for nine antifungal drugs. The isolates were identified within three genera, i.e., Penicillium, Talaromyces, and Rasamsonia The most frequent species in our study were Penicillium rubens, P. citrinum, and Talaromyces amestolkiae The potent in vitro activity of amphotericin B (AMB) and terbinafine (TRB) and of the echinocandins against Penicillium and Talaromyces species might offer a good therapeutic alternative for the treatment of infections caused by these fungi. PMID:27280422

  6. Yeasts from the oral cavity of children with AIDS: exoenzyme production and antifungal resistance

    Directory of Open Access Journals (Sweden)

    Bosco Vera Lúcia

    2003-01-01

    Full Text Available The oral fungal microbiota of 30 children with AIDS, of both genders, aged from two to six years, receiving outpatient treatment, was evaluated and compared with that of a control group composed of 30 healthy subjects with matching ages and genders. Virulence factors, such as exoenzyme production, and susceptibility to five antifungal agents using an E-Test kit were evaluated. C. albicans predominated over other species in the AIDS group, showing a higher production of proteinase and phospholipase when compared with that observed in the control group. In this study few clinical manifestations of and low selectivity for C. albicans (23.3% were observed in the AIDS group. The enzymatic studies showed that 53.8% of the AIDS strains were strongly positive whereas only 33.3% of the non-AIDS strains were positive. Amphotericin B was the most effective drug among the antifungal agents tested against C. albicans. The frequency, selectivity and level of exoenzyme production by C. albicans suggest a higher pathogenicity in the AIDS children than in the control children.

  7. Assessment of plant lectin antifungal potential against yeasts of major importance in medical mycology.

    Science.gov (United States)

    Klafke, Gabriel Baracy; Moreira, Gustavo Marçal Schmitt Garcia; Monte, Leonardo Garcia; Pereira, Juliano Lacava; Brandolt, Tchana Martinez; Xavier, Melissa Orzechowski; Santi-Gadelha, Tatiane; Dellagostin, Odir Antonio; Pinto, Luciano da Silva

    2013-02-01

    The search for new compounds with antifungal activity is accelerating due to rising yeast and fungal resistance to commonly prescribed drugs. Among the molecules being investigated, plant lectins can be highlighted. The present work shows the potential of six plant lectins which were tested in vitro against yeasts of medical importance, Candida albicans, Candida tropicalis, Candida parapsilosis, Cryptococcus gattii, Cryptococcus neoformans, Malassezia pachydermatis, Rhodotorula sp. and Trichosporon sp. Broth microdilution susceptibility testing was performed in accordance with standard protocols to evaluate antifungal activity. Minimum inhibitory concentration (MIC) was determined at 80% yeast growth inhibition, whereas the minimum fungicidal concentration (MFC) was evaluated after making the subcultures of each dilution. Only C. parapsilosis growth was inhibited by the lectins tested. Abelmoschus esculentus lectin showed the highest MIC (0.97 μg ml(-1)). Lectins from Canavalia brasiliensis, Mucuna pruriens and Clitoria fairchildiana presented the highest MFC at (3.90 μg ml(-1)). These results encourage further studies with wider yeast strain selections, and open new perspectives for the development of pharmacological molecules. PMID:23161017

  8. A cultured endophyte community is associated with the plant Clerodendrum inerme and antifungal activity.

    Science.gov (United States)

    Gong, B; Yao, X H; Zhang, Y Q; Fang, H Y; Pang, T C; Dong, Q L

    2015-01-01

    Fungal endophytes live in the inner tissues of Clerodendrum inerme and may be significant resources for new chemicals in drug discovery. A total of 242 endophytic fungi were recovered from 602 sample segments of C. inerme; 66 were purified. The 66 fungi belonging to 16 taxa and 11 genera (Alternaria, Nigrospora, Bartalinia, Pestalotiopsis, Fusarium, Mycoleptodiscus, Trichoderma, Phomopsis, Diaporthe, Lasiodiplodia, and Curvularia) were identified by morphological characteristics and fungal internal transcribed spacer sequences. The most abundant genera were Alternaria and Lasiodiplodia. Some of the endophytes exhibited tissue specificity. The colonization frequencies of endophytes in the stems were evidently higher than those in the roots and leaves. The crude ethyl acetate extracts were tested against 6 endophytes isolated from C. inerme. Three of 10 (33.3%) endophytes, which were identified as Phomopsis sp, Curvularia sp, and Mycoleptodiscus sp, displayed distinct antifungal activity against ≥3 tested fungi. To our knowledge, this is the first report of an endophytic community associated with C. inerme in China and its antifungal activity in vitro. PMID:26125809

  9. Evaluation of antifungal susceptibility testing in Candida isolates by Candifast and disk-diffusion method

    OpenAIRE

    Sidhartha Giri; Anupma Jyoti Kindo

    2014-01-01

    With the increase in invasive fungal infections due to Candida species and resistance to antifungal therapy, in vitro antifungal susceptibility testing is becoming an important part of clinical microbiology laboratories. Along with broth microdilution and disk diffusion method, various commercial methods are being increasingly used for antifungal susceptibility testing, especially in the developed world. In our study, we compared the antifungal susceptibility patterns of 39 isolates of Candid...

  10. ORIGINAL ARTICLE: Antifungal Activity of Some Natural Essential Oils against Candida Species Isolated from Blood Stream Infection

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    Amit Kumar

    2012-01-01

    Full Text Available Background: Candida is a part of normal microflora of human body and exists as an opportunistic pathogen as it attacks immunocompromised patients. Aims and Objectives: Candida is the most commonly isolated organism from blood stream infections. Fluconazole is the major antifungal drug used for treatment of Candida. Resistance to fluconazole has been increasing in recent years so there should be search of some other alternative. To find out these alternatives, anti candidial activity of some natural essential oils was studied. Materials and Methods: In the present study nine Candida strains isolated from blood stream infections were collected from National Culture Collection of Pathogenic Fungi (N.C.C.P.F. P.G.I.M.E.R Chandigarh India and the antifungal activity of some natural essential oils such as lemongrass oil, coconut oil, almond oil and clove oil was checked by using agar diffusion method. Result: All oils have shown a significantly anti-candidal activity. However, the antifungal activity was maximum in lemongrass oil. Conclusion: Our study may help to design new chemotherapeutic strategies against Candidal infections.

