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Sample records for antimalarial quinoline methanols

  1. Design and Synthesis of Some New Quinoline Based 1,2,3-Triazoles as Antimicrobial and Antimalarial Agents

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    Parthasaradhi Y.

    2015-09-01

    Full Text Available A series of novel 6-bromo-2-chloro-3-(4-phenyl-[1,2,3]triazol-1-ylmethyl-quinoline and its derivatives (5a-j were synthesized in good yields from the intermediates (6-bromo-2-chloro-quinolin-3-yl-methanol (2, methanesulfonic acid (6-bromo-2-chloroquinolin-3-ylmethyl methanesulfonate (3 and 3-azidomethyl-6-bromo-2-chloro-quinoline (4. The synthetic route leading to the title compounds is commenced from commercially available 6-bromo-2-chloro-quinolin-3-carbaldehyde (1. The chemical structures of the newly synthesized compounds were elucidated by their IR, 1H and 13C NMR, mass spectral data and elemental analysis. Further, all the target compounds were screened for their antimicrobial activity against various microorganisms and antimalarial activity towards P. falciparum. DOI: http://dx.doi.org/10.17807/orbital.v7i3.692 

  2. The Oncolytic Efficacy and in Vivo Pharmacokinetics of [2-(4-Chlorophenyl)quinolin-4-yl](piperidine-2-yl)methanol (Vacquinol-1) Are Governed by Distinct Stereochemical Features.

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    Hammarström, Lars G J; Harmel, Robert K; Granath, Mikael; Ringom, Rune; Gravenfors, Ylva; Färnegårdh, Katarina; Svensson, Per H; Wennman, David; Lundin, Göran; Roddis, Ylva; Kitambi, Satish S; Bernlind, Alexandra; Lehmann, Fredrik; Ernfors, Patrik

    2016-09-22

    Glioblastoma remains an incurable brain cancer. Drugs developed in the past 20 years have not improved the prognosis for patients, necessitating the development of new treatments. We have previously reported the therapeutic potential of the quinoline methanol Vacquinol-1 (1) that targets glioblastoma cells and induces cell death by catastrophic vacuolization. Compound 1 is a mixture of four stereoisomers due to the two adjacent stereogenic centers in the molecule, complicating further development in the preclinical setting. This work describes the isolation and characterization of the individual isomers of 1 and shows that these display stereospecific pharmacokinetic and pharmacodynamic features. In addition, we present a stereoselective synthesis of the active isomers, providing a basis for further development of this compound series into a novel experimental therapeutic for glioblastoma. PMID:27607569

  3. Effect of antimalarial drugs on stimulation and interleukin 2 production of human lymphocytes

    DEFF Research Database (Denmark)

    Bygbjerg, I C; Svenson, M; Theander, T G;

    1987-01-01

    Effect of pyrimethamine, an antimalarial antifolate, and of mefloquine, chloroquine, and quinine, which belong to the quinoline group of antimalarials, on proliferation and interleukin 2 (IL-2) production of human lymphocytes was studied in vitro. Pyrimethamine at concentrations above therapeutic...... levels suppressed the lymphocytes' proliferation, but not their IL-2 production. All three quinolines suppressed the proliferation of lymphocytes, but not equally, with mefloquine having the strongest effect. Quinine suppressed the growth at therapeutic concentrations. The IL-2 production was suppressed...

  4. Quinine conjugates and quinine analogues as potential antimalarial agents.

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    Jones, Rachel A; Panda, Siva S; Hall, C Dennis

    2015-06-01

    Malaria is a tropical disease, prevalent in Southeast Asia and Africa, resulting in over half a million deaths annually; efforts to develop new antimalarial agents are therefore particularly important. Quinine continues to play a role in the fight against malaria, but quinoline derivatives are more widely used. Drugs based on the quinoline scaffold include chloroquine and primaquine, which are able to act against the blood and liver stages of the parasite's life cycle. The purpose of this review is to discuss reported biologically active compounds based on either the quinine or quinoline scaffold that may have enhanced antimalarial activity. The review emphasises hybrid molecules, and covers advances made in the last five years. The review is divided into three sections: modifications to the quinine scaffold, modifications to aminoquinolines and finally metal-containing antimalarial compounds.

  5. Antimalarial peroxides

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    DEJAN M. OPSENICA

    2009-11-01

    Full Text Available The problem of endemic malaria continues unabated globally. Malaria affects 40 % of the global population, causing an estimated annual mortality of 1.5–2.7 million people. The World Health Organization (WHO estimates that 90 % of these deaths occur in sub-Saharan Africa among infants under the age of five. While a vaccine against malaria continues to be elusive, chemotherapy remains the most viable alternative towards treatment of the disease. During last years, the situation has become urgent in many ways, but mainly because of the development of chloroquine-resistant (CQR strains of Plasmodium falciparum (Pf. The discovery that artemisinin (ART, 1, an active principle of Artemisia annua L., expresses a significant antimalarial activity, especially against CQR strains, opened new approaches for combating malaria. Since the early 1980s, hundreds of semisynthetic and synthetic peroxides have been developed and tested for their antimalarial activity, the results of which were extensively reviewed. In addition, in therapeutic practice, there is no reported case of drug resistance to these antimalarial peroxides. This review summarizes recent achievements in the area of peroxide drug development for malaria chemotherapy.

  6. Wet oxidation of quinoline

    DEFF Research Database (Denmark)

    Thomsen, A.B.; Kilen, H.H.

    1998-01-01

    time was less important within the range studied. Nitrifying bacteria were used to measure the inhibition from wet oxidative-treated samples to study the effect of the (wet oxidation) reaction conditions. Wet oxidation made quinoline more toxic to Nitrosomonas. This was observed for Nitrobacter as well......The influence of oxygen pressure (0.4 and 2 MPa). reaction time (30 and 60 min) and temperature (260 and 280 degrees C) on the wet oxidation of quinoline has been studied. The dominant parameters for the decomposition of quinoline were oxygen pressure and reaction temperature. whereas the reaction....... The combined wet oxidation and biological treatment of reaction products resulted in 91% oxidation of the parent compound to CO2 and water. Following combined wet oxidation and biological treatment the sample showed low toxicity towards Nitrosomonas and no toxicity towards Nitrobacter. (C) 1998 Elsevier...

  7. Antimalarial activity of extracts of Malaysian medicinal plants.

    Science.gov (United States)

    Najib Nik A Rahman, N; Furuta, T; Kojima, S; Takane, K; Ali Mohd, M

    1999-03-01

    In vitro and in vivo studies revealed that Malaysian medicinal plants, Piper sarmentosum, Andrographis paniculata and Tinospora crispa produced considerable antimalarial effects. Chloroform extract in vitro did show better effect than the methanol extract. The chloroform extract showed complete parasite growth inhibition as low as 0.05 mg/ml drug dose within 24 h incubation period (Andrographis paniculata) as compared to methanol extract of drug dose of 2.5 mg/ml but under incubation time of 48 h of the same plant spesies. In vivo activity of Andrographis paniculata also demonstrated higher antimalarial effect than other two plant species. PMID:10363840

  8. On peroxide antimalarials

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    IGOR OPSENICA

    2007-12-01

    Full Text Available Several dicyclohexylidene tetraoxanes were prepared in order to gain a further insight into structure–activity relationship of this kind of antimalarials. The tetraoxanes 2–5, obtained as a cis/trans mixture, showed pronounced antimalarial activity against Plasmodium falciparum chloroquine susceptible D6, chloroquine resistant W2 and multidrug-resistant TM91C235 (Thailand strains. They have better than or similar activity to the corresponding desmethyl dicyclohexylidene derivatives. Two chimeric endoperoxides with superior antimalarial activity to the natural product ascaridole were also synthesized.

  9. Hydrodenitrogenation of quinoline and acridine

    Energy Technology Data Exchange (ETDEWEB)

    Reiff, Jr., E. K.

    1977-06-01

    The hydrodenitrogenation of quinoline and of acridine was studied in a batch autoclave reactor between 342 and 353/sup 0/C and between 500 and 2000 psig. The several commercial hydrotreating catalysts examined decreased in activity in the following order for quinoline hydrodenitrogenation: Ni--Mo/Al/sub 2/O/sub 3/, Ni--W/Al/sub 2/O/sub 3/, Ni--W/SiO/sub 2/--Al/sub 2/O/sub 3/, and Co--Mo/Al/sub 2/O/sub 3/. The total nitrogen removal rate for quinoline was slightly greater than that for acridine and both followed pseudo first-order kinetics over a conversion range of 0 to 50%. Hydrogenation and cracking steps were both kinetically limiting. Nitrogen-containing reaction products for quinoline hydrodenitrogenation were 1,2,3,4-tetrahydroquinoline, 5,6,7,8-tetrahydroquinoline, decahydroquinoline and o-propylaniline. At 342/sup 0/C and 500 psig quinoline and 1,2,3,4-tetrahydroquinoline were in thermodynamic equilibrium, and the disappearance of the lumped group of quinoline plus 1,2,3,4-tetrahydroquinoline followed pseudo first-order kinetics. Sixteen nitrogen-containing reaction products were found for acridine hydrodenitrogenation, including 1,2,3,4-tetrahydroacridine, 1,2,3,4,9,10,13,14-octahydroacridine, sym-octahydroacridine, perhydroacridine, and o-(methylenecyclohexane)aniline. The hydrogenolysis step for both quinoline and acridine appears to be through hydrogenated forms of these compounds. This is supported by bond strength arguments.

  10. Preliminary assessment of medicinal plants used as antimalarials in the southeastern Venezuelan Amazon

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    Caraballo Alejandro

    2004-01-01

    Full Text Available Eighteen species of medicinal plants used in the treatment of malaria in Bolívar State, Venezuela were recorded and they belonged to Compositae, Meliaceae, Anacardiaceae, Bixaceae, Boraginaceae, Caricaceae, Cucurbitaceae, Euphorbiaceae, Leguminosae, Myrtaceae, Phytolaccaceae, Plantaginaceae, Scrophulariaceae, Solanaceae and Verbenaceae families. Antimalarial plant activities have been linked to a range of compounds including anthroquinones, berberine, flavonoids, limonoids, naphthquinones, sesquiterpenes, quassinoids, indol and quinoline alkaloids.

  11. Cajachalcone: An Antimalarial Compound from Cajanus cajan Leaf Extract.

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    Ajaiyeoba, E O; Ogbole, O O; Abiodun, O O; Ashidi, J S; Houghton, P J; Wright, C W

    2013-01-01

    Cajanus cajan L, a member of the family Fabaceae, was identified from the Nigerian antimalarial ethnobotany as possessing antimalarial properties. The bioassay-guided fractionation of the crude methanol extract of C. cajan leaves was done in vitro using the multiresistant strain of Plasmodium falciparum (K1) in the parasite lactate dehydrogenase assay. Isolation of compound was achieved by a combination of chromatographic techniques, while the structure of the compound was elucidated by spectroscopy. This led to the identification of a cajachalcone, 2',6'-dihydroxy-4-methoxy chalcone, as the biologically active constituent from the ethyl acetate fraction. Cajachalcone had an IC50 value of 2.0  μ g/mL (7.4  μ M) and could be a lead for anti-malarial drug discovery. PMID:23970954

  12. Cajachalcone: An Antimalarial Compound from Cajanus cajan Leaf Extract

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    E. O. Ajaiyeoba

    2013-01-01

    Full Text Available Cajanus cajan L, a member of the family Fabaceae, was identified from the Nigerian antimalarial ethnobotany as possessing antimalarial properties. The bioassay-guided fractionation of the crude methanol extract of C. cajan leaves was done in vitro using the multiresistant strain of Plasmodium falciparum (K1 in the parasite lactate dehydrogenase assay. Isolation of compound was achieved by a combination of chromatographic techniques, while the structure of the compound was elucidated by spectroscopy. This led to the identification of a cajachalcone, 2′,6′-dihydroxy-4-methoxy chalcone, as the biologically active constituent from the ethyl acetate fraction. Cajachalcone had an IC50 value of 2.0 μg/mL (7.4 μM and could be a lead for anti-malarial drug discovery.

  13. Antimalarial activity of cedronin.

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    Moretti, C; Deharo, E; Sauvain, M; Jardel, C; David, P T; Gasquet, M

    1994-06-01

    Cedronin was isolated from Simaba cedron Planchon (Simaroubaceae), a species popularly believed in South America to have antimalarial properties. It was examined for in vitro and in vivo antimalarial activities and for cytotoxicity against KB cells. Experimental results showed that cedronin was active against chloroquine-sensitive and resistant strain, with an IC50 of 0.25 micrograms/ml (0.65 mumol/ml). It was also found to be active in vivo against Plasmodium vinkei with an IC50 of 1.8 mg/kg (4.7 nM/kg) in the classic 4-day test. Cedronin belongs to the small group of quassinoids with a C19 basic skeleton and shows a rather low cytotoxicity against KB cells (IC50 = 4 micrograms/ml, 10.4 microM) as compared with C20 biologically active quassinoids; however its toxic/therapeutic ratio (10/1.8) remains lower than chloroquine (10/0.5).

  14. Methyl 3-(Quinolin-2-ylindolizine-1-carboxylate

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    Roumaissa Belguedj

    2015-12-01

    Full Text Available A novel compound, methyl 3-(quinolin-2-ylindolizine-1-carboxylate (2 has been synthesized by cycloaddition reaction of 1-(quinolin-2-ylmethylpyridinium ylide (1 with methyl propiolate in presence of sodium hydride in THF. The structure of this compound was established by IR, 1H-NMR, 13C-NMR and MS data

  15. Amazonian Plant Natural Products: Perspectives for Discovery of New Antimalarial Drug Leads

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    Lucio H. Freitas-Junior

    2013-08-01

    Full Text Available Plasmodium falciparum and P. vivax malaria parasites are now resistant, or showing signs of resistance, to most drugs used in therapy. Novel chemical entities that exhibit new mechanisms of antiplasmodial action are needed. New antimalarials that block transmission of Plasmodium spp. from humans to Anopheles mosquito vectors are key to malaria eradication efforts. Although P. vivax causes a considerable number of malaria cases, its importance has for long been neglected. Vivax malaria can cause severe manifestations and death; hence there is a need for P. vivax-directed research. Plants used in traditional medicine, namely Artemisia annua and Cinchona spp. are the sources of the antimalarial natural products artemisinin and quinine, respectively. Based on these compounds, semi-synthetic artemisinin-derivatives and synthetic quinoline antimalarials have been developed and are the most important drugs in the current therapeutic arsenal for combating malaria. In the Amazon region, where P. vivax predominates, there is a local tradition of using plant-derived preparations to treat malaria. Here, we review the current P. falciparum and P. vivax drug-sensitivity assays, focusing on challenges and perspectives of drug discovery for P. vivax, including tests against hypnozoites. We also present the latest findings of our group and others on the antiplasmodial and antimalarial chemical components from Amazonian plants that may be potential drug leads against malaria.

  16. Complex polymorphisms in the Plasmodium falciparum multidrug resistance protein 2 gene and its contribution to antimalarial response.

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    Veiga, Maria Isabel; Osório, Nuno S; Ferreira, Pedro Eduardo; Franzén, Oscar; Dahlstrom, Sabina; Lum, J Koji; Nosten, Francois; Gil, José Pedro

    2014-12-01

    Plasmodium falciparum has the capacity to escape the actions of essentially all antimalarial drugs. ATP-binding cassette (ABC) transporter proteins are known to cause multidrug resistance in a large range of organisms, including the Apicomplexa parasites. P. falciparum genome analysis has revealed two genes coding for the multidrug resistance protein (MRP) type of ABC transporters: Pfmrp1, previously associated with decreased parasite drug susceptibility, and the poorly studied Pfmrp2. The role of Pfmrp2 polymorphisms in modulating sensitivity to antimalarial drugs has not been established. We herein report a comprehensive account of the Pfmrp2 genetic variability in 46 isolates from Thailand. A notably high frequency of 2.8 single nucleotide polymorphisms (SNPs)/kb was identified for this gene, including some novel SNPs. Additionally, we found that Pfmrp2 harbors a significant number of microindels, some previously not reported. We also investigated the potential association of the identified Pfmrp2 polymorphisms with altered in vitro susceptibility to several antimalarials used in artemisinin-based combination therapy and with parasite clearance time. Association analysis suggested Pfmrp2 polymorphisms modulate the parasite's in vitro response to quinoline antimalarials, including chloroquine, piperaquine, and mefloquine, and association with in vivo parasite clearance. In conclusion, our study reveals that the Pfmrp2 gene is the most diverse ABC transporter known in P. falciparum with a potential role in antimalarial drug resistance. PMID:25267670

  17. Complex polymorphisms in the Plasmodium falciparum multidrug resistance protein 2 gene and its contribution to antimalarial response.

    Science.gov (United States)

    Veiga, Maria Isabel; Osório, Nuno S; Ferreira, Pedro Eduardo; Franzén, Oscar; Dahlstrom, Sabina; Lum, J Koji; Nosten, Francois; Gil, José Pedro

    2014-12-01

    Plasmodium falciparum has the capacity to escape the actions of essentially all antimalarial drugs. ATP-binding cassette (ABC) transporter proteins are known to cause multidrug resistance in a large range of organisms, including the Apicomplexa parasites. P. falciparum genome analysis has revealed two genes coding for the multidrug resistance protein (MRP) type of ABC transporters: Pfmrp1, previously associated with decreased parasite drug susceptibility, and the poorly studied Pfmrp2. The role of Pfmrp2 polymorphisms in modulating sensitivity to antimalarial drugs has not been established. We herein report a comprehensive account of the Pfmrp2 genetic variability in 46 isolates from Thailand. A notably high frequency of 2.8 single nucleotide polymorphisms (SNPs)/kb was identified for this gene, including some novel SNPs. Additionally, we found that Pfmrp2 harbors a significant number of microindels, some previously not reported. We also investigated the potential association of the identified Pfmrp2 polymorphisms with altered in vitro susceptibility to several antimalarials used in artemisinin-based combination therapy and with parasite clearance time. Association analysis suggested Pfmrp2 polymorphisms modulate the parasite's in vitro response to quinoline antimalarials, including chloroquine, piperaquine, and mefloquine, and association with in vivo parasite clearance. In conclusion, our study reveals that the Pfmrp2 gene is the most diverse ABC transporter known in P. falciparum with a potential role in antimalarial drug resistance.

  18. Difluoro[2-(quinolin-2-ylphenolato]borane

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    Xi Yang

    2011-05-01

    Full Text Available The title compound, C15H10BF2NO, was synthesized by the reaction of 2-(quinolin-2-ylphenol and boron trifluoride etherate. The quinoline ring system and the benzene ring are twisted, making a dihedral angle of 8.3 (2°. In the crystal, π–π interactions between the aromatic rings [centroid–centroid distance = 3.638 (9 Å] link the molecules into chains propagating in [100].

  19. Antimalarial activity of extracts and alkaloids isolated from six plants used in traditional medicine in Mali and Sao Tome.

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    Ancolio, C; Azas, N; Mahiou, V; Ollivier, E; Di Giorgio, C; Keita, A; Timon-David, P; Balansard, G

    2002-11-01

    Methanol and chloroform extracts were prepared from various parts of four plants collected in Mali: Guiera senegalensis (Gmel.) Combretaceae, Feretia apodanthera (Del.) Rubiaceae, Combretum micranthum (Don.) Combretaceae, Securidaca longepedunculata (Fres.) Polygalaceae and two plants -collected in Sao Tome: Pycnanthus angolensis (Welw.) Myristicaceae and Morinda citrifolia (Benth.) Rubiaceae were assessed for their in vitro antimalarial activity and their cytotoxic effects on human monocytes (THP1 cells) by flow cytometry. The methanol extract of leaves of Feretia apodanthera and the chloroform extract of roots of Guiera senegalensis exhibited a pronounced antimalarial activity. Two alkaloids isolated from the active extract of Guiera senegalensis, harman and tetrahydroharman, showed antimalarial activity (IC(50) lower than 4 microg/mL) and displayed low toxicity against THP1. Moreover, the decrease of THP1 cells in S phase of the cell cycle, after treatment with harman and tetrahydroharman, was probably due to an inhibition of total protein synthesis. PMID:12410545

  20. Antimicrobial and antimalarial properties of medicinal plants used by the indigenous tribes of Andaman and Nicobar Islands, India.

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    Chander, M Punnam; Pillai, C R; Sunish, I P; Vijayachari, P

    2016-07-01

    In this study, methanol extracts of six medicinal plants (Alstonia macrophylla, Claoxylon indicum, Dillenia andamanica, Jasminum syringifolium, Miliusia andamanica and Pedilanthus tithymaloides) traditionally used by Nicobarese tribes of Andaman and Nicobar Islands were studied for antimicrobial and antimalarial activities as well as preliminary photochemical analysis. Plants were collected from Car Nicobar of Andaman and Nicobar Islands and the ethnobotanical data were gathered from traditional healers who inhabit the study area. The methanol extracts were obtained by cold percolation method and the antimicrobial activity was found using agar well diffusion method. Among the plants tested, J. syringifolium, D. andamanica, C. indicum were most active. The antimalarial activity was evaluated against Plasmodium falciparum chloroquine-sensitive MRC-2 isolate. The crude extract of M. andamanica showed excellent antimalarial activity followed by extracts of P. tithymaloides, J. syringifolium and D. andamanica. The chemical injury to erythrocytes was also carried out and it showed that, there were no morphological changes in erythrocytes by the methanol crude extracts. The in vitro antimicrobial and antimalarial activity might be due to the presence of alkaloids, flavonoids, triterpenes, sterols, tannins and saponins in the methanol extracts of tested plants. PMID:27174207

  1. Cannizzaro reaction of 2-chloro-3-formylquinolines and its synthetic utility for 2-acetylfuro[2,3-]quinolines: The alkaloid analogues

    Indian Academy of Sciences (India)

    Devadoss Karthik Kumar; Rajakandhan Shankar; Subramaniam Parameswaran Rajendran

    2012-09-01

    Cannizzaro reaction of 2-chloro-3-formylquinolines was investigated under two different conditions. Under both conditions, redox and methoxylation proceeded simultaneously and gave 2-methoxy- 3-formylquinolines, 2-methoxyquinolin-3-yl-methanols and 2-methoxyquinoline-3-carboxylic acids. The synthesized 2-methoxy-3-formylquinolines were then condensed with acetone in the presence of sulphuric acid to give 4-(2-methoxy-quinolin-3-yl)-but-3-en-2-ones which in turn were bromocyclized and dehydrobrominated to get 2-acetylfuro[2,3-]quinolines.

  2. Dissociative photoionization of quinoline and isoquinoline

    NARCIS (Netherlands)

    J. Bouwman; B. Sztáray; J. Oomens; P. Hemberger; A. Bodi

    2015-01-01

    Two nitrogen-containing polycyclic aromatic hydrocarbon isomers of C9H7N composition, quinoline, and isoquinoline have been studied by imaging photoelectron photoion coincidence spectroscopy at the VUV beamline of the Swiss Light Source. High resolution threshold photoelectron spectra have been reco

  3. Antimalarial natural products: a review

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    Faraz Mojab

    2012-03-01

    Results and Conclusion: There is an urgent need for the development of new treatments for malaria. Many countries have a vast precedence in the use of medicinal plants and the required knowledge spans many centuries. Although malaria is controlled in Iran, some researchers tend to study malaria and related subjects. In vitro biological tests for the detection of antimalarial activities in plant extracts are currently available. It is vital that the efficacy and safety of traditional medicines be validated and their active constituents be identified in order to establish reliable quality control measures.

  4. In vitro and in vivo assessment of the anti-malarial activity of Caesalpinia pluviosa

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    Eberlin Marcos N

    2011-05-01

    Full Text Available Abstract Background To overcome the problem of increasing drug resistance, traditional medicines are an important source for potential new anti-malarials. Caesalpinia pluviosa, commonly named "sibipiruna", originates from Brazil and possess multiple therapeutic properties, including anti-malarial activity. Methods Crude extract (CE was obtained from stem bark by purification using different solvents, resulting in seven fractions. An MTT assay was performed to evaluate cytotoxicity in MCF-7 cells. The CE and its fractions were tested in vitro against chloroquine-sensitive (3D7 and -resistant (S20 strains of Plasmodium falciparum and in vivo in Plasmodium chabaudi-infected mice. In vitro interaction with artesunate and the active C. pluviosa fractions was assessed, and mass spectrometry analyses were conducted. Results At non-toxic concentrations, the 100% ethanolic (F4 and 50% methanolic (F5 fractions possessed significant anti-malarial activity against both 3D7 and S20 strains. Drug interaction assays with artesunate showed a synergistic interaction with the F4. Four days of treatment with this fraction significantly inhibited parasitaemia in mice in a dose-dependent manner. Mass spectrometry analyses revealed the presence of an ion corresponding to m/z 303.0450, suggesting the presence of quercetin. However, a second set of analyses, with a quercetin standard, showed distinct ions of m/z 137 and 153. Conclusions The findings show that the F4 fraction of C. pluviosa exhibits anti-malarial activity in vitro at non-toxic concentrations, which was potentiated in the presence of artesunate. Moreover, this anti-malarial activity was also sustained in vivo after treatment of infected mice. Finally, mass spectrometry analyses suggest that a new compound, most likely an isomer of quercetin, is responsible for the anti-malarial activity of the F4.

  5. New quinoline alkaloid from Ruta graveolens aerial parts and evaluation of the antifertility activity.

    Science.gov (United States)

    Salib, Josline Y; El-Toumy, Sayed A; Hassan, Emad M; Shafik, Nabila H; Abdel-Latif, Sally M; Brouard, Ignacio

    2014-01-01

    Bioassay-guided isolation of methanol extract of Ruta graveolens L. leaves yielded a new quinoline alkaloid, (4S) 1,4-dihydro-4-methoxy-1,4-dimethyl-3-(3-methylbut-2-enyl)quinoline 2,7-diol, and nine phenolic compounds including rutin as a major compound. Structures of the isolated compounds were determined by using chromatography, UV, HR-ESI-MS and 1D/2D (1)H/(13)C NMR spectroscopy. The uterotonic activity of methanol extract fractions (ethyl acetate, n-butanol and aqueous fraction) as well as the isolated major compounds was tested in the isolated mouse uterus in vitro. The n-butanol-soluble fraction was found to demonstrate the most potent uterotonic activity in a dose-dependent manner, also the major isolated compound rutin revealed the occurrence of an uterotonic response, which was maximum at a concentration level of 0.25 mg/mL, accounting for 68.7% of that exhibited by the chosen concentration of oxytocin.

  6. trans-Dichloridobis(quinoline-κNplatinum(II

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    Kwang Ha

    2012-05-01

    Full Text Available In the title complex, trans-[PtCl2(C9H7N2], the PtII ion is four-coordinated in an essentially square-planar coordination environment defined by two N atoms from two quinoline (qu ligands and two Cl− anions. The Pt atom is located on an inversion centre and thus the asymmetric unit contains one half of the complex; the PtN2Cl2 unit is exactly planar. The dihedral angle between the PtN2Cl2 unit and the quinoline ligand is 85.1 (1°. In the crystal, the complex molecules are stacked into columns along the b axis. In the columns, several intermolecular π–π interactions between the six-membered rings are present, the shortest ring centroid–centroid distance being 3.733 (5 Å between pyridine rings.

  7. Pricing, distribution, and use of antimalarial drugs.

    OpenAIRE

    Foster, S. D.

    1991-01-01

    Prices of new antimalarial drugs are targeted at the "travellers' market" in developed countries, which makes them unaffordable in malaria-endemic countries where the per capita annual drug expenditures are US$ 5 or less. Antimalarials are distributed through a variety of channels in both public and private sectors, the official malaria control programmes accounting for 25-30% of chloroquine distribution. The unofficial drug sellers in markets, streets, and village shops account for as much a...

  8. Antimalarial and cytotoxic properties of Chukrasia tabularis A. Juss and Turraea vogelii Hook F. Ex. Benth.

    Science.gov (United States)

    Ogbole, Omonike O; Saka, Yusuf A; Fasinu, Pius S; Fadare, Adenike A; Ajaiyeoba, Edith O

    2016-04-01

    Malaria, caused by plasmodium parasite, is at the moment the highest cause of morbidity and mortality in the tropics. Recently, there is increasing efforts to develop more potent antimalarials from plant sources that will have little or no adverse effects. This study is aimed at investigating the in vivo mice antimalarial and in vitro antiplasmodial effects of two Meliaceae plants commonly used in Nigerian ethnomedicine as part of recipe for treating malaria infection: Chukrasia tabularis and Turraea vogelii. Hot water decoction and methanol extract of both plants were evaluated for their antimalarial activity in vivo using the mice model assay and in vitro using the parasite lactate dehydrogenase (pLDH) assay. The extracts were also assessed for toxicity with brine shrimp lethality assay and in mammalian cell lines using the neural red assay. The in vivo mice model antimalarial study showed that the methanol extract of the stem bark of C. tabularis exhibited the highest % chemosuppression (83.65 ± 0.66) at the highest dosage administered (800 mg/kg) when compared with chloroquine diphosphate, the standard reference drug which had a % suppression of 90.36 ± 0.04 (p < 0.05). The in vitro antiplasmodial study indicated that the aqueous extract of the stem bark of C. tabularis displayed good activity against Plasmodium falciparum chloroquine-sensitive (D6) strain (IC50 of 10.739 μg/mL) and chloroquine-resistant (W2) strain. Chloroquine and artemisinin had <0.163 and <0.0264, respectively. PMID:26911147

  9. The sensitivity and selectivity properties of a fluorescence sensor based on quinoline-Bodipy

    Energy Technology Data Exchange (ETDEWEB)

    Nuri Kursunlu, Ahmed, E-mail: ankursunlu@gmail.com; Guler, Ersin

    2014-01-15

    A novel florescence sensor (Q-BODIPY) based on quinoline-Bodipy (quinoline-boradiazaindacene) was prepared by ‘click chemistry’ in several stages. The sensing actions of Q-BODIPY were confirmed by UV–vis titration, emission and excitation spectroscopic studies in presence of Mn{sup 2+}, Co{sup 2+}, Ni{sup 2+}, Cu{sup 2+}, Zn{sup 2+}, Cd{sup 2+}, Sn{sup 2+}, Hg{sup 2+}, Pb{sup 2+}, La{sup 3+}, Ga{sup 3+}, Er{sup 3+} and Yb{sup 3+} ions in methanol:H{sub 2}O (1:1) medium. Whereas some metal ions can only cause quenching effect on the fluorescence intensity of Q-BODIPY, some of them show an increase in fluorescence intensity. The stoichiometry of host–guest complexes formed was determined by Job′s plot method. The binding constants were calculated by Stern–Volmer method. As a fluorescence sensor, Q-BODIPY shows the best selectivity performance against Zn{sup 2+} ions in according to all spectroscopic data. -- Highlights: • Q-BODIPY prepared by several techniques shows a fluorescent behavior toward p, d and f block metal ions. • Q-BODIPY has both a more sensitivity and more effective ability for the detection of Zn(II) ion. • The synthesis strategies to produce Bodipy′s with metal coordinating offer a new approach for the design of novel fluorescence sensors.

  10. The quality of antimalarials available in Yemen

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    Atta Hoda

    2005-06-01

    Full Text Available Abstract Background Malaria has always been a major public health problem in Yemen. Several studies in developing countries have demonstrated ineffective and poor quality drugs including antimalarials. Therefore, quality assessment of antimalarial drugs is of crucial importance. This study aimed to assess the quality of antimalarials (chloroquine and sulfadoxine/pyrimethamine available in Yemen and to determine whether the quality of these products was related to the level of the distribution chain at which the samples were collected or related to the manufacturers. Methods Four samples from each antimalarial product were collected from each of the various levels of the distribution chain. One sample was kept with the research team. Two were tested at Sana'a and Aden Drug Quality Control Laboratories. The fourth was sent to the Centre for Quality Assurance of Medicines in Potchefstroom, South Africa, for analysis. Quality indicators measured were the content of the active ingredient and dissolution rate (for tablets only in comparison to standard specifications for these products in the relevant pharmacopoeia. Results The results identified several problems of sub-standard products within the drug distribution chain. They included high and low failures in ingredient content for chloroquine tablets and chloroquine syrup. There was some dissolution failure for chloroquine tablets, and high sulfadoxine/pyrimethamine tablets dissolution failures. Failures with the dissolution of the pyrimethamine were found at most of the collection points. No clear relationship neither between the quality products and the level of the distribution chain, nor between locally manufactured and imported products was observed. Conclusion There are sub-standard antimalarial products circulating within the drug distribution chains in the country, which will have serious implications on the reduced therapeutic effectiveness and on the development of drug resistance. This

  11. Thermodynamics of organic mixtures containing amines. VIII. Systems with quinoline

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez, Juan Antonio [G.E.T.E.F., Grupo Especializado en Termodinamica de Equilibrio entre Fases, Departamento de Fisica Aplicada, Facultad de Ciencias, Universidad de Valladolid, E-47071 Valladolid (Spain)], E-mail: jagl@termo.uva.es; Domanska, Urszula; Zawadzki, Maciej [Physical Chemistry Division, Faculty of Chemistry, Warsaw University of Technology, 00-664 Warsaw (Poland)

    2008-08-15

    (Solid + liquid) equilibrium temperatures for mixtures containing quinoline and 1-dodecanol, 1-hexadecanol, or 1-octadecanol have been measured using a dynamic method. (Quinoline + benzene, +alkane, or +1-alkanol) systems were investigated using DISQUAC. The corresponding interaction parameters are reported. The model yields a good representation of molar excess Gibbs free energies, G{sup E}, molar excess enthalpies, H{sup E}, and of the (solid + liquid) equilibria, SLE. Interactional and structural effects were analysed comparing H{sup E} and the molar excess internal energy at constant volume, U{sub V}{sup E}. It was encountered that structural effects are very important in systems involving alkanes or 1-alkanols. Interactions between amine molecules are stronger in mixtures with quinoline than in those containing pyridine, which was ascribed to the higher polarizability of quinoline.

  12. Anti-malarial activities of Andrographis paniculata and Hedyotis corymbosa extracts and their combination with curcumin

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    Swain Bijay K

    2009-02-01

    Full Text Available Abstract Background Herbal extracts of Andrographis paniculata (AP and Hedyotis corymbosa (HC are known as hepato-protective and fever-reducing drugs since ancient time and they have been used regularly by the people in the south Asian sub-continent. Methanolic extracts of these two plants were tested in vitro on choloroquine sensitive (MRC-pf-20 and resistant (MRC-pf-303 strains of Plasmodium falciparum for their anti-malarial activity. Methods Growth inhibition was determined using different concentrations of these plant extracts on synchronized P. falciparum cultures at the ring stage. The interactions between these two plant extracts and individually with curcumin were studied in vitro. The performance of these two herbal extracts in isolation and combination were further evaluated in vivo on Balb/c mice infected with Plasmodium berghei ANKA and their efficacy was compared with that of curcumin. The in vivo toxicity of the plant derived compounds as well as their parasite stage-specificity was studied. Results The 50% inhibitory concentration (IC50 of AP (7.2 μg/ml was found better than HC (10.8 μg/ml. Combination of these two herbal drugs showed substantial enhancement in their anti-malarial activity. Combinatorial effect of each of these with curcumin also revealed anti-malarial effect. Additive interaction between the plant extracts (AP + HC and their individual synergism with curcumin (AP+CUR, HC+CUR were evident from this study. Increased in vivo potency was also observed with the combination of plant extracts over the individual extracts and curcumin. Both the plant extracts were found to inhibit the ring stage of the parasite and did not show any in vivo toxicity, whether used in isolation or in combination. Conclusion Both these two plant extracts in combination with curcumin could be an effective, alternative source of herbal anti-malarial drugs.