  11. Antitumor and Antifungal Activities of Organic Extracts of SeacucumberHolothuria atra from the Southeast Coast of India

    Institute of Scientific and Technical Information of China (English)

    Devaraj Isaac DHINAKARAN; Aaron Premnath LIPTON

    2015-01-01

    In phylum Echinodermata, the family Holothuridae is distinguished by its capacity of bioactive compounds. Sea cu-cumberHolothuria atra is commonly known as the lollyfish. The antifungal activity was detected using agar well diffusion method against the various fungal strains such asTrichoderma viride, Aspergillus niger,Aspergillus flavis,Candida albicansandPenicillium chrysogenum. Relatively high antifungal activity was seen againstCandida albicans at 100µL−1 concentration of extracts. Zone of inhibition was measured at 18mm of diameter. The anti-tumor activities were detected against the Vero and Hep2 cell lines using MTT assay. The cells were treated withH. atra extract at concentrations 0.078−10mgmL−1. The extract showed high proliferative activity against the Hep2 cells. The body wall extracts of sea cucumber (H. atra)showed effective antifungal and antitumor activities. All these findings suggest that the extracts could be used for the development of drugs.

  12. Survey of small antifungal peptides with chemotherapeutic potential.

    Science.gov (United States)

    Desbois, Andrew P; Tschörner, David; Coote, Peter J

    2011-08-01

    Many cationic peptides with antimicrobial properties have been isolated from bacteria, fungi, plants, and animals. These peptides vary in molecular size, potency and spectra of activities. This report surveyed the literature to highlight the peptides that have antifungal activity and greatest potential for development as new therapeutic agents. Thus, to be included in the evaluation, each peptide had to fulfil the following criteria: (i) potent antifungal activity, (ii) no, or minimal, mammalian cell toxicity, (iii) of ≤25 amino acids in length, which minimises the costs of synthesis, reduces immunogenicity and enhances bioavailability and stability in vivo, (iv) minimal post-translational modifications (also reduces the production costs). The ~80 peptides that satisfied these criteria are discussed with respect to their structures, mechanisms of antimicrobial action and in vitro and in vivo toxicities. Certainly, some of these small peptides warrant further study and have potential for future exploitation as new antifungal agents. PMID:21470150

  13. Antifungal activity of nicotine and its cobalt complex

    International Nuclear Information System (INIS)

    Nicotine and its metal complex; Co(II)-nicotine were isolated from leaves of Nicotiana tabacum using various metal ions by the reported techniques and studied for their antifungal activity against fourteen different species of fungi. For comparative study, pure sample of nicotine and metal salt used for complexation; cobalt(II) chloride was also subjected to antifungal tests with the same species of fungus under similar conditions. Results indicated that nicotine had antifungal activity against all species of fungi studied except Candida albicans, Microsporum canis, Epidermophyton floccosum, Candida tropicalis, and Alternaria infectoria. Cobalt(II) nicotine was found to be effective against all selected species of fungi but ineffective against Candida solani, Penicillium notalum, Microsporum canis, Fusarium solani and Fusarium moniliforme. (author)

  14. Antifungal Effect of Chitosan as Ca(2+) Channel Blocker.

    Science.gov (United States)

    Lee, Choon Geun; Koo, Ja Choon; Park, Jae Kweon

    2016-06-01

    The aim of this study was to investigate antifungal activity of a range of different molecular weight (MW) chitosan against Penicillium italicum. Our results demonstrate that the antifungal activity was dependent both the MW and concentration of the chitosan. Among a series of chitosan derived from the hydrolysis of high MW chitosan, the fractions containing various sizes of chitosan ranging from 3 to 15 glucosamine units named as chitooligomers-F2 (CO-F2) was found to show the highest antifungal activity against P. italicum. Furthermore, the effect of CO-F2 toward this fungus was significantly reduced in the presence of Ca(2+), whereas its effect was recovered by ethylenediaminetetraacetic acid, suggesting that the CO-F2 acts via disruption of Ca(2+) gradient required for survival of the fungus. Our results suggest that CO-F2 may serve as potential compounds to develop alternatives to synthetic fungicides for the control of the postharvest diseases. PMID:27298599

  15. Antifungal Effect of Chitosan as Ca2+ Channel Blocker

    Science.gov (United States)

    Lee, Choon Geun; Koo, Ja Choon; Park, Jae Kweon

    2016-01-01

    The aim of this study was to investigate antifungal activity of a range of different molecular weight (MW) chitosan against Penicillium italicum. Our results demonstrate that the antifungal activity was dependent both the MW and concentration of the chitosan. Among a series of chitosan derived from the hydrolysis of high MW chitosan, the fractions containing various sizes of chitosan ranging from 3 to 15 glucosamine units named as chitooligomers-F2 (CO-F2) was found to show the highest antifungal activity against P. italicum. Furthermore, the effect of CO-F2 toward this fungus was significantly reduced in the presence of Ca2+, whereas its effect was recovered by ethylenediaminetetraacetic acid, suggesting that the CO-F2 acts via disruption of Ca2+ gradient required for survival of the fungus. Our results suggest that CO-F2 may serve as potential compounds to develop alternatives to synthetic fungicides for the control of the postharvest diseases. PMID:27298599

  16. DMPD: C-type lectin receptors in antifungal immunity. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18160296 C-type lectin receptors in antifungal immunity. Willment JA, Brown GD. Tre...nds Microbiol. 2008 Jan;16(1):27-32. Epub 2007 Dec 21. (.png) (.svg) (.html) (.csml) Show C-type lectin receptors in anti...fungal immunity. PubmedID 18160296 Title C-type lectin receptors in antifungal immunity. Author

  17. In Vitro Interactions between Antifungals and Immunosuppressants against Aspergillus fumigatus Isolates from Transplant and Nontransplant Patients

    OpenAIRE

    Steinbach, William J.; Singh, Nina; Miller, Jackie L.; Benjamin, Daniel K; Schell, Wiley A.; Heitman, Joseph; Perfect, John R.

    2004-01-01

    We performed in vitro antifungal checkerboard testing on 12 Aspergillus fumigatus clinical isolates (6 transplant recipients and 6 nontransplant patients) with three antifungal agents (amphotericin B, voriconazole, and caspofungin) and three immunosuppressants (FK506, cyclosporine, and rapamycin). We were not able to detect a difference in calcineurin inhibitor antifungal activity against isolates from transplant recipients and nontransplant patients.