  13. Influence of LAR and VAR on Para-Aminopyridine Antimalarials Targetting Haematin in Chloroquine-Resistance.

    Science.gov (United States)

    Warhurst, David C; Craig, John C; Raheem, K Saki

    2016-01-01

    Antimalarial chloroquine (CQ) prevents haematin detoxication when CQ-base concentrates in the acidic digestive vacuole through protonation of its p-aminopyridine (pAP) basic aromatic nitrogen and sidechain diethyl-N. CQ export through the variant vacuolar membrane export channel, PFCRT, causes CQ-resistance in Plasmodium falciparum but 3-methyl CQ (sontochin SC), des-ethyl amodiaquine (DAQ) and bis 4-aminoquinoline piperaquine (PQ) are still active. This is determined by changes in drug accumulation ratios in parasite lipid (LAR) and in vacuolar water (VAR). Higher LAR may facilitate drug binding to and blocking PFCRT and also aid haematin in lipid to bind drug. LAR for CQ is only 8.3; VAR is 143,482. More hydrophobic SC has LAR 143; VAR remains 68,523. Similarly DAQ with a phenol substituent has LAR of 40.8, with VAR 89,366. In PQ, basicity of each pAP is reduced by distal piperazine N, allowing very high LAR of 973,492, retaining VAR of 104,378. In another bis quinoline, dichlorquinazine (DCQ), also active but clinically unsatisfactory, each pAP retains basicity, being insulated by a 2-carbon chain from a proximal nitrogen of the single linking piperazine. While LAR of 15,488 is still high, the lowest estimate of VAR approaches 4.9 million. DCQ may be expected to be very highly lysosomotropic and therefore potentially hepatotoxic. In 11 pAP antimalarials a quadratic relationship between logLAR and logResistance Index (RI) was confirmed, while log (LAR/VAR) vs logRI for 12 was linear. Both might be used to predict the utility of structural modifications. PMID:27483471

  14. Expanding the Antimalarial Drug Arsenal—Now, But How?

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    Rajeev K. Mehlotra

    2011-04-01

    Full Text Available The number of available and effective antimalarial drugs is quickly dwindling. This is mainly because a number of drug resistance-associated mutations in malaria parasite genes, such as crt, mdr1, dhfr/dhps, and others, have led to widespread resistance to all known classes of antimalarial compounds. Unfortunately, malaria parasites have started to exhibit some level of resistance in Southeast Asia even to the most recently introduced class of drugs, artemisinins. While there is much need, the antimalarial drug development pipeline remains woefully thin, with little chemical diversity, and there is currently no alternative to the precious artemisinins. It is difficult to predict where the next generation of antimalarial drugs will come from; however, there are six major approaches: (i re-optimizing the use of existing antimalarials by either replacement/rotation or combination approach; (ii repurposing drugs that are currently used to treat other infections or diseases; (iii chemically modifying existing antimalarial compounds; (iv exploring natural sources; (v large-scale screening of diverse chemical libraries; and (vi through parasite genome-based (“targeted” discoveries. When any newly discovered effective antimalarial treatment is used by the populus, we must maintain constant vigilance for both parasite-specific and human-related factors that are likely to hamper its success. This article is neither comprehensive nor conclusive. Our purpose is to provide an overview of antimalarial drug resistance, associated parasite genetic factors (1. Introduction; 2. Emergence of artemisinin resistance in P. falciparum, and the antimalarial drug development pipeline (3. Overview of the global pipeline of antimalarial drugs, and highlight some examples of the aforementioned approaches to future antimalarial treatment. These approaches can be categorized into “short term” (4. Feasible options for now and “long term” (5. Next generation of

  15. In Silico Mining for Antimalarial Structure-Activity Knowledge and Discovery of Novel Antimalarial Curcuminoids

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    Birgit Viira

    2016-06-01

    Full Text Available Malaria is a parasitic tropical disease that kills around 600,000 patients every year. The emergence of resistant Plasmodium falciparum parasites to artemisinin-based combination therapies (ACTs represents a significant public health threat, indicating the urgent need for new effective compounds to reverse ACT resistance and cure the disease. For this, extensive curation and homogenization of experimental anti-Plasmodium screening data from both in-house and ChEMBL sources were conducted. As a result, a coherent strategy was established that allowed compiling coherent training sets that associate compound structures to the respective antimalarial activity measurements. Seventeen of these training sets led to the successful generation of classification models discriminating whether a compound has a significant probability to be active under the specific conditions of the antimalarial test associated with each set. These models were used in consensus prediction of the most likely active from a series of curcuminoids available in-house. Positive predictions together with a few predicted as inactive were then submitted to experimental in vitro antimalarial testing. A large majority from predicted compounds showed antimalarial activity, but not those predicted as inactive, thus experimentally validating the in silico screening approach. The herein proposed consensus machine learning approach showed its potential to reduce the cost and duration of antimalarial drug discovery.

  16. In Silico Mining for Antimalarial Structure-Activity Knowledge and Discovery of Novel Antimalarial Curcuminoids.

    Science.gov (United States)

    Viira, Birgit; Gendron, Thibault; Lanfranchi, Don Antoine; Cojean, Sandrine; Horvath, Dragos; Marcou, Gilles; Varnek, Alexandre; Maes, Louis; Maran, Uko; Loiseau, Philippe M; Davioud-Charvet, Elisabeth

    2016-06-29

    Malaria is a parasitic tropical disease that kills around 600,000 patients every year. The emergence of resistant Plasmodium falciparum parasites to artemisinin-based combination therapies (ACTs) represents a significant public health threat, indicating the urgent need for new effective compounds to reverse ACT resistance and cure the disease. For this, extensive curation and homogenization of experimental anti-Plasmodium screening data from both in-house and ChEMBL sources were conducted. As a result, a coherent strategy was established that allowed compiling coherent training sets that associate compound structures to the respective antimalarial activity measurements. Seventeen of these training sets led to the successful generation of classification models discriminating whether a compound has a significant probability to be active under the specific conditions of the antimalarial test associated with each set. These models were used in consensus prediction of the most likely active from a series of curcuminoids available in-house. Positive predictions together with a few predicted as inactive were then submitted to experimental in vitro antimalarial testing. A large majority from predicted compounds showed antimalarial activity, but not those predicted as inactive, thus experimentally validating the in silico screening approach. The herein proposed consensus machine learning approach showed its potential to reduce the cost and duration of antimalarial drug discovery.

  17. Identification of β-hematin inhibitors in a high-throughput screening effort reveals scaffolds with in vitro antimalarial activity

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    Rebecca D. Sandlin

    2014-12-01

    Full Text Available The emergence of drug resistant strains of Plasmodium spp. creates a critical need for the development of novel antimalarials. Formation of hemozoin, a crystalline heme detoxification process vital to parasite survival serves as an important drug target. The quinoline antimalarials including chloroquine and amodiaquine owe their antimalarial activity to inhibition of hemozoin formation. Though in vivo formation of hemozoin occurs within the presence of neutral lipids, the lipophilic detergent NP-40 was previously shown to serve as a surrogate in the β-hematin (synthetic hemozoin formation process. Consequently, an NP-40 mediated β-hematin formation assay was developed for use in high-throughput screening. Here, the assay was utilized to screen 144,330 compounds for the identification of inhibitors of crystallization, resulting in 530 hits. To establish the effectiveness of these target-based β-hematin inhibitors against Plasmodium falciparum, each hit was further tested in cultures of parasitized red blood cells. This effort revealed that 171 of the β-hematin inhibitors are also active against the parasite. Dose–response data identified 73 of these β-hematin inhibitors have IC50 values ⩽5 μM, including 25 compounds with nanomolar activity against P. falciparum. A scaffold-based analysis of this data identified 14 primary scaffolds that represent 46% of the 530 total hits. Representative compounds from each of the classes were further assessed for hemozoin inhibitory activity in P. falciparum infected human erythrocytes. Each of the hit compounds tested were found to be positive inhibitors, while a negative control did not perturb this biological pathway in culture.

  18. Evaluation of antimalarial, free-radical-scavenging and insecticidal activities of Artemisia scoparia and A. Spicigera, Asteraceae

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    Fariba H. Afshar

    2011-12-01

    Full Text Available Artemisia species (Asteraceae, widespread throughout the world, are a group of important medicinal plants. The extracts of two medicinal plants of this genus, Artemisia scoparia Waldst. & Kit. and A. spicigera C. Koch, were evaluated for potential antimalarial, free-radical-scavenging and insecticidal properties, using the heme biocrystallisation and inhibition assay, the DPPH assay and the contact toxicity bioassay using the pest Tribolium castaneum, respectively. The methanol extracts of both species showed strong free-radical-scavenging activity and the RC50 values were 0.0317 and 0.0458 mg/mL, respectively, for A. scoparia and A. spicigera. The dichloromethane extracts of both species displayed a moderate level of potential antimalarial activity providing IC50 at 0.778 and 0.999 mg/mL for A. scoparia and A. spicigera, respectively. Both species of Artemisia showed insecticidal properties. However, A. spicigera was more effective than A. scoparia.

  19. Andrographolide: A Novel Antimalarial Diterpene Lactone Compound from Andrographis paniculata and Its Interaction with Curcumin and Artesunate

    Science.gov (United States)

    Mishra, Kirti; Dash, Aditya P.; Dey, Nrisingha

    2011-01-01

    Andrographolide (AND), the diterpene lactone compound, was purified by HPLC from the methanolic fraction of the plant Andrographis paniculata. The compound was found to have potent antiplasmodial activity when tested in isolation and in combination with curcumin and artesunate against the erythrocytic stages of Plasmodium falciparum in vitro and Plasmodium berghei ANKA in vivo. IC50s for artesunate (AS), andrographolide (AND), and curcumin (CUR) were found to be 0.05, 9.1 and 17.4 μM, respectively. The compound (AND) was found synergistic with curcumin (CUR) and addictively interactive with artesunate (AS). In vivo, andrographolide-curcumin exhibited better antimalarial activity, not only by reducing parasitemia (29%), compared to the control (81%), but also by extending the life span by 2-3 folds. Being nontoxic to the in vivo system this agent can be used as template molecule for designing new derivatives with improved antimalarial properties. PMID:21760808

  20. Andrographolide: A Novel Antimalarial Diterpene Lactone Compound from Andrographis paniculata and Its Interaction with Curcumin and Artesunate

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    Kirti Mishra

    2011-01-01

    Full Text Available Andrographolide (AND, the diterpene lactone compound, was purified by HPLC from the methanolic fraction of the plant Andrographis paniculata. The compound was found to have potent antiplasmodial activity when tested in isolation and in combination with curcumin and artesunate against the erythrocytic stages of Plasmodium falciparum in vitro and Plasmodium berghei ANKA in vivo. IC50s for artesunate (AS, andrographolide (AND, and curcumin (CUR were found to be 0.05, 9.1 and 17.4 μM, respectively. The compound (AND was found synergistic with curcumin (CUR and addictively interactive with artesunate (AS. In vivo, andrographolide-curcumin exhibited better antimalarial activity, not only by reducing parasitemia (29%, compared to the control (81%, but also by extending the life span by 2-3 folds. Being nontoxic to the in vivo system this agent can be used as template molecule for designing new derivatives with improved antimalarial properties.

  1. [Historical overview of antimalarials used in Venezuela].

    Science.gov (United States)

    Zerpa de Artiles, N

    1993-06-01

    A historical review of antimalarials used in Venezuela is presented from the time when the bark of quina was used until the massive distribution of quinine and metoquine by the Dirección de Malariología y Saneamiento Ambiental. The utility of chloroquine and primaquine against sensible parasite isolates and of sulfadoxine-pyrimethamine and quinine, currently used against P. falciparum resistant strains, is thoroughly discussed. The author suggests use of artemisimine and its derivatives as a very promising antimalarial drug. She also stresses the possibility of the application of new antimalaria vaccine against P. falciparum blood states, presently assayed in the country as an additional tool in malaria control programs. PMID:11640680

  2. Pricing, distribution, and use of antimalarial drugs.

    Science.gov (United States)

    Foster, S D

    1991-01-01

    Prices of new antimalarial drugs are targeted at the "travellers' market" in developed countries, which makes them unaffordable in malaria-endemic countries where the per capita annual drug expenditures are US$ 5 or less. Antimalarials are distributed through a variety of channels in both public and private sectors, the official malaria control programmes accounting for 25-30% of chloroquine distribution. The unofficial drug sellers in markets, streets, and village shops account for as much as half of antimalarials distributed in many developing countries. Use of antimalarials through the health services is often poor; drug shortages are common and overprescription and overuse of injections are significant problems. Anxiety over drug costs may prevent patients from getting the necessary treatment for malaria, especially because of the seasonal appearance of this disease when people's cash reserves are very low. The high costs may lead them to unofficial sources, which will sell a single tablet instead of a complete course of treatment, and subsequently to increased, often irrational demand for more drugs and more injections. Increasingly people are resorting to self-medication for malaria, which may cause delays in seeking proper treatment in cases of failure, especially in areas where chloroquine resistance has increased rapidly. Self-medication is now widespread, and measures to restrict the illicit sale of drugs have been unsuccessful. The "unofficial" channels thus represent an unacknowledged extension of the health services in many countries; suggestions are advanced to encourage better self-medication by increasing the knowledge base among the population at large (mothers, schoolchildren, market sellers, and shopkeepers), with an emphasis on correct dosing and on the importance of seeking further treatment without delay, if necessary. PMID:1893512

  3. Antimalarial activity of some Colombian medicinal plants

    OpenAIRE

    Garavito, G. (G.); Rincon, J.; Arteaga, L.; Hata, Y; Bourdy, Geneviève; Gimenez, A.; Pinzon, R.; Deharo, Eric

    2006-01-01

    Antimalarial activity of 10 vegetal extracts (9 ethanolic extracts and 1 crude alkaloid extract), obtained from eight species traditionally used in Colombia to treat malaria symptoms, was evaluated in culture using Plasmodium falciparum chloroquine resistant (FcB2) strain and in vivo on rodent malaria Plasmodium berghei. The activity on ferriprotoporphyrin biomineralization inhibition test (FBIT) was also assessed. Against Plasmodium falciparum, eight extracts displayed good activity Abuta gr...

  4. Potential antimalarial activity of indole alkaloids

    OpenAIRE

    Frederich, Michel; Tits, Monique; Angenot, Luc

    2008-01-01

    New antimalarial treatments are now urgently required, following the emergence of resistance to the most used drugs. Natural products contribute greatly to the therapeutic arsenal in this area, including artemisinin and quinine (and atovaquone, semi-synthetic). Among the natural products, indole alkaloids represent an interesting class of compounds. Screening carried out to date has revealed several substances active in vitro under the micromolar range and with a good selectivity index. This ...

  5. Antimalarial drug resistance and combination chemotherapy.

    OpenAIRE

    White, N.

    1999-01-01

    Antimarial drug resistance develops when spontaneously occurring parasite mutants with reduced susceptibility are selected, and are then transmitted. Drugs for which a single point mutation confers a marked reduction in susceptibility are particularly vulnerable. Low clearance and a shallow concentration-effect relationship increase the chance of selection. Use of combinations of antimalarials that do not share the same resistance mechanisms will reduce the chance of selection because the cha...

  6. Quinolinic Acid: Neurotoxin or Oxidative Stress Modulator?

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    Lenka Kubicova

    2013-10-01

    Full Text Available Quinolinic acid (2,3-pyridinedicarboxylic acid, QUIN is a well-known neurotoxin. Consequently, QUIN could produce reactive oxygen species (ROS. ROS are generated in reactions catalyzed by transition metals, especially iron (Fe. QUIN can form coordination complexes with iron. A combination of differential pulse voltammetry, deoxyribose degradation and Fe(II autoxidation assays was used for explorating ROS formation in redox reactions that are catalyzed by iron in QUIN-Fe complexes. Differential pulse voltammetry showed an anodic shift of the iron redox potential if iron was liganded by QUIN. In the H2O2/FeCl3/ascorbic acid variant of the deoxyribose degradation assay, the dose-response curve was U-shaped. In the FeCl3/ascorbic acid variant, QUIN unambiguously showed antioxidant effects. In the Fe(II autoxidation assay, QUIN decreased the rate of ROS production caused by Fe(II oxidation. Our study confirms that QUIN toxicity may be caused by ROS generation via the Fenton reaction. This, however, applies only for unnaturally high concentrations that were used in attempts to provide support for the neurotoxic effect. In lower concentrations, we show that by liganding iron, QUIN affects the Fe(II/Fe(III ratios that are beneficial to homeostasis. Our results support the notion that redox chemistry can contribute to explaining the hormetic dose-response effects.

  7. Antimalarial plants of northeast India: An overview

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    Rama Shankar

    2012-01-01

    Full Text Available The need for an alternative drug for malaria initiated intensive efforts for developing new antimalarials from indigenous plants. The information from different tribal communities of northeast India along with research papers, including books, journals and documents of different universities and institutes of northeast India was collected for information on botanical therapies and plant species used for malaria. Sixty-eight plant species belonging to 33 families are used by the people of northeast India for the treatment of malaria. Six plant species, namely, Alstonia scholaris, Coptis teeta, Crotolaria occulta, Ocimum sanctum, Polygala persicariaefolia, Vitex peduncularis, have been reported by more than one worker from different parts of northeast India. The species reported to be used for the treatment of malaria were either found around the vicinity of their habitation or in the forest area of northeast India. The most frequently used plant parts were leaves (33%, roots (31%, and bark and whole plant (12%. The present study has compiled and enlisted the antimalarial plants of northeast India, which would help future workers to find out the suitable antimalarial plants by thorough study.

  8. Anti-malarial activities of Andrographis paniculata and Hedyotis corymbosa extracts and their combination with curcumin

    OpenAIRE

    Swain Bijay K; Dash Aditya P; Mishra Kirti; Dey Nrisingha

    2009-01-01

    Abstract Background Herbal extracts of Andrographis paniculata (AP) and Hedyotis corymbosa (HC) are known as hepato-protective and fever-reducing drugs since ancient time and they have been used regularly by the people in the south Asian sub-continent. Methanolic extracts of these two plants were tested in vitro on choloroquine sensitive (MRC-pf-20) and resistant (MRC-pf-303) strains of Plasmodium falciparum for their anti-malarial activity. Methods Growth inhibition was determined using diff...

  9. A novel way to grow hemozoin-like crystals in vitro and its use to screen for hemozoin inhibiting antimalarial compounds.

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    Vincent Thomas

    Full Text Available BACKGROUND: Hemozoin crystals are normally formed in vivo by Plasmodium parasites to detoxify free heme released after hemoglobin digestion during its intraerythrocytic stage. Inhibition of hemozoin formation by various drugs results in free heme concentration toxic for the parasites. As a consequence, in vitro assays have been developed to screen and select candidate antimalarial drugs based on their capacity to inhibit hemozoin formation. In this report we describe new ways to form hemozoin-like crystals that were incidentally discovered during research in the field of prion inactivation. METHODS: We investigated the use of a new assay based on naturally occurring "self-replicating" particles and previously described as presenting resistance to decontamination comparable to prions. The nature of these particles was determined using electron microscopy, Maldi-Tof analysis and X-ray diffraction. They were compared to synthetic hemozoin and to hemozoin obtained from Plasmodium falciparum. We then used the assay to evaluate the capacity of various antimalarial and anti-prion compounds to inhibit "self-replication" (crystallisation of these particles. RESULTS: We identified these particles as being similar to ferriprotoporphyrin IX crystal and confirmed the ability of these particles to serve as nuclei for growth of new hemozoin-like crystals (HLC. HLC are morphologically similar to natural and synthetic hemozoin. Growth of HLC in a simple assay format confirmed inhibition by quinolines antimalarials at potencies described in the literature. Interestingly, artemisinins and tetracyclines also seemed to inhibit HLC growth. CONCLUSIONS: The described HLC assay is simple and easy to perform and may have the potential to be used as an additional tool to screen antimalarial drugs for their hemozoin inhibiting activity. As already described by others, drugs that inhibit hemozoin crystal formation have also the potential to inhibit misfolded proteins

  10. The thermodynamic properties of quinoline and isoquinoline: Topical report

    Energy Technology Data Exchange (ETDEWEB)

    Steele, W.V.; Archer, D.G.; Chirico, R.D.; Collier, W.B.; Gammon, B.E.; Hossenloop, I.A.; Nguyen, A.; Smith, N.K.

    1988-03-01

    Measurements leading to the calculation of the ideal-gas thermodynamic properties for quinoline and isoquinoline are reported. Thermodynamic and thermophysical properties were determined by adiabatic heat-capacity calorimetry, comparative ebulliometry, densimetry, and combustion calorimetry. Vibrational spectra of quinoline and isoquinoline were assigned. Entropies and enthalpies for the ideal-gas state from the claorimetric measurements and from the vibrational assignments were derived and compared. Entropies, enthalpies, and Gibbs energies of formation were derived at selected temperatues between T..-->..0 and 1000 K. new density measurements for benzene are reported. 55 refs., 11 figs., 16 tabs.

  11. Bioremediation of Quinoline-contaminated Soil Using Bioaugmentation in Slurry-phase Reactor

    Institute of Scientific and Technical Information of China (English)

    JIAN-LONG WANG; ZE-YU MAO; LI-PING HAN; YI QIAN

    2004-01-01

    Objective To investigate the possibility of using bioaugmentation as a strategy for remediating quinoline-contaminated soil. Methods Microorganisms were introduced to the soil to assess the feasibility of enhancing the removal of quinoline from quinoline-contaminated soil. Slurry-phase reactor was used to investigate the bioremediation of quinoline-contaminated soil. HPLC (Hewlett-Packard model 5050 with an UV detector) was used for analysis of quinoline concentration. Results The biodegradation rate of quinoline was increased through the introduction of Burkholderia pickettii. Quinoline, at a concentration of 1 mg/g soil, could be removed completely within 6 and 8 hours with and without combined effect of indigenous microbes, respectively. Although the indigenous microbes alone had no quinoline-degrading ability, they cooperated with the introduced quinoline-degrader to remove quinoline more quickly than the introduced microbes alone. Bioaugmentaion process was accelerated by the increase of inoculum size and bio-stimulation. The ratio of water to soil in slurry had no significant impact on bioremediation results. Conclusion Bioaugmetation is an effective way for bioremediation of quinoline-contaminated soil.

  12. Anticancer properties of distinct antimalarial drug classes.

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    Rob Hooft van Huijsduijnen

    Full Text Available We have tested five distinct classes of established and experimental antimalarial drugs for their anticancer potential, using a panel of 91 human cancer lines. Three classes of drugs: artemisinins, synthetic peroxides and DHFR (dihydrofolate reductase inhibitors effected potent inhibition of proliferation with IC50s in the nM- low µM range, whereas a DHODH (dihydroorotate dehydrogenase and a putative kinase inhibitor displayed no activity. Furthermore, significant synergies were identified with erlotinib, imatinib, cisplatin, dasatinib and vincristine. Cluster analysis of the antimalarials based on their differential inhibition of the various cancer lines clearly segregated the synthetic peroxides OZ277 and OZ439 from the artemisinin cluster that included artesunate, dihydroartemisinin and artemisone, and from the DHFR inhibitors pyrimethamine and P218 (a parasite DHFR inhibitor, emphasizing their shared mode of action. In order to further understand the basis of the selectivity of these compounds against different cancers, microarray-based gene expression data for 85 of the used cell lines were generated. For each compound, distinct sets of genes were identified whose expression significantly correlated with compound sensitivity. Several of the antimalarials tested in this study have well-established and excellent safety profiles with a plasma exposure, when conservatively used in malaria, that is well above the IC50s that we identified in this study. Given their unique mode of action and potential for unique synergies with established anticancer drugs, our results provide a strong basis to further explore the potential application of these compounds in cancer in pre-clinical or and clinical settings.

  13. Artemisinins: pharmacological actions beyond anti-malarial.

    Science.gov (United States)

    Ho, Wanxing Eugene; Peh, Hong Yong; Chan, Tze Khee; Wong, W S Fred

    2014-04-01

    Artemisinins are a family of sesquiterpene trioxane lactone anti-malarial agents originally derived from Artemisia annua L. The anti-malarial action of artemisinins involves the formation of free radicals via cleavage of the endoperoxide bond in its structure, which mediate eradication of the Plasmodium species. With its established safety record in millions of malarial patients, artemisinins are also being investigated in diseases like infections, cancers and inflammation. Artemisinins have been reported to possess robust inhibitory effects against viruses (e.g. Human cytomegalovirus), protozoa (e.g. Toxoplasma gondii), helminths (e.g. Schistosoma species and Fasciola hepatica) and fungi (e.g. Cryptococcus neoformans). Artemisinins have demonstrated cytotoxic effects against a variety of cancer cells by inducing cell cycle arrest, promoting apoptosis, preventing angiogenesis, and abrogating cancer invasion and metastasis. Artemisinins have been evaluated in animal models of autoimmune diseases, allergic disorders and septic inflammation. The anti-inflammatory effects of artemisinins have been attributed to the inhibition of Toll-like receptors, Syk tyrosine kinase, phospholipase Cγ, PI3K/Akt, MAPK, STAT-1/3/5, NF-κB, Sp1 and Nrf2/ARE signaling pathways. This review provides a comprehensive update on non-malarial use of artemisinins, modes of action of artemisinins in different disease conditions, and drug development of artemisinins beyond anti-malarial. With the concerted efforts in the novel synthesis of artemisinin analogs and clinical pharmacology of artemisinins, it is likely that artemisinin drugs will become a major armamentarium combating a variety of human diseases beyond malaria. PMID:24316259

  14. Antimalarial Activity of Ultra-Short Peptides

    Directory of Open Access Journals (Sweden)

    María Yolanda Rios

    2009-12-01

    Full Text Available Ultra-short peptides 1-9 were designed and synthesized with phenylalanine, ornithine and proline amino acid residues and their effect on antimalarial activity was analyzed. On the basis of the IC50 data for these compounds, the effects of nature, polarity, and amino acid sequence on Plasmodium berghei schizont cultures were analyzed too. Tetrapeptides Phe-Orn-Phe-Orn (4 and Lys-Phe-Phe-Orn (5 showed a very important activity with IC50 values of 3.31 and 2.57 μM, respectively. These two tetrapeptides are candidates for subsequent in vivo assays and SARS investigations.

  15. Dasycarine, a New Quinoline Alkaloid from Dictamnus dasycarpus

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Dasycarine, a new quinoline alkaloid along with five known compounds, dictamine, dihydroobacunone, obacunone, fraxinellone and b -sitosterol, were isolated from Dictamnus dasycarpus. The structure of dasycarine was identified as 4, 5, 8- trimethoxyl -3- (3- methyl -2- butenyl)- 2- quinone by 1D and 2D NMR techniques.

  16. UV action spectroscopy of protonated PAH derivatives. Methyl substituted quinolines

    DEFF Research Database (Denmark)

    Klærke, Benedikte; Holm, Anne; Andersen, Lars Henrik

    2011-01-01

    Aims. We investigate the production of molecular photofragments upon UV excitation of PAH derivatives, relevant for the interstellar medium. Methods. The action absorption spectra of protonated gas-phase methyl-substituted quinolines (CH3−C9H7NH+) have been recorded in the 215–338 nm spectral range...

  17. Transformation of indole and quinoline by Desulfobacterium indolicum (DSM 3383)

    DEFF Research Database (Denmark)

    Licht, D.; Johansen, S.S.; Arvin, E.;

    1996-01-01

    kinetics. The kinetic parameters for indole were an apparent maximum specific transformation rate (V-Amax) of 263 mu mol mg total protein(-1) day(-1) and an apparent half-saturation constant (K-Am) of 139 mu M. The V-Amax for quinoline was 170 mu mol mg total protein(-1) day(-1) and K-Am was 92 mu M...

  18. An efficient synthesis of quinolines under solvent-free conditions

    Indian Academy of Sciences (India)

    Mihir K Chaudhuri; Sahid Hussain

    2006-03-01

    An efficient synthesis of substituted quinolines has been achieved in a one-pot reaction from -nitrobenzaldehyde and enolizable ketones using SnCl2.2H2O as the reductant under microwave irradiation without any solvent or catalyst.

  19. Malaria and antimalarial plants in Roraima, Brazil.

    Science.gov (United States)

    Milliken, W

    1997-01-01

    One of the numerous problems created by the gold rush which took place in northern Brazil (Roraima State) at the end of the 1980s was a severe epidemic of malaria amongst the indigenous peoples of the region. Worst hit were the Yanomami Indians, who had lived in almost total isolation prior to this event. The problem has been exacerbated by the development of chloroquine-resistant strains of Plasmodium falciparum. In an effort to identify viable alternatives to dependence on western medicine for malaria treatment, a survey was carried out on the local plant species (wild and cultivated) used for this purpose in Roraima. Fieldwork was carried out amongst seven indigenous peoples, as well as with the non-indigenous settlers. Over 90 species were collected, many of which have been cited as used for treatment of malaria and fevers elsewhere. Knowledge of antimalarial plants was found to vary greatly between the communities, and in some cases there was evidence of recent experimentation. Initial screening of plant extracts has shown a high incidence of significant antimalarial activity amongst the species collected. PMID:9204719

  20. Chitosan-based nanocarriers for antimalarials

    Science.gov (United States)

    Dreve, Simina; Kacso, Iren; Popa, Adriana; Raita, Oana; Bende, A.; Borodi, Gh.; Bratu, I.

    2012-02-01

    The objective of this research was to synthesize and characterize chitosan-based liquid and solid materials with unique absorptive and mechanical properties as carriers for quinine - one of the most used antimalarial drug. The use of chitosan (CTS) as base in polyelectrolyte complex systems, to prepare solid release systems as sponges is presented. The preparation by double emulsification of CTS hydrogels carrying quinine as anti-malarial drug is reported. The concentration of quinine in the CTS hydrogel was 0.08 mmol. Chitosan - drug loaded hydrogel was used to generate solid sponges by freeze-drying at -610°C and 0.09 atm. Structural investigations of the solid formulations were done by Fourier-transformed infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-VIS), spectrofluorimetry, differential scanning calorimetry (DSC) and X-ray diffractometry. The results indicated that the drug molecule is forming temporary chelates in CTS hydrogels and sponges. Electron paramagnetic resonance (EPR) demonstrates the presence of free radicals in a wide range and the antioxidant activity for chitosan - drug supramolecular cross-linked assemblies.

  1. Methanol Asinger's vision today

    CERN Document Server

    Bertau, Martin; Plass, Ludolf; Schmidt, Friedrich; Wernicke, Hans-Jürgen

    2014-01-01

    Methanol - The Chemical and Energy Feedstock of the Future offers a visionary yet unbiased view of methanol technology. Based on the groundbreaking 1986 publication ""Methanol"" by Friedrich Asinger, this book includes contributions by more than 40 experts from industry and academia. The authors and editors provide a comprehensive exposition of methanol chemistry and technology which is useful for a wide variety of scientists working in chemistry and energy related industries as well as academic researchers and even decision-makers and organisations concerned with the future of chemical and e

  2. The Methanol Economy Project

    Energy Technology Data Exchange (ETDEWEB)

    Olah, George [Univ. of Southern California, Los Angeles, CA (United States); Prakash, G. K. [Univ. of Southern California, Los Angeles, CA (United States)

    2014-02-01

    The Methanol Economy Project is based on the concept of replacing fossil fuels with methanol generated either from renewable resources or abundant natural (shale) gas. The full methanol cycle was investigated in this project, from production of methanol through bromination of methane, bireforming of methane to syngas, CO2 capture using supported amines, co-electrolysis of CO2 and water to formate and syngas, decomposition of formate to CO2 and H2, and use of formic acid in a direct formic acid fuel cell. Each of these projects achieved milestones and provided new insights into their respective fields.

  3. Synthesis, photochemistry, DNA cleavage/binding and cytotoxic properties of fluorescent quinoxaline and quinoline hydroperoxides.

    Science.gov (United States)

    Chowdhury, Nilanjana; Gangopadhyay, Moumita; Karthik, S; Pradeep Singh, N D; Baidya, Mithu; Ghosh, S K

    2014-01-01

    Novel fluorescent quinoxaline and quinoline hydroperoxides were shown to perform dual role as both fluorophores for cell imaging and photoinduced DNA cleaving agents. Photophysical studies of newly synthesized quinoxaline and quinoline hydroperoxides showed that they all exhibited moderate to good fluorescence. Photolysis of quinoxaline and quinoline hydroperoxides in acetonitrile using UV light above 350nm resulted in the formation of corresponding ester compounds via γ-hydrogen abstraction by excited carbonyl chromophore. Single strand DNA cleavage was achieved on irradiation of newly synthesized hydroperoxides by UV light (⩾350nm). Both hydroxyl radicals and singlet oxygen were identified as reactive oxygen species (ROS) responsible for the DNA cleavage. Further, we showed quinoline hydroperoxide binds to ct-DNA via intercalative mode. In vitro biological studies revealed that quinoline hydroperoxide has good biocompatibility, cellular uptake property and cell imaging ability. Finally, we showed that quinoline hydroperoxide can permeate into cells efficiently and may cause cytotoxicity upon irradiation by UV light.

  4. A combination of the leaves and tuber of Icacina senegalensis A. Juss (Icacinaceae improves the antimalarial activity of the plant in mice

    Directory of Open Access Journals (Sweden)

    Esien David-Oku

    2015-10-01

    Full Text Available Objective: To investigate the possibility of increased antimalarial activity of Icacina senegalensis A. Juss (Icacinaceae upon a combination of its leaves and tubers against Plasmodium berghei malaria in mice. Methods: Chloroquine sensitive ANKA clones of Plasmodium berghei were used to develop experimental models based on intraperitoneal injection of 107 parasitized erythrocytes in phosphate buffer saline (pH 7.2 and subsequent development of parasitemia. The models were employed to investigate prophylactic and curative anti-malarial activities of tuber and tuberleaf methanol extracts of the plant at selected dosages (25, 50 and 100 mg/kg body weight. Chloroquine with a curative dosage of 10 mg/kg body weight was used as positive control in both studies. Results: Tuber and tuber-leaf extracts produced a dose-dependent chemosuppression of the parasites, with higher activity and mean survival time exhibited by the combined extract. Conclusions: Anti-plasmodia activity has been discovered in methanol extract of Icacina senegalensis tuber extract. The observed optimization of the antimalarial actions of the plant upon a combination of its leaf and tuber opens a new area of medicinal plant research.

  5. A combination of the leaves and tuber ofIcacina senegalensis A. Juss (Icacinaceae) improves the antimalarial activity of the plant in mice

    Institute of Scientific and Technical Information of China (English)

    Esien David-Oku; Juliet Ifeoma Obiajunwa-Otteh

    2015-01-01

    Objective:To investigate the possibility of increased antimalarial activity ofIcacina senegalensis A. Juss (Icacinaceae) upon a combination of its leaves and tubers against Plasmodium berghei malaria in mice. Methods: Chloroquine sensitiveANKA clones ofPlasmodium berghei were used to develop experimental models based on intraperitoneal injection of 107 parasitized erythrocytes in phosphate buffer saline (pH 7.2) and subsequent development of parasitemia. The models were employed to investigate prophylactic and curative anti-malarial activities of tuber and tuber-leaf methanol extracts of the plant at selected dosages (25, 50 and 100 mg/kg body weight). Chloroquine with a curative dosage of 10 mg/kg body weight was used as positive control in both studies. Results:Tuber and tuber-leaf extracts produced a dose-dependent chemosuppression of the parasites, with higher activity and mean survival time exhibited by the combined extract. Conclusions:Anti-plasmodia activity has been discovered in methanol extract ofIcacina senegalensis tuber extract. The observed optimization of the antimalarial actions of the plant upon a combination of its leaf and tuber opens a new area of medicinal plant research.