  18. Antifungal chemical compounds identified using a C. elegans pathogenicity assay.

    Directory of Open Access Journals (Sweden)

    Julia Breger

    2007-02-01

    Full Text Available There is an urgent need for the development of new antifungal agents. A facile in vivo model that evaluates libraries of chemical compounds could solve some of the main obstacles in current antifungal discovery. We show that Candida albicans, as well as other Candida species, are ingested by Caenorhabditis elegans and establish a persistent lethal infection in the C. elegans intestinal track. Importantly, key components of Candida pathogenesis in mammals, such as filament formation, are also involved in nematode killing. We devised a Candida-mediated C. elegans assay that allows high-throughput in vivo screening of chemical libraries for antifungal activities, while synchronously screening against toxic compounds. The assay is performed in liquid media using standard 96-well plate technology and allows the study of C. albicans in non-planktonic form. A screen of 1,266 compounds with known pharmaceutical activities identified 15 (approximately 1.2% that prolonged survival of C. albicans-infected nematodes and inhibited in vivo filamentation of C. albicans. Two compounds identified in the screen, caffeic acid phenethyl ester, a major active component of honeybee propolis, and the fluoroquinolone agent enoxacin exhibited antifungal activity in a murine model of candidiasis. The whole-animal C. elegans assay may help to study the molecular basis of C. albicans pathogenesis and identify antifungal compounds that most likely would not be identified by in vitro screens that target fungal growth. Compounds identified in the screen that affect the virulence of Candida in vivo can potentially be used as "probe compounds" and may have antifungal activity against other fungi.

  19. NLLSS: Predicting Synergistic Drug Combinations Based on Semi-supervised Learning.

    Science.gov (United States)

    Chen, Xing; Ren, Biao; Chen, Ming; Wang, Quanxin; Zhang, Lixin; Yan, Guiying

    2016-07-01

    Fungal infection has become one of the leading causes of hospital-acquired infections with high mortality rates. Furthermore, drug resistance is common for fungus-causing diseases. Synergistic drug combinations could provide an effective strategy to overcome drug resistance. Meanwhile, synergistic drug combinations can increase treatment efficacy and decrease drug dosage to avoid toxicity. Therefore, computational prediction of synergistic drug combinations for fungus-causing diseases becomes attractive. In this study, we proposed similar nature of drug combinations: principal drugs which obtain synergistic effect with similar adjuvant drugs are often similar and vice versa. Furthermore, we developed a novel algorithm termed Network-based Laplacian regularized Least Square Synergistic drug combination prediction (NLLSS) to predict potential synergistic drug combinations by integrating different kinds of information such as known synergistic drug combinations, drug-target interactions, and drug chemical structures. We applied NLLSS to predict antifungal synergistic drug combinations and showed that it achieved excellent performance both in terms of cross validation and independent prediction. Finally, we performed biological experiments for fungal pathogen Candida albicans to confirm 7 out of 13 predicted antifungal synergistic drug combinations. NLLSS provides an efficient strategy to identify potential synergistic antifungal combinations. PMID:27415801

  20. Isolation, Identification, and In Vitro Antifungal Susceptibility Testing of Dermatophytes from Clinical Samples at Sohag University Hospital in Egypt

    Science.gov (United States)

    Shalaby, Mona Fattouh Mohamed; El-din, Asmaa Nasr; El-Hamd, Mohammed Abu

    2016-01-01

    Aim The objective of this study was to isolate, identify, and explore the in-vitro antifungal susceptibility pattern of dermatophytes isolated from clinically suspected cases of dermatophytosis (tinea infections) attending the Dermatology Outpatient Clinic. Methods This study was conducted at Sohag University Hospital from December 2014 to December 2015. Clinical samples (e.g., skin scrapings and hair stumps) were collected under aseptic precautions. The identification of dermatophytes was performed through microscopic examination using 10% potassium hydroxide (KOH) with 40% dimethyl sulphoxide (DMSO) mounts and culture on Sabouraud dextrose agar (SDA) and on Dermasel agar base media, both supplemented with chloramphenicol and cycloheximide. All dermatophytes isolates were subjected to antifungal susceptibility testing using the agar-based disk diffusion (ABDD) method against Clotrimazole, Miconazole, Fluconazole, and Griseofulvin. Data were analyzed via SPSS 16, using Chi square and a screening test (cross-tabulation method). Results A total of 110 patients of dermatophytosis were studied. The patients were clinically diagnosed and mycologically confirmed as having tinea capitis (49), tinea corporis (30), tinea pedis (16), tinea cruris (9), or tinea barbae (6). The dermatophytes isolates belonged to 4 species: Microsporum canis 58 (52.7%), Microsporum gypseum 23 (20.9%), Trichophyton mentagrophytes 18 (16.4%), and Microsporum audouinii 11 (10%). The most effective antifungal drugs tested were Clotrimazole, followed by Miconazole (95.5% and 84.5% of isolates were susceptible, respectively). Conclusion Every patient with a tinea infection should be properly studied for a mycological examination and should be treated accordingly. Dermasel agar is more useful as an identification medium in the isolation of dermatophytes. The ABDD method appears to be a simple, cost-effective, and promising method for the evaluation of antifungal susceptibility of dermatophytes. PMID

  1. Speciation and antifungal susceptibility of esophageal candidiasis in cancer patients in a tertiary care hospital in South India

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    J. Abirami Lakshmy

    2016-01-01

    Full Text Available Esophageal candidiasis is the most common opportunistic infection in patients with altered immunity such as Human Immunodeficiency Virus (HIV infection, cancer patients on chemotherapy and radiotherapy. Neutropenia, irradiation and chemotherapy will facilitate deeper mucosal invasion leading to esophageal candidiasis. Empirical treatment of esophageal candidiasis without antifungal susceptibility testing will lead to the emergence of drug resistant species increasing the morbidity and mortality associated with cancer. The present study aimed to study the frequency of esophageal candida in individuals with cancer, species level identification and antifungal susceptibility pattern. Scrapings of whitish appearing lesions were obtained from a total of thirty five cases of endoscopically identified esophageal candidiasis were obtained from cancer patients. Identification of the Candida isolates were done by cultivation in Sabouraud dextrose agar (SDA, Gram staining, germ tube test, colony morphology in Chrom agar and corn meal agar, sugar assimilation and fermentation tests. Antifungal susceptibility was done by Microbroth dilution method for Fluconazole, Itraconazole and Amphotericin B. We found that Candida albicans was the predominant species isolated followed by Candida tropicalis and Candida glabrata. Sensitivity rates were 94%, 96% and 100% for Fluconazole, Itraconazole and Amphotericin B. Species level identification of Candida isolated from esophageal candidiasis and their antifungal sensitivity testing should be performed for early identification of resistant strains and for promptly treating the cases there by preventing the dissemination of infection in case of immune-compromised individuals. Further the susceptibility pattern will facilitate therapeutic guidance especially in individuals prone to relapse. [J Med Allied Sci 2016; 6(1: 29-34