  6. Artemisinin anti-malarial drugs in China.

    Science.gov (United States)

    Guo, Zongru

    2016-03-01

    Discovered by Youyou Tu, one of the 2015 Nobel Prize winners in Physiology or Medicine, together with many other Chinese scientists, artemisinin, artemether and artesunate, as well as other artemisinins, have brought the global anti-malarial treatment to a new era, saving millions of lives all around the world for the past 40 years. The discoveries of artemisinins were carried out beginning from the 1970s, a special period in China, by hundreds of scientists all together under the "whole nation" system. This article focusing on medicinal chemistry research, briefly introduced the discovery and invention course of the scientists according to the published papers, and highlighted their academic contribution and achievements. PMID:27006895

  7. DETECTION OF PUTATIVE ANTIMALARIAL-RESISTANT PLASMODIUM VIVAX IN ANOPHELES VECTORS AT THAILAND-CAMBODIA AND THAILAND-MYANMAR BORDERS.

    Science.gov (United States)

    Rattaprasert, Pongruj; Chaksangchaichot, Panee; Wihokhoen, Benchawan; Suparach, Nutjaree; Sorosjinda-Nunthawarasilp, Prapa

    2016-03-01

    Monitoring of multidrug-resistant (MDR)falciparum and vivax malaria has recently been included in the Global Plan for Artemisinin Resistance Containment (GPARC) of the Greater Mekong Sub-region, particularly at the Thailand-Cambodia and Thailand-Myanmar borders. In parallel to GPARC, monitoring MDR malaria parasites in anopheline vectors is an ideal augment to entomological surveillance. Employing Plasmodium- and species-specific nested PCR techniques, only P. vivax was detected in 3/109 salivary gland DNA extracts of anopheline vectors collected during a rainy season between 24-26 August 2009 and 22-24 September 2009 and a dry season between 29-31 December 2009 and 16-18 January 2010. Indoor and out- door resting mosquitoes were collected in Thong Pha Phum District, Kanchanaburi Province (border of Thailand-Myanmar) and Bo Rai District, Trat Province (border of Thailand-Cambodia): one sample from Anopheles dirus at the Thailand-Cambodia border and two samples from An. aconitus from Thailand-Myanmar border isolate. Nucleotide sequencing of dihydrofolate reductase gene revealed the presence in all three samples of four mutations known to cause high resistance to antifolate pyrimethamine, but no mutations were found in multidrug resistance transporter 1 gene that are associated with (falciparum) resistance to quinoline antimalarials. Such findings indicate the potential usefulness of this approach in monitoring the prevalence of drug-resistant malaria parasites in geographically regions prone to the development of drug resistance and where screening of human population at risk poses logistical and ethical problems. Keywords: Anopheles spp, Plasmodium vivax, antimalarial resistance, Greater Mekong Sub-region, nested PCR, vector surveillance PMID:27244954

  8. Synthesis and evaluation of antimalarial activity of curcumin derivatives

    International Nuclear Information System (INIS)

    ne of the main challenges in the development of new antimalarial drugs is to achieve a viable lead candidate with good pharmacokinetic properties. Curcumin has a broad range of biological activities, including antimalarial activity. Herein, we report the antimalarial activity of six curcumin derivatives (6-12) and an initial analysis of their pharmacokinetic properties. Five compounds have demonstrated potent activity against the P. falciparum in vitro (IC50 values ranging from 1.7 to 15.2 μg mL-1), with moderate or low cytotoxicity against the HeLa cell line. The substitution of the carbonyl group in 6 by a 2,4-dinitrophenylhydrazone group (to afford 11) increases the Selective Index. These preliminary results indicate curcumin derivatives as potential antimalarial compounds. (author)

  9. Drug Discovery and Development of Antimalarial Agents: Recent Advances.

    Science.gov (United States)

    Thota, Sreekanth; Yerra, Rajeshwar

    2016-01-01

    Malaria, a deadly infectious parasitic disease, is a major issue of public health in the world today and already produces serious economic constraints in the endemic countries. Most of the malarial infections and deaths are due to Plasmodium falciparum and Plasmodium vivax species. The recent emergence of resistance necessitates the search for new antimalarial drugs, which overcome the resistance and act through new mechanisms. Although much effort has been directed towards the discovery of novel antimalarial drugs. 4-anilino quinolone triazines as potent antimalarial agents, their in silico modelling and bioevaluation as Plasmodium falciparum transketolase and β-hematin inhibitors has been reported. This review is primarily focused on the drug discovery of the recent advances in the development of antimalarial agents and their mechanism of action.

  10. Pyrolysis mechanisms of quinoline and isoquinoline with density functional theory

    Energy Technology Data Exchange (ETDEWEB)

    Ling, L.X.; Zhang, R.G.; Wang, B.J.; Xie, K.C. [Taiyuan University of Technology, Taiyuan (China)

    2009-10-15

    The pyrolysis mechanisms of quinoline and isoquinoline were investigated using the density functional theory of quantum chemistry, including eight reaction paths and a common tautomeric intermediate 1-indene imine. It is concluded that the conformational tautomerism of the intermediate decides the pyrolysis products (C{sub 6}H{sub 6}, HC C-C N, C6H{sub 5}C N and HC CH) to be the same, and also decides the total disappearance rates of the reactants to be the same, for both original reactants quinoline and isoquinoline during the pyrolysis reaction. The results indicate that the intramolecular hydrogen migration is an important reaction step, which often appears in the paths of the pyrolysis mechanism. The activation energies of the rate determining steps are obtained. The calculated results are in good agreement with the experimental results.

  11. Quinoline-2-thiol Derivatives as Fluorescent Sensors for Metals, pH and HNO

    Directory of Open Access Journals (Sweden)

    Naphtali A. O’Connor

    2014-06-01

    Full Text Available A tautomeric equilibrium exists for quinoline-2-thiol and quinoline-2(1H-thione. Quantum mechanical calculations predict the thione is the major tautomer and this is confirmed by the absorption spectra. The utility of quinolone-2-thiol/quinoline-2(1H-thione as a chromophore for developing fluorescent sensors is explored. No fluorescence is observed when excited at absorption maxima, however a fluorescence increase is observed when exposed to HNO, a molecule of import as a cardiovascular therapeutic. Alkylated quinoline-2-thiol derivatives are found to be fluorescent and show a reduction in fluorescence when exposed to metals and changes in pH.

  12. Mineralization of Quinoline by BDD Anodes: Variable Effects and Its Effluent Characteristics

    OpenAIRE

    Wang, C.R.; Wang, J.; Ma, X. G.; Li, H.; Zhang, S.Z.

    2015-01-01

    BDD anodes were selected for quinoline mineralization and influence of operating parameters, such as current density, initial quinoline concentration, supporting electrolyte, and initial pH was investigated. Based on the consideration of quinoline removal efficiency and average current efficiency, at initial quinoline concentration of 50 mg L−1 and pH of 7, the optimal condition was confirmed as current density of 75 mA cm−2, electrolysis time of 1.5 h, and Na2SO4 concentration of 0.05 mol L−...

  13. Antimalarial activity of plumbagin in vitro and in animal models

    OpenAIRE

    Sumsakul, Wiriyaporn; Plengsuriyakarn, Tullayakorn; Chaijaroenkul, Wanna; Viyanant, Vithoon; Karbwang, Juntra; Na-Bangchang, Kesara

    2014-01-01

    Background Plumbagin is the major active constituent in several plants including Plumbago indica Linn. (root). This compound has been shown to exhibit a wide spectrum of biological and pharmacological activities. The present study aimed to evaluate the in vitro and in vivo antimalarial activity of plumbagin including its acute and subacute toxicity in mice. Methods In vitro antimalarial activity of plumbagin against K1 and 3D7 Plasmodium falciparum clones were assessed using SYBR Green I base...

  14. Towards optimal design of anti-malarial pharmacokinetic studies.

    OpenAIRE

    White Nicholas J; Price Ric N; Jamsen Kris M; Simpson Julie A; Lindegardh Niklas; Tarning Joel; Duffull Stephen B

    2009-01-01

    Abstract Background Characterization of anti-malarial drug concentration profiles is necessary to optimize dosing, and thereby optimize cure rates and reduce both toxicity and the emergence of resistance. Population pharmacokinetic studies determine the drug concentration time profiles in the target patient populations, including children who have limited sampling options. Currently, population pharmacokinetic studies of anti-malarial drugs are designed based on logistical, financial and ethi...

  15. Antimalarial activity of Malaysian Plectranthus amboinicus against Plasmodium berghei

    OpenAIRE

    Ramli, Norazsida; Ahamed, Pakeer Oothuman Syed; Elhady, Hassan Mohamed; Taher, Muhammad

    2014-01-01

    Context: Malaria is a mosquito-borne disease caused by parasitic protozoa from the genus of Plasmodium. The protozoans have developed resistance against many of current drugs. It is urgent to find an alternative source of new antimalarial agent. In the effort to discover new antimalarial agents, this research has been conducted on Plectranthus amboinicus. Aims: This study was conducted to evaluate the toxicity and antiplasmodial properties of P. amboinicus. Materials and Methods: Acute oral t...

  16. Expanding the Antimalarial Drug Arsenal—Now, But How?

    OpenAIRE

    MEHLOTRA, RAJEEV K.; Grimberg, Brian T

    2011-01-01

    The number of available and effective antimalarial drugs is quickly dwindling. This is mainly because a number of drug resistance-associated mutations in malaria parasite genes, such as crt, mdr1, dhfr/dhps, and others, have led to widespread resistance to all known classes of antimalarial compounds. Unfortunately, malaria parasites have started to exhibit some level of resistance in Southeast Asia even to the most recently introduced class of drugs, artemisinins. While there is much need, th...

  17. In Vitro Antimalarial Activity of Novel Semisynthetic Nocathiacin I Antibiotics

    OpenAIRE

    Sharma, Indu; Sullivan, Margery; McCutchan, Thomas F.

    2015-01-01

    Presently, the arsenal of antimalarial drugs is limited and needs to be replenished. We evaluated the potential antimalarial activity of two water-soluble derivatives of nocathiacin (BMS461996 and BMS411886) against the asexual blood stages of Plasmodium falciparum. Nocathiacins are a thiazolyl peptide group of antibiotics, are structurally related to thiostrepton, have potent activity against a wide spectrum of multidrug-resistant Gram-positive bacteria, and inhibit protein synthesis. The in...

  18. Gold-catalyzed oxidative cycloadditions to activate a quinoline framework.

    Science.gov (United States)

    Huple, Deepak B; Ghorpade, Satish; Liu, Rai-Shung

    2013-09-23

    Going for gold! Gold-catalyzed reactions of 3,5- and 3,6-dienynes with 8-alkylquinoline oxides results in an oxidative cycloaddition with high stereospecificity (see scheme; EWG = electron-withdrawing group); this process involves a catalytic activation of a quinoline framework. The reaction mechanism involves the intermediacy of α-carbonyl pyridinium ylides (I) in a concerted [3+2]-cycloaddition with a tethered alkene.

  19. Activities of new quinoline derivatives against genital pathogens.

    OpenAIRE

    AZNAR;, J.; Caballero, M C; Lozano, M C; Miguel, C. de; Palomares, J C; Perea, E J

    1985-01-01

    The in vitro activities of four quinoline carboxylic acids against 48 strains of Neisseria gonorrhoeae, 10 of Chlamydia trachomatis, and 32 of Ureaplasma urealyticum were compared. Ciprofloxacin was the most active against N. gonorrhoeae and C. trachomatis but had poor bactericidal activity against U. urealyticum, whereas ofloxacin showed the most bactericidal activity against U. urealyticum but was less active than ciprofloxacin against the two former pathogens. Norfloxacin and enoxacin were...

  20. How do antimalarial drugs reach their intracellular targets?

    Directory of Open Access Journals (Sweden)

    Katherine eBasore

    2015-05-01

    Full Text Available Drugs represent the primary treatment available for human malaria, as caused by Plasmodium spp. Currently approved drugs and antimalarial drug leads generally work against parasite enzymes or activities within infected erythrocytes. To reach their specific targets, these chemicals must cross at least three membranes beginning with the host cell membrane. Uptake at each membrane may involve partitioning and diffusion through the lipid bilayer or facilitated transport through channels or carriers. Here, we review the features of available antimalarials and examine whether transporters may be required for their uptake. Our computational analysis suggests that most antimalarials have high intrinsic membrane permeability, obviating the need for uptake via transporters; a subset of compounds appear to require facilitated uptake. We also review parasite and host transporters that may contribute to drug uptake. Broad permeability channels at the erythrocyte and parasitophorous vacuolar membranes of infected cells relax permeability constraints on antimalarial drug design; however, this uptake mechanism is prone to acquired resistance as the parasite may alter channel activity to reduce drug uptake. A better understanding of how antimalarial drugs reach their intracellular targets is critical to prioritizing drug leads for antimalarial development and may reveal new targets for therapeutic intervention.

  1. Assessment of Antimalarial Activity against Plasmodium falciparum and Phytochemical Screening of Some Yemeni Medicinal Plants

    Directory of Open Access Journals (Sweden)

    Mohammed A. Alshawsh

    2009-01-01

    Full Text Available Developing countries, where malaria is one of the most prevalent diseases, still rely on traditional medicine as a source for the treatment of this disease. In the present study, six selected plants (Acalypha fruticosa, Azadirachta indica, Cissus rotundifolia, Echium rauwalfii, Dendrosicyos socotrana and Boswellia elongata commonly used in Yemen by traditional healers for the treatment of malaria as well as other diseases, were collected from different localities of Yemen, dried and extracted with methanol and water successfully. The antiplasmodial activity of the extracts was evaluated against fresh clinical isolates of Plasmodium falciparum. The selectivity parameters to evaluate the efficacy of these medicinal plants were measured by in vitro micro test (Mark III according to World Health Organization (WHO 1996 & WHO 2001 protocols of antimalarial drug tests. Among the investigated 12 extracts, three were found to have significant antiplasmodial activity with IC50 values less than 4 µg/ml, namely the water extracts of A. fruticosa, A. indica and D. socotrana. Six extracts showed moderate activity with IC50 values ranging from 10 to 30 µg/ml and three appeared to be inactive with IC50 values more than 30 µg/ml. In addition, preliminary phytochemical screening of the methanolic and aqueous extracts indicated the presence of saponins, tannins, flavonoids, terpenoids, polysaccharides and peptides.

  2. Nꞌ-{[2-(Piperidin-1-yl)quinolin-3-yl]methylene}pyridine-4-carbohydrazide

    OpenAIRE

    Rajiv K. Tonk; Suresh Kumar; Sandhya Bawa; Obaid Afzal

    2012-01-01

    Nꞌ-{[2-(piperidin-1-yl)quinolin-3-yl]methylene}pyridine-4-carbohydrazide 2 has been synthesized through condensation of 2-(piperidin-1-yl)quinoline-3-carbaldehyde 1 with isonicotinic acid hydrazide (INH) in absolute ethanol. The structure of the title compound 2 was established on the basis of IR, 1H-NMR, 13C-NMR and mass spectral data.

  3. Degradation pathway of quinolines in a biofilm system under denitrifying conditions

    Energy Technology Data Exchange (ETDEWEB)

    Johansen, S.S.; Arvin, E.; Mosbaek, H. [Technical Univ. of Denmark, Lyngby (Denmark). Dept. of Environmental Science and Engineering; Hansen, A.B. [National Environmental Research Inst., Roskilde (Denmark). Dept. of Environmental Chemistry

    1997-09-01

    This article reports for the first time the degradation pathways of quinoline, isoquinoline, and methylquinolines by a mixed culture in a biofilm under nitrate-reducing conditions. A simple reverse-phase high-performance liquid chromatography method using ultraviolet detection at 223 nm for determination of seven quinoline analogues and 15 metabolites was developed, and gas chromatography--mass spectrometry and thin-layer chromatography analyses were used for identification. The inhibition of nitrification by the parent compounds and their degradation products was assessed by a nitrification toxicity test called MINNTOX. Quinoline and 3-, 4-, 6-, and 8-methylquinoline were all transformed by hydroxylation into their 2-hydroxyquinoline analogues (2-quinolinones), and isoquinoline was transformed into 1-hydroxyisoquinoline. 2-Methylquinoline was not transformed by this microcosm, likely due to the blockage at position 2 by the methyl group. The hydroxylated metabolites of isoquinoline and quinolines methylated at the heterocyclic ring were not transformed further, whereas metabolites of quinoline and quinolines methylated at the homocyclic ring were hydrogenated at position 3 and 4, and the resulting 3,4-dihydro-2-quinolinone analogues accumulated. Of these metabolites, only 3,4-dihydro-2-quinolinone from the degradation of quinoline was further transformed into unidentified products. All quinolines and their metabolites had inhibiting effects on the nitrifying bacteria at the same level (ppm) in the applied bioassay, indicating that the inhibition of the compounds was not influenced by the initial transformation reactions.