  2. Antifungal activity of three mouth rinses--in vitro study.

    Science.gov (United States)

    Abirami, C P; Venugopal, Pankajalakshmi V

    2005-01-01

    Mouthrinses are nowadays routinely included in the home care oral hygiene maintenance besides dentifrice/tooth paste. Mouthrinses prevent bacterial attachment and prevent or slow down bacterial proliferation. Fungal organisms have now gained more importance due to increased incidence of AIDS/HIV. This has necessitated for mouthrinses to possess antifungal activity also. The mouthrinses used were Povidone iodine ( Wokadine), Thymol with Eucalyptol and Benzoic acid (Listerine) and fluoride with Triclosan (Colgate Plax), which were tested against oral isolates of different species of Candida. The agar diffusion test was used to evaluate the inhibitory activity of the mouthrinses and all of them exhibited antifungal activity especially against Candida albicans. PMID:16758789

  3. Antifungal activity of three mouth rinses--in vitro study.

    Science.gov (United States)

    Abirami, C P; Venugopal, Pankajalakshmi V

    2005-01-01

    Mouthrinses are nowadays routinely included in the home care oral hygiene maintenance besides dentifrice/tooth paste. Mouthrinses prevent bacterial attachment and prevent or slow down bacterial proliferation. Fungal organisms have now gained more importance due to increased incidence of AIDS/HIV. This has necessitated for mouthrinses to possess antifungal activity also. The mouthrinses used were Povidone iodine ( Wokadine), Thymol with Eucalyptol and Benzoic acid (Listerine) and fluoride with Triclosan (Colgate Plax), which were tested against oral isolates of different species of Candida. The agar diffusion test was used to evaluate the inhibitory activity of the mouthrinses and all of them exhibited antifungal activity especially against Candida albicans.

  4. Antifungal susceptibility profile of cryptic species of Aspergillus.

    Science.gov (United States)

    Alastruey-Izquierdo, Ana; Alcazar-Fuoli, Laura; Cuenca-Estrella, Manuel

    2014-12-01

    The use of molecular tools has led to the description of new cryptic species among different Aspergillus species complexes. Their frequency in the clinical setting has been reported to be between 10 and 15%. The susceptibility to azoles and amphotericin B of many of these species is low, and some of them, such as Aspergillus calidoustus or Aspergillus lentulus, are considered multi-resistant. The changing epidemiology, the frequency of cryptic species, and the different susceptibility profiles make antifungal susceptibility testing an important tool to identify the optimal antifungal agent to treat the infections caused by these species.

  5. Antifungal activity against postharvest fungi by extracts from Colombian propolis

    Directory of Open Access Journals (Sweden)

    Erick A. Meneses

    2009-01-01

    Full Text Available The aims of the present study were to evaluate the antifungal properties of Colombian propolis extracts against Colletotrichum gloeosporioides and Botryodiplodia theobromae, and to isolate and identify the main constituents from the active extracts. Therefore, propolis samples were thoroughly extracted with n-hexane/methanol (EPEM, dichloromethane, ethyl acetate, and methanol. Experimental results indicated that mycelial growth of all selected microorganisms was reduced in culture media containing EPEM and dichloromethane fractions. Furthermore, through antifungal bioassay-guided fractionation, three known labdane-type diterpenes: isocupressic acid (1, (+-agathadiol (2 and epi-13-torulosol (3 were isolated as the main constituents from the active fractions.

  6. Antifungal activity against postharvest fungi by extracts from Colombian propolis

    Energy Technology Data Exchange (ETDEWEB)

    Meneses, Erick A.; Durango, Diego L.; Garcia, Carlos M. [Universidad Nacional de Colombia, Medellin (Colombia). Facultad de Ciencias. Escuela de Quimica], e-mail: cmgarcia@unal.edu.co

    2009-07-01

    The aims of the present study were to evaluate the antifungal properties of Colombian propolis extracts against Colletotrichum gloeosporioides and Botryodiplodia theobromae, and to isolate and identify the main constituents from the active extracts. Therefore, propolis samples were thoroughly extracted with n-hexane/methanol (EPEM), dichloromethane, ethyl acetate, and methanol. Experimental results indicated that mycelial growth of all selected microorganisms was reduced in culture media containing EPEM and dichloromethane fractions. Furthermore, through antifungal bioassay-guided fractionation, three known labdane-type diterpenes: isocupressic acid (1), (+)-agathadiol (2) and epi-13-torulosol (3) were isolated as the main constituents from the active fractions. (author)

  7. ANTIFUNGAL ACTIVITY OF HYBANTHUS ENNEASPERMUS ON WET CLOTHES

    Directory of Open Access Journals (Sweden)

    Arumugam Napoleon

    2011-04-01

    Full Text Available During rainy season, when clothes are not properly dried they develop spots. In clothes the spots appear as black or greenish black in color and these spots or mildews were cultured and microscopically examined. It was identified as fungi, viz. Aspergillus niger, Aspergillus flavus and Aspergillus fumigatus. Antifungal activities of different extracts of Hybanthus enneaspermus were screened. The antifungal activity was graded, based on the zone of inhibition. Among the three extracts used for the present studies, methanolic extract exhibited the maximum growth inhibition, followed by chloroform and petroleum ether extract.

  8. Antifungal activity against postharvest fungi by extracts from Colombian propolis

    International Nuclear Information System (INIS)

    The aims of the present study were to evaluate the antifungal properties of Colombian propolis extracts against Colletotrichum gloeosporioides and Botryodiplodia theobromae, and to isolate and identify the main constituents from the active extracts. Therefore, propolis samples were thoroughly extracted with n-hexane/methanol (EPEM), dichloromethane, ethyl acetate, and methanol. Experimental results indicated that mycelial growth of all selected microorganisms was reduced in culture media containing EPEM and dichloromethane fractions. Furthermore, through antifungal bioassay-guided fractionation, three known labdane-type diterpenes: isocupressic acid (1), (+)-agathadiol (2) and epi-13-torulosol (3) were isolated as the main constituents from the active fractions. (author)

  9. Atmospheric pressure cold plasma as an antifungal therapy

    International Nuclear Information System (INIS)

    A microhollow cathode based, direct-current, atmospheric pressure, He/O2 (2%) cold plasma microjet was used to inactive antifungal resistants Candida albicans, Candida krusei, and Candida glabrata in air and in water. Effective inactivation (>90%) was achieved in 10 min in air and 1 min in water. Antifungal susceptibility tests showed drastic reduction of the minimum inhibitory concentration after plasma treatment. The inactivation was attributed to the reactive oxygen species generated in plasma or in water. Hydroxyl and singlet molecular oxygen radicals were detected in plasma-water system by electron spin resonance spectroscopy. This approach proposed a promising clinical dermatology therapy.

  10. Inhibition of human CYP19 by azoles used as antifungal agents and aromatase inhibitors, using a new LC-MS/MS method for the analysis of estradiol product formation

    International Nuclear Information System (INIS)

    Azoles are used as fungicides in agriculture or antifungal drugs in medicine. Their therapeutic activity is based on the inhibition of fungal lanosterol-14α-demethylase (CYP51). Azoles are also used for the treatment of estrogen-dependent diseases, e.g. in breast cancer therapy. Inhibition of CYP19 (aromatase) is the working principle for tumor therapy, but is an unwanted side effect of azoles used as fungicides or antifungal drugs. The inhibition of recombinant human CYP19 by 21 azoles in use for the three different purposes was investigated using the natural substrate testosterone. Estradiol product formation was measured by a newly developed and fully validated analytical method based on liquid chromatography-tandem mass spectrometry utilizing photospray ionization (APPI). Potency of enzyme inhibition was expressed in terms of IC5 concentrations. The two cytostatic drugs fadrozole and letrozole were the most potent inhibitors. However, azoles used as fungicides, e.g. prochloraz, or as antifungal drugs, e.g. bifonazole, were almost as potent inhibitors of aromatase as the drugs used in tumor therapy. Comparison of plasma concentrations that may be reached in antifungal therapy do not allow for large safety factors for bifonazole and miconazole. The IC5 values were compared to data obtained with other substrates, such as the pseudo-substrate dibenzylfluorescein (DBF). A high correlation was found, indicating that the fluorescence assay with DBF can well be used for potency ranking and screening of chemicals for aromatase inhibition. The data for antifungal drugs show that side effects on steroid hormone synthesis in humans due to inhibition of aromatase should be considered

  11. Advances in targeting the vacuolar proton-translocating ATPase (V-ATPase for anti-fungal therapy

    Directory of Open Access Journals (Sweden)

    Summer R. Hayek

    2014-01-01

    Full Text Available Vacuolar proton-translocating ATPase (V-ATPase is a membrane-bound, multi-subunit enzyme that uses the energy of ATP hydrolysis to pump protons across membranes. V-ATPase activity is critical for pH homeostasis and organelle acidification as well as for generation of the membrane potential that drives secondary transporters and cellular metabolism. V-ATPase is highly conserved across species and is best characterized in the model fungus Saccharomyces cerevisiae (S. cerevisiae. However, recent studies in mammals have identified significant alterations from fungi, particularly in the isoform composition of the 14 subunits and in the regulation of complex disassembly. These differences could be exploited for selectivity between fungi and humans and highlight the potential for V-ATPase as an anti-fungal drug target. Candida albicans (C. albicans is a major human fungal pathogen and causes fatality in 35% of systemic infections, even with anti-fungal treatment. The pathogenicity of C. albicans correlates with environmental, vacuolar, and cytoplasmic pH regulation, and V-ATPase appears to play a fundamental role in each of these processes. Genetic loss of V-ATPase in pathogenic fungi leads to defective virulence, and a comprehensive picture of the mechanisms involved is emerging. Recent studies have explored the practical utility of V-ATPase as an anti-fungal drug target in C. albicans, including pharmacological inhibition, azole therapy, and targeting of downstream pathways. This overview will discuss these studies as well as hypothetical ways to target V-ATPase and novel high-throughput methods for use in future drug discovery screens.

  12. Drug: D00323 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 3 Flucytosine (JP16/USP/INN) Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] D DERMATOLOGICALS D01 ANTIFUNGAL...S FOR DERMATOLOGICAL USE D01A ANTIFUNGALS FOR TOPICAL USE D01A

  13. Drug: D01664 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Steroid biosynthesis Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] D DERMATOLOGICALS D01 ANTIFUNGAL...S FOR DERMATOLOGICAL USE D01A ANTIFUNGALS FOR TOPICAL USE D01AC Imida

  14. Drug: D01046 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available cal (ATC) classification [BR:br08303] D DERMATOLOGICALS D01 ANTIFUNGALS FOR DERMATOLOGICAL USE D01A ANTIFU...NGALS FOR TOPICAL USE D01AE Other antifungals for topical use D01AE02 Methylrosanil

  15. Drug: D01094 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 1AA07 natural product Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] D DERMATOLOGICALS D01 ANTIFUNGAL...S FOR DERMATOLOGICAL USE D01A ANTIFUNGALS FOR TOPICAL USE D01AA Antib

  16. Drug: D00881 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available e (JAN/USP) Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] D DERMATOLOGICALS D01 ANTIFUNGAL...S FOR DERMATOLOGICAL USE D01A ANTIFUNGALS FOR TOPICAL USE D01AC Imidazole and t

  17. Drug: D02583 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 0100(K05917) Steroid biosynthesis Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] D DERMATOLOGICALS D01 ANTIFUNGAL...S FOR DERMATOLOGICAL USE D01A ANTIFUNGALS FOR TOPICAL USE

  18. Drug: D08245 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available hemical (ATC) classification [BR:br08303] D DERMATOLOGICALS D01 ANTIFUNGALS FOR D...ERMATOLOGICAL USE D01A ANTIFUNGALS FOR TOPICAL USE D01AE Other antifungals for topical use D01AE22 Naftifine

  19. Drug: D00886 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available azole nitrate (JAN/USP) Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] D DERMATOLOGICALS D01 ANTIFUNGAL...S FOR DERMATOLOGICAL USE D01A ANTIFUNGALS FOR TOPICAL USE D01AC Imi

  20. Drug: D00381 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available P/INN) Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] D DERMATOLOGICALS D01 ANTIFUNGALS F...OR DERMATOLOGICAL USE D01A ANTIFUNGALS FOR TOPICAL USE D01AE Other antifungals fo

  1. Drug: D01093 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ne hydrochloride (JP16/USAN) Anatomical Therapeutic Chemical (ATC) classification [BR:br08303] D DERMATOLOGICALS D01 ANTIFUNGAL...S FOR DERMATOLOGICAL USE D01A ANTIFUNGALS FOR TOPICAL USE D01A

  2. Antifungal testing and high-throughput screening of compound library against Geomyces destructans, the etiologic agent of geomycosis (WNS in bats.