  4. Antimalarial activity of some Colombian medicinal plants.

    Science.gov (United States)

    Garavito, G; Rincón, J; Arteaga, L; Hata, Y; Bourdy, G; Gimenez, A; Pinzón, R; Deharo, E

    2006-10-11

    Antimalarial activity of 10 vegetal extracts (9 ethanolic extracts and 1 crude alkaloid extract), obtained from eight species traditionally used in Colombia to treat malaria symptoms, was evaluated in culture using Plasmodium falciparum chloroquine resistant (FcB2) strain and in vivo on rodent malaria Plasmodium berghei. The activity on ferriprotoporphyrin biomineralization inhibition test (FBIT) was also assessed. Against Plasmodium falciparum, eight extracts displayed good activity Abuta grandifolia (Mart.) Sandwith (Menispermaceae) leaves, Acacia farnesiana (L.) Willd. (Mimosaceae) leaves, Acnistus arborescens (L.) Schltdl. (Solanaceae) aerial part, Croton leptostachyus Kunth (Euphorbiaceae) aerial part, Piper cumanense Kunth (Piperaceae) fruits and leaves, Piper holtonii C. DC. (Piperaceae) aerial part and Xylopia aromatica (Lam.) Mart. (Annonaceae) bark with IC(50) values ranging from <1 to 2.1 microg/ml, while in the in vivo model only Abuta grandifolia alkaloid crude extract exhibits activity, inhibiting 66% of the parasite growth at 250 mg/kg/day. In the FBIT model, five extracts were active (Abuta grandifolia, Croton leptostachyus, Piper cumanense fruit and leaves and Xylopia aromatica). PMID:16713157

  5. A database of antimalarial drug resistance

    Directory of Open Access Journals (Sweden)

    Ringwald Pascal

    2006-06-01

    Full Text Available Abstract A large investment is required to develop, license and deploy a new antimalarial drug. Too often, that investment has been rapidly devalued by the selection of parasite populations resistant to the drug action. To understand the mechanisms of selection, detailed information on the patterns of drug use in a variety of environments, and the geographic and temporal patterns of resistance is needed. Currently, there is no publically-accessible central database that contains information on the levels of resistance to antimalaria drugs. This paper outlines the resources that are available and the steps that might be taken to create a dynamic, open access database that would include current and historical data on clinical efficacy, in vitro responses and molecular markers related to drug resistance in Plasmodium falciparum and Plasmodium vivax. The goal is to include historical and current data on resistance to commonly used drugs, like chloroquine and sulfadoxine-pyrimethamine, and on the many combinations that are now being tested in different settings. The database will be accessible to all on the Web. The information in such a database will inform optimal utilization of current drugs and sustain the longest possible therapeutic life of newly introduced drugs and combinations. The database will protect the valuable investment represented by the development and deployment of novel therapies for malaria.

  6. Synthesis in aqueous medium and organic praseodymium complexes with ligands derived from Schiff base quinolinic. Characterization and physicochemical study

    International Nuclear Information System (INIS)

    It was investigated the coordination ability of the quinolinic Schiff base organic tetradentate quinolinic ligand (Q Schiff-(OH)2) towards the trivalent praseodymium by UV/Vis spectrophotometric titration (St). By St, was studied the formed species between the Q Schiff-(OH)2 ligand and the praseodymium nitrate salt in equimolar concentrations (5.86 x 10-4 M: 5.22 x 10-4 M) in methanol. The statistical analysis of the experimental results suggested three complexed species with 1Pr:3L, 1Pr:2L y 1Pr:1L stoichiometries. The predominant stoichiometries were the second and the latter. Based on these results and data from the scientific literature, the methodology for the syntheses of the complexes Q Schiff-(OH)2-Pr in aqueous-organic and organic media was established and a molar ratio M:L= 1:2 of praseodymium nitrate and the ligand was used. The new complexes were characterized by UV/Vis, Infrared, X-ray Photoelectron Spectroscopy (XP S), Diffuse Reflectance (Dr) and Thermogravimetric Analysis/Differential Scanning Calorimetry (TGA/DSC). Elemental analysis of C, N, O and Pr by XP S suggested 1Pr:2L:1Na (PrC32H20N4O4Na) stoichiometry of the complex synthesized by the aqueous-organic medium while for the complex synthesized by the organic medium it was 1Pr:3L (PrC48H33N6O6). In the first case, the praseodymium ion charge was neutralized by the anionic ligands whose remaining charge was compensated by the sodium ion. In the second case, the ion charge was neutralized by the ligands. The minimum formula was Pr(Q Schiff)2Na for the pure coordination compound from the aqueous-organic medium and the minimum formula Pr(Q Schiff)3 for that from the organic medium. XP S also indicated that the oxidation state of praseodymium ion was maintained. Both complexes were stable in methanol, ethanol and acetonitrile at least for 5 days. The photophysical properties of the studied complexes were evaluated by emission and excitation luminescence (fluorescence and phosphorescence) at ambient

  7. Synthesis of triazol derivatives of lupeol with potential antimalarial activity

    Directory of Open Access Journals (Sweden)

    Tatiane Freitas Borgati

    2012-06-01

    Full Text Available The goal of this project is synthesize and characterization of derivatives of lupeol and evaluated antimalarial activity. Historically, plants are important source of antimalarial medicines, highlighting quinine (1 (Figure 1, an important      alkaloid from the Cinchona calisaya bark. This compound was an important model for cloroquine  synthesis, a drug that was widely used in malaria treatment. In addition, one of the principal medicines used today is artemisinine, isolated from the Chinese plant Artemisia annua L (2 (Figure 1, and their semi synthetic derivatives (artesunate, artemeter, arteter. However, the malaria parasite has already shown resistance    to most of these current drugs and  the search for new candidates is essential. Lupeol (3 (Figura 1 is a compound that occurs in many plant species and discloses antimalarial, antiinflamatoryl and antitumoral activities. Considering its potential as a lead antimalarial molecule, we focused our work in the synthesis of new lupeol derivatives with increased antimalarial activity(scheme 1.

  8. Use and quality of antimalarial drugs in the private sector in Viet Nam.

    OpenAIRE

    Cong, L D; Yen, P. T.; Nhu, T. V.; Binh, L N

    1998-01-01

    This study examines the use and quality of antimalarial drugs in the growing private sector of Viet Nam. The practices of drug vendors (called alternative treatment providers (ATPs)) as well as their stocks and the quality of drugs sold by them, and the local production and distribution of antimalarials were investigated. Antimalarials were sold by the vast majority of ATPs, almost all the common antimalarials being available for sale. The practices and indications for sale, however, varied. ...

  9. 7-[(Morpholin-4-yl(phenylmethyl]quinolin-8-ol

    Directory of Open Access Journals (Sweden)

    A. Crochet

    2013-01-01

    Full Text Available In the title compound, C20H20N2O2, the quinoline ring system makes dihedral angles of 81.05 (4 and 61.16 (5° with the mean planes of the benzene and morpholine rings, respectively; the mean planes of the latter two rings make a dihedral angle of 83.59 (4°. In the crystal, pairs of O—H...N hydrogen bonds link neighbouring molecules related by a twofold rotation axis, generating R22(10 motifs.

  10. Quinine dimers are potent inhibitors of the Plasmodium falciparum chloroquine resistance transporter and are active against quinoline-resistant P. falciparum.

    Science.gov (United States)

    Hrycyna, Christine A; Summers, Robert L; Lehane, Adele M; Pires, Marcos M; Namanja, Hilda; Bohn, Kelsey; Kuriakose, Jerrin; Ferdig, Michael; Henrich, Philipp P; Fidock, David A; Kirk, Kiaran; Chmielewski, Jean; Martin, Rowena E

    2014-03-21

    Chloroquine (CQ) resistance in the human malaria parasite Plasmodium falciparum is primarily conferred by mutations in the "chloroquine resistance transporter" (PfCRT). The resistance-conferring form of PfCRT (PfCRT(CQR)) mediates CQ resistance by effluxing the drug from the parasite's digestive vacuole, the acidic compartment in which CQ exerts its antiplasmodial effect. PfCRT(CQR) can also decrease the parasite's susceptibility to other quinoline drugs, including the current antimalarials quinine and amodiaquine. Here we describe interactions between PfCRT(CQR) and a series of dimeric quinine molecules using a Xenopus laevis oocyte system for the heterologous expression of PfCRT and using an assay that detects the drug-associated efflux of H(+) ions from the digestive vacuole in parasites that harbor different forms of PfCRT. The antiplasmodial activities of dimers 1 and 6 were also examined in vitro (against drug-sensitive and drug-resistant strains of P. falciparum) and in vivo (against drug-sensitive P. berghei). Our data reveal that the quinine dimers are the most potent inhibitors of PfCRT(CQR) reported to date. Furthermore, the lead compounds (1 and 6) were not effluxed by PfCRT(CQR) from the digestive vacuole but instead accumulated to very high levels within this organelle. Both 1 and 6 exhibited in vitro antiplasmodial activities that were inversely correlated with CQ. Moreover, the additional parasiticidal effect exerted by 1 and 6 in the drug-resistant parasites was attributable, at least in part, to their ability to inhibit PfCRT(CQR). This highlights the potential for devising new antimalarial therapies that exploit inherent weaknesses in a key resistance mechanism of P. falciparum.

  11. Febuxostat methanol solvate

    Directory of Open Access Journals (Sweden)

    Qi-Ying Jiang

    2011-05-01

    Full Text Available In the title compound {systematic name: [2-(3-cyano-4-isobutyloxyphenyl-4-methyl-1,3-thiazole-5-carboxylic acid (febuxostat methanol monosolvate}, C16H16N2O3S·CH4O, the benzene and thiazole rings in the febuxostat molecule are twisted at 5.3 (1°. In the crystal structure, intermolecular O—H...O and O—H...N hydrogen bonds link the febuxostat and methanol molecules into helical chains along the 21 screw axis.

  12. Stevioside methanol tetrasolvate

    OpenAIRE

    Avery, Mitchell A.; McChesney, James D.; Ibrahim, Mohamed A; Douglas L. Rodenburg; Yunshan Wu

    2013-01-01

    Stevioside is a naturally occurring diterpenoid glycoside in Stevia rebaudiana Bertoni. The title compound, C38H60O18·4CH3OH, crystallized as its methanol tetrasolvate. Stevioside consists of an aglycone steviol (a tetracyclic diterpene in which the four-fused-ring system consists of three six-membered rings and one five-membered ring) and a sugar part (three glucose units). A weak intramolecular O—H...O hydrogen bond occurs. In the crystal, the methanol molecules participate in a ...

  13. Artemisinin: An Evolving Antimalarial-Part One

    Directory of Open Access Journals (Sweden)

    Nkereuwem Jonathan Edikpo

    2013-12-01

    Full Text Available This review was conceived with the aim of presenting a compact, yet engaging account of the evolution of artemisinin from its humble and ancient origins as an herbal remedy to a modern chemotherapeutic agent, highlighting its unique pharmacological and toxicological profile and the central position it occupies at present in the battle against malaria. Artemisinin is a sesquiterpene lactone end operoxide with a long and enchanting history. The Chinese had been using concoctions of Artemisia for the treatment of various febrile ailments for close to two millennia. The impetus for its extraction in 1972 from Artemisia annua came from the battlefields of the Vietnamese war of 1965 to 1973 and the political milieu of the Cultural Revolution that encouraged an inward-looking disposition. Owing to solubility problems with the parent compound, artemisinin other semi-synthetic derivatives are now available and include artesunate, artemether, dihydroartemisinin and arteether. Parasiticidal action resides in the endoperoxide moiety which is also primarily responsible for the toxicity of the artemisinin compounds. As a class, they are the most rapidly acting antimalarial chemotherapeutic agents ever in use, reducing initial parasite burden by a factor of 104 per cycle of schizogony. Despite this, high rate of recrudescence occur with monotherapies which necessitates their use in combination with longer acting agents- ACTs. The basis of this high recrudescence is not unrelated to short plasma half-lives, dormancy phenomenon and autoinduction of the metabolizing enzymes. Though safe in humans at recommended dosages, animal studies have continually revealed disturbing side effects most notably, neurotoxicity and, reproductive toxicity manifesting in the twin phenomenon of embryolethality and fetal dysmorphogenesis. In the light of the cautionary tale of thalidomide tragedy, it may not be wise to totally ignore these findings in experimental animals.

  14. Direct Methanol Fuel Cell, DMFC

    Directory of Open Access Journals (Sweden)

    Amornpitoksuk, P.

    2003-09-01

    Full Text Available Direct Methanol Fuel Cell, DMFC is a kind of fuel cell using methanol as a fuel for electric producing. Methanol is low cost chemical substance and it is less harmful than that of hydrogen fuel. From these reasons it can be commercial product. The electrocatalytic reaction of methanol fuel uses Pt-Ru metals as the most efficient catalyst. In addition, the property of membrane and system designation are also effect to the fuel cell efficient. Because of low power of methanol fuel cell therefore, direct methanol fuel cell is proper to use for the energy source of small electrical devices and vehicles etc.

  15. The interaction of x-rays and antimalarials

    International Nuclear Information System (INIS)

    Full text: The radiation sensitivity of malaria parasites has three potential clinical applications, namely i) to prevent the transmission of malaria by blood transfusion, ii) as adjunctive therapy when a radioactive isotope is complexed to a conventional antimalarial drug, and iii) to attenuate the pathogenicity of specific parasite stages as part of the development of a vaccine. In the first two applications, detailed information relating to parasite radiosensitivity and the interaction of ionising radiation with antimalarials is of vital importance because dosimetry must allow for the exposure of normal cells. Malaria parasite cultures (Plasmodium falciparum) were exposed to a logarithmic series of concentrations of antimalarial agents and irradiated using a Siemens Stabilipan orthovoltage radiotherapy unit. The irradiation was performed at room temperature and ambient oxygen concentration. Control samples were also irradiated. The DNA synthesis in each culture was measured 48 hours post irradiation by using a 3H-hypoxanthine incorporation assay. The antimalarials studied are: artesunate, quinine, retinol and chloroquine. The radiosensitivity of Plasmodium falciparum is not dependent on the strain of parasite with the dose required to inhibit 50% of DNA synthesis (ID50) equal to 24.7 ± 3.0 Gy. This applies equally for the drug resistant and drug sensitive strains studied. Because the measured radiosensitivity is dependent on the sera oxygen concentration, the reported value for the ID50 may not apply in hypoxic situations. The interaction of ionising radiation with the antimalarials shows synergy with retinol and choloquine, additivity with quinine and slight antagonism with artesunate. Radionuclide therapy may emerge as a novel treatment for malaria. If this does occur, then, although all strains appear to be equally radiosensitive, care must be taken when combining ionising radiation with existing antimalarials for the treatment of malaria. Copyright (2001

  16. Anti-malarial Drug Design by Targeting Apicoplasts: New Perspectives

    Directory of Open Access Journals (Sweden)

    Avinaba Mukherjee

    2016-03-01

    Full Text Available Objectives: Malaria has been a major global health problem in recent times with increasing mortality. Current treatment methods include parasiticidal drugs and vaccinations. However, resistance among malarial parasites to the existing drugs has emerged as a significant area of concern in anti-malarial drug design. Researchers are now desperately looking for new targets to develop anti-malarials drug which is more target specific. Malarial parasites harbor a plastid-like organelle known as the ‘apicoplast’, which is thought to provide an exciting new outlook for the development of drugs to be used against the parasite. This review elaborates on the current state of development of novel compounds targeted againstemerging malaria parasites. Methods: The apicoplast, originates by an endosymbiotic process, contains a range of metabolic pathways and housekeeping processes that differ from the host body and thereby presents ideal strategies for anti-malarial drug therapy. Drugs are designed by targeting the unique mechanism of the apicoplasts genetic machinery. Several anabolic and catabolic processes, like fatty acid, isopenetyl diphosphate and heme synthess in this organelle, have also been targeted by drugs. Results: Apicoplasts offer exciting opportunities for the development of malarial treatment specific drugs have been found to act by disrupting this organelle’s function, which wouldimpede the survival of the parasite. Conclusion: Recent advanced drugs, their modes of action, and their advantages in the treatment of malaria by using apicoplasts as a target are discussed in this review which thought to be very useful in desigining anti-malarial drugs. Targetting the genetic machinery of apicoplast shows a great advantange regarding anti-malarial drug design. Critical knowledge of these new drugs would give a healthier understanding for deciphering the mechanism of action of anti-malarial drugs when targeting apicoplasts to overcome drug

  17. The antimalarial drug quinine interferes with serotonin biosynthesis and action

    DEFF Research Database (Denmark)

    Islahudin, Farida; Tindall, Sarah M.; Mellor, Ian R.;

    2014-01-01

    The major antimalarial drug quinine perturbs uptake of the essential amino acid tryptophan, and patients with low plasma tryptophan are predisposed to adverse quinine reactions; symptoms of which are similar to indications of tryptophan depletion. As tryptophan is a precursor of the neurotransmit......The major antimalarial drug quinine perturbs uptake of the essential amino acid tryptophan, and patients with low plasma tryptophan are predisposed to adverse quinine reactions; symptoms of which are similar to indications of tryptophan depletion. As tryptophan is a precursor...

  18. True Niacin Deficiency in Quinolinic Acid Phosphoribosyltransferase (QPRT) Knockout Mice.

    Science.gov (United States)

    Shibata, Katsumi

    2015-01-01

    Pyridine nucleotide coenzymes (PNCs) are involved in over 500 enzyme reactions. PNCs are biosynthesized from the amino acid L-tryptophan (L-Trp), as well as the vitamin niacin. Hence, "true" niacin-deficient animals cannot be "created" using nutritional techniques. We wanted to establish a truly niacin-deficient model animal using a protocol that did not involve manipulating dietary L-Trp. We generated mice that are missing the quinolinic acid phosphoribosyltransferase (QPRT) gene. QPRT activity was not detected in qprt(-/-)mice. The qprt(+/+), qprt(+/-) or qprt(-/-) mice (8 wk old) were fed a complete diet containing 30 mg nicotinic acid (NiA) and 2.3 g L-Trp/kg diet or an NiA-free diet containing 2.3 g L-Trp/kg diet for 23 d. When qprt(-/-)mice were fed a complete diet, food intake and body weight gain did not differ from those of the qprt(+/+) and the qprt(+/-) mice. On the other hand, in the qprt(-/-) mice fed the NiA-free diet, food intake and body weight were reduced to 60% (pniacin such as blood and liver NAD concentrations were also lower in the qprt(-/-) mice than in the qprt(+/+) and the qprt(+/-) mice. Urinary excretion of quinolinic acid was greater in the qprt(-/-) mice than in the qprt(+/+) and the qprt(+/-) mice (pniacin-deficient mice.