    Directory of Open Access Journals (Sweden)

    Sudha Chaturvedi

    Full Text Available Bats in the northeastern U.S. are affected by geomycosis caused by the fungus Geomyces destructans (Gd. This infection is commonly referred to as White Nose Syndrome (WNS. Over a million hibernating bats have died since the fungus was first discovered in 2006 in a cave near Albany, New York. A population viability analysis conducted on little brown bats (Myotis lucifugus, one of six bat species infected with Gd, suggests regional extinction of this species within 20 years. The fungus Gd is a psychrophile ("cold loving", but nothing is known about how it thrives at low temperatures and what pathogenic attributes allow it to infect bats. This study aimed to determine if currently available antifungal drugs and biocides are effective against Gd. We tested five Gd strains for their susceptibility to antifungal drugs and high-throughput screened (HTS one representative strain with SpectrumPlus compound library containing 1,920 compounds. The results indicated that Gd is susceptible to a number of antifungal drugs at concentrations similar to the susceptibility range of human pathogenic fungi. Strains of Gd were susceptible to amphotericin B, fluconazole, itraconazole, ketoconazole and voriconazole. In contrast, very high MICs (minimum inhibitory concentrations of flucytosine and echinocandins were needed for growth inhibition, which were suggestive of fungal resistance to these drugs. Of the 1,920 compounds in the library, a few caused 50%--to greater than 90% inhibition of Gd growth. A number of azole antifungals, a fungicide, and some biocides caused prominent growth inhibition. Our results could provide a theoretical basis for future strategies aimed at the rehabilitation of most affected bat species and for decontamination of Gd in the cave environment.

  3. Azole Antifungal Sensitivity of Sterol 14α-Demethylase (CYP51) and CYP5218 from Malassezia globosa

    OpenAIRE

    Warrilow, Andrew G. S.; Price, Claire L.; Parker, Josie E.; Rolley, Nicola J.; Smyrniotis, Christopher J.; David D. Hughes; Vera Thoss; W. David Nes; Kelly, Diane E.; Holman, Theodore R.; Kelly, Steven L.

    2016-01-01

    Malassezia globosa cytochromes P450 CYP51 and CYP5218 are sterol 14α-demethylase (the target of azole antifungals) and a putative fatty acid metabolism protein (and a potential azole drug target), respectively. Lanosterol, eburicol and obtusifoliol bound to CYP51 with K d values of 32, 23 and 28 μM, respectively, catalyzing sterol 14α-demethylation with respective turnover numbers of 1.7 min−1, 5.6 min−1 and 3.4 min−1. CYP5218 bound a range of fatty acids with linoleic acid binding strongest ...

  4. 2-(Substituted phenyl-3,4-dihydroisoquinolin-2-iums as Novel Antifungal Lead Compounds: Biological Evaluation and Structure-Activity Relationships

    Directory of Open Access Journals (Sweden)

    Xin-Juan Yang

    2013-08-01

    Full Text Available The title compounds are a class of structurally simple analogues of quaternary benzo[c]phenanthridine alkaloids (QBAs. In order to develop novel QBA-like antifungal drugs, in this study, 24 of the title compounds with various substituents on the N-phenyl ring were evaluated for bioactivity against seven phytopathogenic fungi using the mycelial growth rate method and their SAR discussed. Almost all the compounds showed definite activities in vitro against each of the test fungi at 50 μg/mL and a broad antifungal spectrum. In most cases, the mono-halogenated compounds 2–12 exhibited excellent activities superior to the QBAs sanguinarine and chelerythrine. Compound 8 possessed the strongest activities on each of the fungi with EC50 values of 8.88–19.88 µg/mL and a significant concentration-dependent relationship. The SAR is as follows: the N-phenyl group is a high sensitive structural moiety for the activity and the characteristics and position of substituents intensively influence the activity. Generally, electron-withdrawing substituents remarkably enhance the activity while electron-donating substituents cause a decrease of the activity. In most cases, ortha- and para-halogenated isomers were more active than the corresponding m-halogenated isomers. Thus, the title compounds emerged as promising lead compounds for the development of novel biomimetic antifungal agrochemicals. Compounds 8 and 2 should have great potential as new broad spectrum antifungal agents for plant protection.

  5. Phylogeny of the clinically relevant species of the emerging fungus Trichoderma and their antifungal susceptibilities.

    Science.gov (United States)

    Sandoval-Denis, Marcelo; Sutton, Deanna A; Cano-Lira, José F; Gené, Josepa; Fothergill, Annette W; Wiederhold, Nathan P; Guarro, Josep

    2014-06-01

    A set of 73 isolates of the emerging fungus Trichoderma isolated from human and animal clinical specimens were characterized morphologically and molecularly using a multilocus sequence analysis that included the internal transcribed spacer (ITS) regions of the nuclear ribosomal DNA and fragments of the translation elongation factor 1 alpha (Tef1), endochitinase CHI18-5 (Chi18-5), and actin 1 (Act1) genes. The most frequent species was Trichoderma longibrachiatum (26%), followed by Trichoderma citrinoviride (18%), the Hypocrea lixii/Trichoderma harzianum species complex (15%), the newly described species Trichoderma bissettii (12%), and Trichoderma orientale (11%). The most common anatomical sites of isolation in human clinical specimens were the respiratory tract (40%), followed by deep tissue (30%) and superficial tissues (26%), while all the animal-associated isolates were obtained from superficial tissue samples. Susceptibilities of the isolates to eight antifungal drugs in vitro showed mostly high MICs, except for voriconazole and the echinocandins.

  6. Design, synthesis, and structure-activity relationship studies of benzothiazole derivatives as antifungal agents.

    Science.gov (United States)

    Zhao, Shizhen; Zhao, Liyu; Zhang, Xiangqian; Liu, Chunchi; Hao, Chenzhou; Xie, Honglei; Sun, Bin; Zhao, Dongmei; Cheng, Maosheng

    2016-11-10

    A series of compounds with benzothiazole and amide-imidazole scaffolds were designed and synthesized to combat the increasing incidence of drug-resistant fungal infections. The antifungal activity of these compounds was evaluated in vitro, and their structure-activity relationships (SARs) were evaluated. The synthesized compounds showed excellent inhibitory activity against Candida albicans and Cryptococcus neoformans. The most potent compounds 14o, 14p, and 14r exhibited potent activity, with minimum inhibitory concentration (MIC) values in the range of 0.125-2 μg/mL. Preliminary mechanism studies revealed that the compound 14p might act by inhibiting the CYP51 of Candida albicans. The SARs and binding mode established in this study are useful for further lead optimization. PMID:27494168

  7. Phenolic Compounds and Antifungal Activity of Hedera helix L. (Ivy Flowers and Fruits

    Directory of Open Access Journals (Sweden)

    Marcel PARVU

    2015-04-01

    Full Text Available Identification and quantitative analysis of the phenolic compounds from Hedera helix L. (ivy flower and fruit ethanol extracts by LC/MS, in vitro germination and growth inhibition effects on Aspergillus niger, Botrytis cinerea, Fusarium oxysporum f.sp. tulipae, Penicillium gladioli and Sclerotinia sclerotiorum were performed. In the non-hydrolyzed samples of flower and fruit extracts were determined, in different amounts, five polyphenols (p-coumaric acid, ferulic acid, rutoside, quercetol and kaempferol while quercitrin was identified only in the ivy flower extract. The hydrolyzed samples of the same ivy extracts indicated four phenolic compounds (p-coumaric acid, ferulic acid, quercetol and kaempferol, in different concentrations, whereas sinapic acid was only detected in the ivy fruit extract. The antifungal activity of the fresh flower extract was stronger than that of the fresh fruit extract and was compared to that of an antimycotic drug.

  8. Routine versus selective antifungal administration for control of fungal infections in patients with cancer

    DEFF Research Database (Denmark)

    Gøtzsche, Peter C; Johansen, Helle Krogh

    2014-01-01

    commonly used antifungal drugs decrease mortality in cancer patients with neutropenia. SEARCH METHODS: We searched PubMed from 1966 to 7 July 2014 and the reference lists of identified articles. SELECTION CRITERIA: Randomised clinical trials of amphotericin B, fluconazole, ketoconazole, miconazole....... Prophylactic or empirical treatment with amphotericin B significantly decreased total mortality (relative risk (RR) 0.69, 95% confidence interval (CI) 0.50 to 0.96), whereas the estimated RRs for fluconazole, ketoconazole, miconazole, and itraconazole were close to 1.00. No eligible trials were found...... with voriconazole. Amphotericin B and fluconazole decreased mortality ascribed to fungal infection (RR 0.45, 95% CI 0.26 to 0.76 and RR 0.42, 95% CI 0.24 to 0.73, respectively). The incidence of invasive fungal infection decreased significantly with administration of amphotericin B (RR 0.41, 95% CI 0.24 to 0...

  9. Antibacterial and antifungal screening of the root extracts of nardostachys jatamansi

    International Nuclear Information System (INIS)

    Antimicrobial activity of ethanol, ethyl acetate and hexane extracts of Nardostachys roots were studied in vitro against six pathogenic gram positive bacteria (Stayphylococcus aureus, streptococcus intermedius, S. faecalis, Bacillus Pumilus, B. cereus B. subtilus), six gram negative bacteria (Escherichia coli, Salmonella typhi, S. Paratyphi B, Klebsiella Pneumoniae, Proteus mirabilus, Shigella flexneri) and five fungi (Trichophyton rubrum, T. schoenleinii, Aspergillus niger, Candida albicans, C. glabrata). Ethanolic root extract exhibited maximum antimicrobial activity against all the tested bacteria and gungi, at concentration of 5, 10 and 20 mg/ml as compared to ethyl acetate and hexane extract, which did not show marked activity. Antimicrobial activity was compared with the activities of standard antibacterial and antifungal drugs, namely Ampicillin and Nystatin, respectively. The minimum inhibitory concentration (MIC) were between 0.5-1 mg/ml against all the studied microorganisms. (author)

  10. Repurposing the Clinically Efficacious Antifungal Agent Itraconazole as an Anticancer Chemotherapeutic.

    Science.gov (United States)

    Pace, Jennifer R; DeBerardinis, Albert M; Sail, Vibhavari; Tacheva-Grigorova, Silvia K; Chan, Kelly A; Tran, Raymond; Raccuia, Daniel S; Wechsler-Reya, Robert J; Hadden, M Kyle

    2016-04-28

    Itraconazole (ITZ) is an FDA-approved member of the triazole class of antifungal agents. Two recent drug repurposing screens identified ITZ as a promising anticancer chemotherapeutic that inhibits both the angiogenesis and hedgehog (Hh) signaling pathways. We have synthesized and evaluated first- and second-generation ITZ analogues for their anti-Hh and antiangiogenic activities to probe more fully the structural requirements for these anticancer properties. Our overall results suggest that the triazole functionality is required for ITZ-mediated inhibition of angiogenesis but that it is not essential for inhibition of Hh signaling. The synthesis and evaluation of stereochemically defined des-triazole ITZ analogues also provides key information as to the optimal configuration around the dioxolane ring of the ITZ scaffold. Finally, the results from our studies suggest that two distinct cellular mechanisms of action govern the anticancer properties of the ITZ scaffold. PMID:27014922

  11. Development of a Fluorescence-based Trypanosoma cruzi CYP51 Inhibition Assay for Effective Compound Triaging in Drug Discovery Programmes for Chagas Disease.

    Directory of Open Access Journals (Sweden)

    Jennifer Riley

    2015-09-01

    Full Text Available Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi, is a life threatening global health problem with only two drugs available for treatment (benznidazole and nifurtimox, both having variable efficacy in the chronic stage of the disease and high rates of adverse drug reactions. Inhibitors of sterol 14α-demethylase (CYP51 have proven effective against T. cruzi in vitro and in vivo in animal models of Chagas disease. Consequently two azole inhibitors of CYP51 (posaconazole and ravuconazole have recently entered clinical development by the Drugs for Neglected Diseases initiative. Further new drug treatments for this disease are however still urgently required, particularly having a different mode of action to CYP51 in order to balance the overall risk in the drug discovery portfolio. This need has now been further strengthened by the very recent reports of treatment failure in the clinic for both posaconazole and ravuconazole. To this end and to prevent enrichment of drug candidates against a single target, there is a clear need for a robust high throughput assay for CYP51 inhibition in order to evaluate compounds active against T. cruzi arising from phenotypic screens. A high throughput fluorescence based functional assay using recombinantly expressed T. cruzi CYP51 (Tulahuen strain is presented here that meets this requirement. This assay has proved valuable in prioritising medicinal chemistry resource on only those T. cruzi active series arising from a phenotypic screening campaign where it is clear that the predominant mode of action is likely not via inhibition of CYP51.