  19. Genotoxicity risk assessment of diversely substituted quinolines using the SOS chromotest.

    Science.gov (United States)

    Duran, Leidy Tatiana Díaz; Rincón, Nathalia Olivar; Galvis, Carlos Eduardo Puerto; Kouznetsov, Vladimir V; Lorenzo, Jorge Luis Fuentes

    2015-03-01

    Quinolines are aromatic nitrogen compounds with wide therapeutic potential to treat parasitic and microbial diseases. In this study, the genotoxicity of quinoline, 4-methylquinoline, 4-nitroquinoline-1-oxide (4-NQO), and diversely functionalized quinoline derivatives and the influence of the substituents (functional groups and/or atoms) on their genotoxicity were tested using the SOS chromotest. Quinoline derivatives that induce genotoxicity by the formation of an enamine epoxide structure did not induce the SOS response in Escherichia coli PQ37 cells, with the exception of 4-methylquinoline that was weakly genotoxic. The chemical nature of the substitution (C-5 to C-8: hydroxyl, nitro, methyl, isopropyl, chlorine, fluorine, and iodine atoms; C-2: phenyl and 3,4-methylenedioxyphenyl rings) of quinoline skeleton did not significantly modify compound genotoxicities; however, C-2 substitution with α-, β-, or γ-pyridinyl groups removed 4-methylquinoline genotoxicity. On the other hand, 4-NQO derivatives whose genotoxic mechanism involves reduction of the C-4 nitro group were strong inducers of the SOS response. Methyl and nitrophenyl substituents at C-2 of 4-NQO core affected the genotoxic potency of this molecule. The relevance of these results is discussed in relation to the potential use of the substituted quinolines. The work showed the sensitivity of SOS chromotest for studying structure-genotoxicity relationships and bioassay-guided quinoline synthesis.

  20. In vitro Potentiation of Antimalarial Activities by Daphnetin Derivatives Against Plasmodium falciparum

    Institute of Scientific and Technical Information of China (English)

    FANG HUANG; LIN-HUA TANG; LIN-QIAN YU; YI-CHANG NI; QIN-MEI WANG; FA-JUN NAN

    2006-01-01

    Objective To screen the antimalarial compounds of daphnetin derivatives against Plasmodium falciparum in vitro. Method Plasmodium faciparum (FCC1) was cultured in vitro by a modified method of Trager and Jensen. Antimalarial compounds were screened by microscopy-based assay and microfluorimetric method. Results DA79 and DA78 showed potent antimalarial activity against Plasmodium falciparum cultured in vitro. Conclusion Though the relationship between the structures of daphnetin derivatives and their antimalarial activities has not been clarified yet, this study may provide a new direction for discovery of more potential antimalarial compounds.

  1. Protein from methanol

    Energy Technology Data Exchange (ETDEWEB)

    Rosenzweig, M.; Ushio, S.

    1974-01-07

    The biosynthesis of proteins from methanol produced from natural gas can provide an attractive alternative to the already commercially proven technique of protein synthesis from gas oil and n-paraffin feedstocks if current pilot-plant tests in England and Japan prove successful. The methanol route also provides other advantages as a protein feedstock: it is water soluble, contains no polycyclic aromatic compounds, and requires less oxygen than methane. Its lower boiling point helps ease the separation of feedstock from the product stream. Finally, it will require lower investment costs. Both ICI and Mitsubishi Gas Chemical Co. are large methanol producers. ICI already has a 1000 ton/yr plant operating at Teeside, England, and expects to decide on a 100,000 m ton/yr plant later this year. Mitsubishi is constructing a large-scale pilot plant scheduled to come onstream this year. ICI will use a Pseudomona bacterium at 98.6/sup 0/F (37/sup 0/C) in the fermenter. Mitsubishi has not yet decided on a yeast or a bacteria, and is searching for a strain capable of withstanding up to 115/sup 0/F (46/sup 0/C). In the more advanced ICI process, methanol will be mixed with phosphoric acid, potassium sulfate, sodium chloride, and traces of iron, copper, zinc, and molybdenum; diluted with water; passed through a sterilization tank; and fermented at pH 7 in a pressure cycle fermenter. The product stream, containing a 3 percent suspension of cellular dry matter, is taken near the top of the fermenter riser, then passed through a flotation vessel and a centrifuge to pack the cell concentration to 20 percent. Water is recycled. Whatever methanol remains in the fermenter product stream is either used up by the microorganisms in subsequent processing or vaporized in the dryer. (auth)

  2. Synthesis and biological activity of pyrimido [1, 2-a] quinoline moiety and its 2-substituted derivatives

    Science.gov (United States)

    Jadhav, A. G.; Halikar, N. K.

    2013-04-01

    2-Amino-3-cyano quinoline (1) and bis (methylthio) methylene malononitrile (2) were refluxed in N,N-dimethyl formamide (DMF) in presence of catalytic amount of anhydrous potassium carbonate to afforded 3, 11-dicyano-4-imino-2-methylthio -4H-pyrimido [1, 2-a] quinoline (3). The latter were further reacted with different substituted aniline, phenol, hetryl amine and compound containing active methyl group. Afforded to 3, 11-dicyano-4-imino -4H-pyrimido [1, 2-a] quinoline and their 2-substuited derivatives (4a-7c). All these newly synthesized compounds were characterized by elemental analysis and spectral data, and screened for their antimicrobial activities.

  3. Anaerobic Treatment of Methanolic Wastes

    NARCIS (Netherlands)

    Lettinga, G.; Geest, van der A.Th.; Hobma, S.W.; Laan, van der J.B.R.

    1979-01-01

    Although it is well known that methanol can be fermented directly by a specific species of methane bacteria, viz. Methanosarcina barkeri, until now little information was available about the effect of important environmental factors on the anaerobic fermentation of methanol. As methanol can be the m

  4. Dried whole plant Artemisia annua as an antimalarial therapy.

    Directory of Open Access Journals (Sweden)

    Mostafa A Elfawal

    2012-12-01

    Full Text Available Drugs are primary weapons for reducing malaria in human populations. However emergence of resistant parasites has repeatedly curtailed the lifespan of each drug that is developed and deployed. Currently the most effective anti-malarial is artemisinin, which is extracted from the leaves of Artemisia annua. Due to poor pharmacokinetic properties and prudent efforts to curtail resistance to monotherapies, artemisinin is prescribed only in combination with other anti-malarials composing an Artemisinin Combination Therapy (ACT. Low yield in the plant, and the added cost of secondary anti-malarials in the ACT, make artemisinin costly for the developing world. As an alternative, we compared the efficacy of oral delivery of the dried leaves of whole plant (WP A. annua to a comparable dose of pure artemisinin in a rodent malaria model (Plasmodium chabaudi. We found that a single dose of WP (containing 24 mg/kg artemisinin reduces parasitemia more effectively than a comparable dose of purified drug. This increased efficacy may result from a documented 40-fold increase in the bioavailability of artemisinin in the blood of mice fed the whole plant, in comparison to those administered synthetic drug. Synergistic benefits may derive from the presence of other anti-malarial compounds in A. annua. If shown to be clinically efficacious, well-tolerated, and compatible with the public health imperative of forestalling evolution of drug resistance, inexpensive, locally grown and processed A. annua might prove to be an effective addition to the global effort to reduce malaria morbidity and mortality.

  5. In vitro antimalarial activity of novel semisynthetic nocathiacin I antibiotics.

    Science.gov (United States)

    Sharma, Indu; Sullivan, Margery; McCutchan, Thomas F

    2015-01-01

    Presently, the arsenal of antimalarial drugs is limited and needs to be replenished. We evaluated the potential antimalarial activity of two water-soluble derivatives of nocathiacin (BMS461996 and BMS411886) against the asexual blood stages of Plasmodium falciparum. Nocathiacins are a thiazolyl peptide group of antibiotics, are structurally related to thiostrepton, have potent activity against a wide spectrum of multidrug-resistant Gram-positive bacteria, and inhibit protein synthesis. The in vitro growth inhibition assay was done using three laboratory strains of P. falciparum displaying various levels of chloroquine (CQ) susceptibility. Our results indicate that BMS461996 has potent antimalarial activity and inhibits parasite growth with mean 50% inhibitory concentrations (IC50s) of 51.55 nM for P. falciparum 3D7 (CQ susceptible), 85.67 nM for P. falciparum Dd2 (accelerated resistance to multiple drugs [ARMD]), and 99.44 nM for P. falciparum K1 (resistant to CQ, pyrimethamine, and sulfadoxine). Similar results at approximately 7-fold higher IC50s were obtained with BMS411886 than with BMS461996. We also tested the effect of BMS491996 on gametocytes; our results show that at a 20-fold excess of the mean IC50, gametocytes were deformed with a pyknotic nucleus and growth of stage I to IV gametocytes was arrested. This preliminary study shows a significant potential for nocathiacin analogues to be developed as antimalarial drug candidates and to warrant further investigation. PMID:25779576

  6. Direct Methanol Fuel Cell, DMFC

    OpenAIRE

    Amornpitoksuk, P.

    2003-01-01

    Direct Methanol Fuel Cell, DMFC is a kind of fuel cell using methanol as a fuel for electric producing. Methanol is low cost chemical substance and it is less harmful than that of hydrogen fuel. From these reasons it can be commercial product. The electrocatalytic reaction of methanol fuel uses Pt-Ru metals as the most efficient catalyst. In addition, the property of membrane and system designation are also effect to the fuel cell efficient. Because of low power of methanol fuel cell therefor...

  7. Stevioside methanol tetrasolvate

    Directory of Open Access Journals (Sweden)

    Mitchell A. Avery

    2013-03-01

    Full Text Available Stevioside is a naturally occurring diterpenoid glycoside in Stevia rebaudiana Bertoni. The title compound, C38H60O18·4CH3OH, crystallized as its methanol tetrasolvate. Stevioside consists of an aglycone steviol (a tetracyclic diterpene in which the four-fused-ring system consists of three six-membered rings and one five-membered ring and a sugar part (three glucose units. A weak intramolecular O—H...O hydrogen bond occurs. In the crystal, the methanol molecules participate in a two-dimensional hydrogen-bonded network parallel to b axis with the sugars and together they form a hydrophilic tunnel which encloses the lipophilic part of the molecule.

  8. Coordination chemistry and biological activity of 5'-OH modified quinoline-B12 derivatives.

    Science.gov (United States)

    Zelenka, Karel; Brandl, Helmut; Spingler, Bernhard; Zelder, Felix

    2011-10-14

    The consequences of structural modifications at the 5'-OH ribofuranotide moiety of quinoline modified B12 derivatives are discussed in regard of the coordination chemistry, the electrochemical properties and the biological behaviour of the compound.

  9. Quinolinic Acid: An Endogenous Neurotoxin with Multiple Targets

    Directory of Open Access Journals (Sweden)

    Rafael Lugo-Huitrón

    2013-01-01

    Full Text Available Quinolinic acid (QUIN, a neuroactive metabolite of the kynurenine pathway, is normally presented in nanomolar concentrations in human brain and cerebrospinal fluid (CSF and is often implicated in the pathogenesis of a variety of human neurological diseases. QUIN is an agonist of N-methyl-D-aspartate (NMDA receptor, and it has a high in vivo potency as an excitotoxin. In fact, although QUIN has an uptake system, its neuronal degradation enzyme is rapidly saturated, and the rest of extracellular QUIN can continue stimulating the NMDA receptor. However, its toxicity cannot be fully explained by its activation of NMDA receptors it is likely that additional mechanisms may also be involved. In this review we describe some of the most relevant targets of QUIN neurotoxicity which involves presynaptic receptors, energetic dysfunction, oxidative stress, transcription factors, cytoskeletal disruption, behavior alterations, and cell death.

  10. The Methanol Economy Project

    Energy Technology Data Exchange (ETDEWEB)

    Olah, George; Prakash, G. K.

    2013-12-31

    The Methanol Economy Project is based on the concept of replacing fossil fuels with methanol generated either from renewable resources or abundant natural (shale) gas. The full methanol cycle was investigated in this project, from production of methanol through bromination of methane, bireforming of methane to syngas, CO{sub 2} capture using supported amines, co-electrolysis of CO{sub 2} and water to formate and syngas, decomposition of formate to CO{sub 2} and H{sub 2}, and use of formic acid in a direct formic acid fuel cell. Each of these projects achieved milestones and provided new insights into their respective fields.  Direct electrophilic bromination of methane to methyl bromide followed by hydrolysis to yield methanol was investigated on a wide variety of catalyst systems, but hydrolysis proved impractical for large-scale industrial application.  Bireforming the correct ratio of methane, CO{sub 2}, and water on a NiO / MgO catalyst yielded the right proportion of H{sub 2}:CO (2:1) and proved to be stable for at least 250 hours of operation at 400 psi (28 atm).  CO{sub 2} capture utilizing supported polyethyleneimines yielded a system capable of adsorbing CO{sub 2} from the air and release at nominal temperatures with negligible amine leaching.  CO{sub 2} electrolysis to formate and syngas showed considerable increases in rate and selectivity by performing the reaction in a high pressure flow electrolyzer.  Formic acid was shown to decompose selectively to CO{sub 2} and H{sub 2} using either Ru or Ir based homogeneous catalysts.  Direct formic acid fuel cells were also investigated and showed higher than 40% voltage efficiency using reduced loadings of precious metals. A technoeconomic analysis was conducted to assess the viability of taking each of these processes to the industrial scale by applying the data gathered during the experiments to approximations based on currently used industrial processes. Several of these processes show

  11. 4-Hy-droxy-1-methyl-3-phenyl-quinolin-2(1H)-one.

    Science.gov (United States)

    Kafka, Stanislav; Pevec, Andrej; Proisl, Karel; Kimmel, Roman; Košmrlj, Janez

    2013-02-01

    In the title compound, C(16)H(13)NO(2), the quinoline system is approximately planar with a maximum deviation from the least-squares plane of 0.059 (1) Å for the N atom. The phenyl ring is rotated by 62.16 (4)° with respect to the plane of the quinoline system. In the crystal, O-H⋯O hydrogen bonds link mol-ecules into infinite chains running along the b-axis direction.

  12. A quinoline based pH sensitive ratiometric fluorescent sensor: Structure and spectroscopy

    Indian Academy of Sciences (India)

    Soma Mukherjee; Amit Kumar Paul; Helen Stoeckli-Evans

    2015-09-01

    A new quinoline based hydrazone was synthesized via a condensation reaction and characterized by NMR, mass and single crystal X-ray diffraction studies. It was investigated for suitability as a reversible ratiometric fluorescent pH sensor in acidic pH region. The sensor exhibits intramolecular charge transfer (ICT) type photophysical changes upon protonation of the quinoline ring. No significant interference on emission behavior was observed in the presence of various metal ions.

  13. Activated carbon fibers prepared from quinoline and isoquinoline pitches

    Energy Technology Data Exchange (ETDEWEB)

    Mochida, I.; An, K.; Korai, Y. [Kyushu University, Fukuoka (Japan). Institute of Advanced Material Study; Kojima, T.; Komatsu, M. [Mitsubishi Gas Chemical Co. Inc., Tokyo (Japan); Yoshikawa, M. [Osaka Gas Co. Ltd., Osaka (Japan)

    1998-11-01

    Nitrogen enriched activated carbon fibers (ACFs) were prepared from isotropic quinoline and isoquinoline pitches produced by the catalytic action of HF/BF3 through spinning, stabilization, carbonization, and oxidative activation. The pitches exhibited excellent spinnability, and the resultant fibers had mechanical properties comparable to those of commercial fibers. The surface areas and nitrogen contents of the ACFs, obtained hereby were 740-860 m{sup 2}/g and 4-5.6%, respectively, at around 50 wt% of burn-off. FT-IR and XPS analyses identified the surface oxygen and nitrogen functional groups on the stabilized and activated fibers. The ACFs from isoquinoline pitch (IQP-ACF) exhibited higher basicity (l.3 meq/g) than commercial ACFs of similar surface areas (0.68 and 0.25 meq/g for PAN (FE-300) and coal tar pitch (OG-8A) based ACFs, respectively) due to a higher basic nitrogen content on the surface. The activation appears to expose basic nitrogen atoms, which were located under the surface. The basicity of ACF from quinoline pitch (QP-ACF) was much lower than that of IQP-ACF, however, QP-ACF adsorbed 74 mg/g of SO2, which was 1.4 and 2.3 times higher than that over FE-300 and OG-8A. In contrast, IQP-ACFs showed less adsorption of SO2 than that of QP-ACF and FE-300, but more than that of OG-8A. Oxidation activity of ACF surface may participate in the adsorption of SO2 in the form of SO3 or H2SO4. The oxygen functional groups under the influence of neighboring nitrogen atoms may be the active sites for the oxidative adsorption. 15 refs., 8 figs., 4 tabs.

  14. Assessment of Markers of Antimalarial Drug Resistance in Plasmodium falciparum Isolates from Pregnant Women in Lagos, Nigeria.