  12. Development of a Fluorescence-based Trypanosoma cruzi CYP51 Inhibition Assay for Effective Compound Triaging in Drug Discovery Programmes for Chagas Disease.

    Science.gov (United States)

    Riley, Jennifer; Brand, Stephen; Voice, Michael; Caballero, Ivan; Calvo, David; Read, Kevin D

    2015-09-01

    Chagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is a life threatening global health problem with only two drugs available for treatment (benznidazole and nifurtimox), both having variable efficacy in the chronic stage of the disease and high rates of adverse drug reactions. Inhibitors of sterol 14α-demethylase (CYP51) have proven effective against T. cruzi in vitro and in vivo in animal models of Chagas disease. Consequently two azole inhibitors of CYP51 (posaconazole and ravuconazole) have recently entered clinical development by the Drugs for Neglected Diseases initiative. Further new drug treatments for this disease are however still urgently required, particularly having a different mode of action to CYP51 in order to balance the overall risk in the drug discovery portfolio. This need has now been further strengthened by the very recent reports of treatment failure in the clinic for both posaconazole and ravuconazole. To this end and to prevent enrichment of drug candidates against a single target, there is a clear need for a robust high throughput assay for CYP51 inhibition in order to evaluate compounds active against T. cruzi arising from phenotypic screens. A high throughput fluorescence based functional assay using recombinantly expressed T. cruzi CYP51 (Tulahuen strain) is presented here that meets this requirement. This assay has proved valuable in prioritising medicinal chemistry resource on only those T. cruzi active series arising from a phenotypic screening campaign where it is clear that the predominant mode of action is likely not via inhibition of CYP51. PMID:26394211

  13. Antibacterial and antifungal activity of liriodenine and related oxoaporphine alkaloids.

    Science.gov (United States)

    Hufford, C D; Sharma, A S; Oguntimein, B O

    1980-10-01

    Liriodenine was evaluated for its antibacterial and antifungal activity against several microorganisms. Other related oxoaporphine alkaloids also were evaluated. Attempts to prepare oxoaporphine alkaloids from N-acetylnoraporphines were unsuccessful, but an unexpected phenanthrene alkaloid was obtained. A novel N-demethylation reaction was noted when oxogaucine methiodide and liriodenine methiodide were treated with alumina. PMID:7420287

  14. ANTIFUNGAL ACTIVITY OF GEOTHERMAL FLUIDS FROM DIFFERENT REGIONS OF TURKEY

    Directory of Open Access Journals (Sweden)

    Ahmet Ali Var,

    2012-07-01

    Full Text Available Antifungal effects of geothermal fluids obtained from the Ankara, Afyon, Denizli, and Eskişehir regions of Turkey on white-rot (Trametes versicolor, MAD-697 and brown-rot (Coniophora puteana, FPRL 11E fungus (Basidiomycetes were studied. Fungal experiments were performed on kraft paper and Scots pine wood (Pinus sylvestris L.. We used non-concentrated geothermal water and concentrated geothermal water (via evaporation in ratios of 25%, 50%, and 75%. To evaluate the results, we measured the concentration of specific minerals in the geothermal fluids such as boron (B, arsenic (As, copper (Cu, sulfate (SO4, sodium (Na, chloride (Cl, fluoride (F, potassium (K, and ammonia (NH3. The highest antifungal effect was observed for a geothermal fluid from the Denizli region, followed by Ankara, Afyon, and Eskişehir, in decreasing order. Antifungal properties of GFs are thought to be associated with the type and amount of mineral substances. In addition, the antifungal effects increased with increasing concentrations of geothermal water.

  15. Antifungal activity of heartwood extracts from three Juniperus species

    Science.gov (United States)

    Heartwood samples from three species of Juniperus (i.e., J. virginianna, J. occidentalis, and J. ashei) were extracted with hexane, ethanol and methanol and the hexane and ethanol extracts were tested for antifungal activity against four species of wood-rot fungi. These three species represent the ...

  16. In vitro antifungal activity of isavuconazole against Madurella mycetomatis

    NARCIS (Netherlands)

    W. Kloezen (Wendy); J.F. Meis (Jacques); I. Curfs-Breuker (Ilse); A.H. Fahal (Ahmed); W.W.J. van de Sande (Wendy)

    2012-01-01

    textabstractCurrently, therapy of black-grain mycetoma caused by Madurella mycetomatis consists of extensive debridement of the infected tissue combined with prolonged antifungal therapy with ketoconazole or itraconazole. In the present study, the in vitro activity of the new triazole isavuconazole

  17. In vitro antifungal activity of isavuconazole against Madurella mycetomatis.

    NARCIS (Netherlands)

    Kloezen, W.; Meis, J.F.G.M.; Curfs-Breuker, I.; Fahal, A.H.; Sande, W.W. van de

    2012-01-01

    Currently, therapy of black-grain mycetoma caused by Madurella mycetomatis consists of extensive debridement of the infected tissue combined with prolonged antifungal therapy with ketoconazole or itraconazole. In the present study, the in vitro activity of the new triazole isavuconazole toward M. my

  18. New small-size peptides possessing antifungal activity

    NARCIS (Netherlands)

    Garibotto, Francisco M.; Garro, Adriana D.; Masman, Marcelo F.; Rodriguez, Ana M.; Luiten, Paul G. M.; Raimondi, Marcela; Zacchino, Susana A.; Somlai, Csaba; Penke, Botond; Enriz, Ricardo D.

    2010-01-01

    The synthesis, in vitro evaluation, and conformational study of a new series of small-size peptides acting as antifungal agents are reported. In a first step of our study we performed a conformational analysis using Molecular Mechanics calculations. The electronic study was carried out using Molecul

  19. Therapeutic potential of antifungal plant and insect defensins

    NARCIS (Netherlands)

    Thevissen, K.; Kristensen, H.H.; Thomma, B.P.H.J.; Cammue, B.P.A.; François, I.E.J.A.

    2007-01-01

    To defend themselves against invading fungal pathogens, plants and insects largely depend on the production of a wide array of antifungal molecules, including antimicrobial peptides such as defensins. Interestingly, plant and insect defensins display antimicrobial activity not only against plant and

  20. Research to Identify Effective Antifungal Agents, 1992 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Schreck, Carl

    1993-03-01

    This study is a continuation of ``Research to Identify Effective Antifungal Agents'' sponsored by Bonneville Power Administration (Schreck et al. 1990 and Schreck et al. 1991). The objectives of the present study were to select and evaluate up to 10 candidate fungicides.