    Directory of Open Access Journals (Sweden)

    Chimere Obiora Agomo

    Full Text Available The use of antimalarial drugs for prevention and treatment is a major strategy in the prevention of malaria in pregnancy. Although sulphadoxine-pyrimethamine (SP is currently recommended for intermittent preventive treatment of malaria during pregnancy in Nigeria, previously used drugs for prophylaxis such as chloroquine (CQ and pyrimethamine are accessible as they are purchased over the counter. This study describes the markers of absence or presence of resistance to quinoline (Pfcrt and Pfmdr 1 and type 1 antifolate antimalarial medicines (Pfdhfr.Plasmodium falciparum-positive dried blood spots from pregnant women attending antenatal clinics for the first time during current pregnancy were investigated for the presence of mutations at codons 72-76 of Plasmodium falciparum chloroquine resistance transporter (Pfcrt gene by real time polymerase chain reaction (PCR using haplotype-specific probes. PCR followed by sequence analysis was used to identify mutations at codons 86, 184, 1034, 1042 and 1246 of P. falciparum multi-drug resistance-1 (Pfmdr1 gene; and codons 16, 50, 51, 59, 108, 140 and 164 of Pfdhfr gene.Two haplotypes of Pfcrt (n = 54 were observed: CVMNK 13(24.2% and CVIET 41 (75.9% of the samples. The SVMNT haplotype was absent in this population. The Pfmdr1 (n = 28 haplotypes were NYSND 15(53.6%, YYSND 5(17.9%, NFSND 6(21.4% and YFSND 2(7.1%. The Pfdhfr (n = 15 were ACNCSVI 4(26.7%, and ACICNSVI 1(6.7% and ACIRNVI 10 (66.7%. The rate of occurrence of Pfcrt 76T, Pfdhfr108N, Pfmdr186Y and 184F were 75.9%, 73.3%, 25% and 28.1% respectively. The Pfmdr1 86Y was associated with low parasitaemia (median = 71 parasites/μl, P = 0.024 while Pfcrt 76T was associated with young maternal age (mean 24.1 ± 4.5 years; P = 0.006. The median parasitaemia were similar (P>0.05 in wild and mutant strains of Pfcrt 76, Pfmdr1 184 and Pfdhfr 108. There was no association between gravidity or gestational age of the women and presence of mutations in the Pfcrt

  15. Quinolines in clothing textiles--a source of human exposure and wastewater pollution?

    Science.gov (United States)

    Luongo, Giovanna; Thorsén, Gunnar; Ostman, Conny

    2014-05-01

    A production process in which the use of various types of chemicals seems to be ubiquitous makes the textile industry a growing problem regarding both public health as well as the environment. Among several substances used at each stage, the present study focuses on the quinolines, a class of compounds involved in the manufacture of dyes, some of which are skin irritants and/or classified as probable human carcinogens. A method was developed for the determination of quinoline derivatives in textile materials comprising ultrasound-assisted solvent extraction, solid phase extraction cleanup, and final analysis by gas chromatography/mass spectrometry. Quinoline and ten quinoline derivatives were determined in 31 textile samples. The clothing samples, diverse in color, material, brand, country of manufacture, and price, and intended for a broad market, were purchased from different shops in Stockholm, Sweden. Quinoline, a possible human carcinogen, was found to be the most abundant compound present in almost all of the samples investigated, reaching a level of 1.9 mg in a single garment, and it was found that quinoline and its derivatives were mainly correlated to polyester material. This study points out the importance of screening textiles with nontarget analysis to investigate the presence of chemicals in an unbiased manner. Focus should be primarily on clothing worn close to the body.

  16. Quinolines in clothing textiles--a source of human exposure and wastewater pollution?

    Science.gov (United States)

    Luongo, Giovanna; Thorsén, Gunnar; Ostman, Conny

    2014-05-01

    A production process in which the use of various types of chemicals seems to be ubiquitous makes the textile industry a growing problem regarding both public health as well as the environment. Among several substances used at each stage, the present study focuses on the quinolines, a class of compounds involved in the manufacture of dyes, some of which are skin irritants and/or classified as probable human carcinogens. A method was developed for the determination of quinoline derivatives in textile materials comprising ultrasound-assisted solvent extraction, solid phase extraction cleanup, and final analysis by gas chromatography/mass spectrometry. Quinoline and ten quinoline derivatives were determined in 31 textile samples. The clothing samples, diverse in color, material, brand, country of manufacture, and price, and intended for a broad market, were purchased from different shops in Stockholm, Sweden. Quinoline, a possible human carcinogen, was found to be the most abundant compound present in almost all of the samples investigated, reaching a level of 1.9 mg in a single garment, and it was found that quinoline and its derivatives were mainly correlated to polyester material. This study points out the importance of screening textiles with nontarget analysis to investigate the presence of chemicals in an unbiased manner. Focus should be primarily on clothing worn close to the body. PMID:24604325

  17. Crystal Structures of the Iron–Sulfur Cluster-Dependent Quinolinate Synthase in Complex with Dihydroxyacetone Phosphate, Iminoaspartate Analogues, and Quinolinate

    Energy Technology Data Exchange (ETDEWEB)

    Fenwick, Michael K. [Cornell Univ., Ithaca, NY (United States); Ealick, Steven E. [Cornell Univ., Ithaca, NY (United States)

    2016-07-12

    The quinolinate synthase of prokaryotes and photosynthetic eukaryotes, NadA, contains a [4Fe-4S] cluster with unknown function. We report crystal structures of Pyrococcus horikoshii NadA in complex with dihydroxyacetone phosphate (DHAP), iminoaspartate analogues, and quinolinate. DHAP adopts a nearly planar conformation and chelates the [4Fe-4S] cluster via its keto and hydroxyl groups. The active site architecture suggests that the cluster acts as a Lewis acid in enediolate formation, like zinc in class II aldolases. The DHAP and putative iminoaspartate structures suggest a model for a condensed intermediate. The ensemble of structures suggests a two-state system, which may be exploited in early steps.

  18. Atmospheric methanol measurement using selective catalytic methanol to formaldehyde conversion

    Directory of Open Access Journals (Sweden)

    S. J. Solomon

    2005-05-01

    Full Text Available A novel atmospheric methanol measurement technique, employing selective gas-phase catalytic conversion of methanol to formaldehyde followed by detection of the formaldehyde product, has been developed and tested. The effects of temperature, gas flow rate, gas composition, reactor-bed length, and reactor-bed composition on the methanol conversion efficiency of a molybdenum-rich, iron-molybdate catalyst [Mo-Fe-O] were studied. Best results were achieved using a 1:4 mixture (w/w of the catalyst in quartz sand. Optimal methanol to formaldehyde conversion (>95% efficiency occurred at a catalyst housing temperature of 345°C and an estimated sample-air/catalyst contact time of <0.2 s. Potential interferences arising from conversion of methane and a number of common volatile organic compounds (VOC to formaldehyde were found to be negligible under most atmospheric conditions and catalyst housing temperatures. Using the new technique, atmospheric measurements of methanol were made at the University of Bremen campus from 1 to 15 July 2004. Methanol mixing ratios ranged from 1 to 5 ppb with distinct maxima at night. Formaldehyde mixing ratios, obtained in conjunction with methanol by periodically bypassing the catalytic converter, ranged from 0.2 to 1.6 ppb with maxima during midday. These results suggest that selective, catalytic methanol to formaldehyde conversion, coupled with existing formaldehyde measurement instrumentation, is an inexpensive and effective means for monitoring atmospheric methanol.

  19. Atmospheric methanol measurement using selective catalytic methanol to formaldehyde conversion

    Directory of Open Access Journals (Sweden)

    S. J. Solomon

    2005-01-01

    Full Text Available A novel atmospheric methanol measurement technique, employing selective gas-phase catalytic conversion of methanol to formaldehyde followed by detection of the formaldehyde product, has been developed and tested. The effects of temperature, gas flow rate, gas composition, reactor-bed length, and reactor-bed composition on the methanol conversion efficiency of a molybdenum-rich, iron-molybdate catalyst [Mo-Fe-O] were studied. Best results were achieved using a 1:4 mixture (w/w of the catalyst in quartz sand. Optimal methanol to formaldehyde conversion (>95% efficiency occurred at a catalyst housing temperature of 345°C and an estimated sample-air/catalyst contact time of <0.2 seconds. Potential interferences arising from conversion of methane and a number of common volatile organic compounds (VOC to formaldehyde were found to be negligible under most atmospheric conditions and catalyst housing temperatures. Using the new technique, atmospheric measurements of methanol were made at the University of Bremen campus from 1 to 15 July 2004. Methanol mixing ratios ranged from 1 to 5 ppb with distinct maxima at night. Formaldehyde mixing ratios, obtained in conjunction with methanol by periodically bypassing the catalytic converter, ranged from 0.2 to 1.6 ppb with maxima during midday. These results suggest that selective, catalytic methanol to formaldehyde conversion, coupled with existing formaldehyde measurement instrumentation, is an inexpensive and effective means for monitoring atmospheric methanol.

  20. CO2 hydrogenation to methanol

    OpenAIRE

    Frilund, Christian

    2016-01-01

    The literature survey discusses the recent developments in heterogeneous catalytic hydrogenation of CO2 to methanol. Special focus was given to new coated catalysts and reactors. Methanol is an important chemical that is currently produced from synthesis gas. Methanol can also be produced from CO2, but the reaction is less thermodynamically favoured. The main reaction is the exothermic CO2 hydrogenation, and there is a competing fast reaction, the reverse water-gas shift, which converts CO2 t...

  1. Fake anti-malarials: start with the facts.

    Science.gov (United States)

    Kaur, Harparkash; Clarke, Siȃn; Lalani, Mirza; Phanouvong, Souly; Guérin, Philippe; McLoughlin, Andrew; Wilson, Benjamin K; Deats, Michael; Plançon, Aline; Hopkins, Heidi; Miranda, Debora; Schellenberg, David

    2016-02-13

    This meeting report presents the key findings and discussion points of a 1-day meeting entitled 'Fake anti-malarials: start with the facts' held on 28th May 2015, in Geneva, Switzerland, to disseminate the findings of the artemisinin combination therapy consortium's drug quality programme. The teams purchased over 10,000 samples, using representative sampling approaches, from six malaria endemic countries: Equatorial Guinea (Bioko Island), Cambodia, Ghana, Nigeria, Rwanda and Tanzania. Laboratory analyses of these samples showed that falsified anti-malarials (fact that the WHO has urged regulatory authorities in malaria-endemic countries to take measures to halt the production and marketing of these oral monotherapies since 2007. This report summarizes the presentations that reviewed the public health impact of falsified and substandard drugs, sampling strategies, techniques for drug quality analysis, approaches to strengthen health systems capacity for the surveillance of drug quality, and the ensuing discussion points from the dissemination meeting.

  2. Hit-to-Lead Studies for the Antimalarial Tetrahydroisoquinolone Carboxanilides.

    Science.gov (United States)

    Floyd, David M; Stein, Philip; Wang, Zheng; Liu, Jian; Castro, Steve; Clark, Julie A; Connelly, Michele; Zhu, Fangyi; Holbrook, Gloria; Matheny, Amy; Sigal, Martina S; Min, Jaeki; Dhinakaran, Rajkumar; Krishnan, Senthil; Bashyum, Sridevi; Knapp, Spencer; Guy, R Kiplin

    2016-09-01

    Phenotypic whole-cell screening in erythrocytic cocultures of Plasmodium falciparum identified a series of dihydroisoquinolones that possessed potent antimalarial activity against multiple resistant strains of P. falciparum in vitro and show no cytotoxicity to mammalian cells. Systematic structure-activity studies revealed relationships between potency and modifications at N-2, C-3, and C-4. Careful structure-property relationship studies, coupled with studies of metabolism, addressed the poor aqueous solubility and metabolic vulnerability, as well as potential toxicological effects, inherent in the more potent primary screening hits such as 10b. Analogues 13h and 13i, with structural modifications at each site, were shown to possess excellent antimalarial activity in vivo. The (+)-(3S,4S) enantiomer of 13i and similar analogues were identified as the more potent. On the basis of these studies, we have selected (+)-13i for further study as a preclinical candidate. PMID:27505686

  3. Synthesis and Antimalarial Activity of Novel Dihydro-Artemisinin Derivatives

    Directory of Open Access Journals (Sweden)

    Jian Wang

    2011-05-01

    Full Text Available The Plasmodium falciparum cysteine protease falcipain-2, one of the most promising targets for antimalarial drug design, plays a key role in parasite survival as a major peptide hydrolase within the hemoglobin degradation pathway. In this work, a series of novel dihydroartemisinin derivatives based on (thiosemicarbazone scaffold were designed and synthesized as potential falcipain-2 inhibitors. The in vitro biological assay indicated that most of the target compounds showed excellent inhibition activity against P. falciparum falcipain-2, with IC50 values in the 0.29–10.63 μM range. Molecular docking studies were performed to investigate the binding affinities and interaction modes for the inhibitors. The preliminary SARs were summarized and could serve as a foundation for further investigation in the development of antimalarial drugs.

  4. Cell wall perturbation sensitizes fungi to the antimalarial drug chloroquine

    OpenAIRE

    Islahudin, Farida; Khozoie, Combiz; Bates, Steven; Ting, Kang-Nee; Pleass, Richard J.; Avery, Simon V.

    2013-01-01

    Chloroquine (CQ) has been a mainstay of antimalarial drug treatment for several decades. Additional therapeutic actions of CQ have been described, including some reports of fungal inhibition. Here we investigated the action of CQ in fungi, including the yeast model Saccharomyces cerevisiae. A genomewide yeast deletion strain collection was screened against CQ, revealing that bck1Δ and slt2Δ mutants of the cell wall integrity pathway are CQ hypersensitive. This phenotype was rescued with sorbi...

  5. Mechanistic Study of the Spiroindolones: A New Class of Antimalarials

    Directory of Open Access Journals (Sweden)

    Thomas H. Keller

    2012-08-01

    Full Text Available During the synthesis of the new antimalarial drug candidate NITD609, a high degree of diastereoselectivity was observed in the Pictet-Spengler reaction. By isolating both the 4E and 4Z imine intermediates, a systematic mechanistic study of the reaction under both kinetic and thermodynamic conditions was conducted. This study provides insight into the source of the diastereoselectivity for this important class of compounds.

  6. Drug resistance genomics of the antimalarial drug artemisinin

    OpenAIRE

    Elizabeth A Winzeler; Manary, Micah J

    2014-01-01

    Across the globe, over 200 million annual malaria infections result in up to 660,000 deaths, 77% of which occur in children under the age of five years. Although prevention is important, malaria deaths are typically prevented by using antimalarial drugs that eliminate symptoms and clear parasites from the blood. Artemisinins are one of the few remaining compound classes that can be used to cure multidrug-resistant Plasmodium falciparum infections. Unfortunately, clinical trials from Southeast...

  7. Intermittent Preventive Antimalarial Treatment for Children with Anaemia.

    OpenAIRE

    Athuman, Mwaka; Kabanywanyi, Abdunoor M; Rohwer, Anke C

    2015-01-01

    Background Anaemia is a global public health problem. Children under five years of age living in developing countries (mostly Africa and South-East Asia) are highly affected. Although the causes for anaemia are multifactorial, malaria has been linked to anaemia in children living in malaria-endemic areas. Administering intermittent preventive antimalarial treatment (IPT) to children might reduce anaemia, since it could protect children from new Plasmodium parasite infection (the parasites tha...

  8. Potential antimalarials from African natural products: a review

    Directory of Open Access Journals (Sweden)

    Bashir Lawal

    2015-12-01

    Full Text Available Ethnopharmacological relevance: Malaria remains an overwhelming infectious disease with significant health challenges in African and other endemic countries globally. Resistance to antimalarial drugs has become one of the most momentous challenges to human health and thus has necessitated the hunt for new and effective drugs. Consequently, few decades have witnessed a surfeit of research geared to validate the effectiveness of commonly used traditionally medicines against malaria fever. The present review work focuses on documenting natural products from African whose activity has been reported in-vivo or invi-tro against malaria parasite. Methods: Literature was collected using electronic search of published articles (Google Scholar, PubMed, Medline, Sciencedirect, Science domain that report on antiplasmodial activity of natural products from differernts Africa region. Results: A Total of 652 plant taxa from 146 families, 134 isolated antimalarial compounds from 39 plants species, 2 herbal formulations and 4 insect/products were found to be reported in literature from 1996 to 2015. Plants species from family Asteraceae (11.04%, Fababceae (8.128%, Euphorbiaceae (5.52%, Rubiaceas (5.52% and Apocyanaceae (5.214%, have received more scientific validation than others. Conclusion: African natural products possess remarkable healing properties as revealed in the various citations as promising antimalarial agents. Some of these natural products from Africa demonstrate high, promising or low activities against plasmodium parasite. This study also shows that natural products from Africa have a huge amount of novel antimalarial compounds that could serve as a leads for the development of new and effective antiplasmodial drugs. However, in a view of bridging the gap in knowledge, clinical validation of these natural products is of paramount importance. [J Intercult Ethnopharmacol 2015; 4(4.000: 318-343

  9. Rational Design of Proteasome Inhibitors as Antimalarial Drugs.

    Science.gov (United States)

    Le Chapelain, Camille; Groll, Michael

    2016-05-23

    One life, two strategies: Crucial structural differences between the human and the Plasmodium falciparum proteasomes were recently identified. A combination of cryo-EM and functional characterization enabled the design of a selective antimalarial proteasome inhibitor that shows low toxicity in the host. When used with artemisinin, this ligand offers a new approach for the efficient treatment of malaria at all stages of the parasite lifecycle.

  10. Antimalarial diterpene alkaloids from the seeds of Caesalpinia minax.

    Science.gov (United States)

    Ma, Guoxu; Sun, Zhaocui; Sun, Zhonghao; Yuan, Jingquan; Wei, Hua; Yang, Junshan; Wu, Haifeng; Xu, Xudong

    2014-06-01

    Two new diterpene alkaloids, caesalminines A (1) and B (2), possessing a tetracyclic cassane-type furanoditerpenoid skeleton with γ-lactam ring, were isolated from the seeds of Caesalpinia minax. Their structures were determined by different spectroscopic methods and ECD calculation. The plausible biosynthetic pathway of caesalminines A and B was proposed. The anti-malarial activity of compounds 1 and 2 is presented with IC50 values of 0.42 and 0.79 μM, respectively.

  11. Antimicrobial peptides: a new class of antimalarial drugs?

    Directory of Open Access Journals (Sweden)

    Nuno eVale

    2014-12-01

    Full Text Available A range of antimicrobial peptides (AMP exhibit activity on malaria parasites, Plasmodium spp, in their blood or mosquito stages, or both. These peptides include a diverse array of both natural and synthetic molecules varying greatly in size, charge, hydrophobicity and secondary structure features. Along with an overview of relevant literature reports regarding AMP that display antiplasmodial activity, this review makes a few considerations about those molecules as a potential new class of antimalarial drugs.

  12. Reactions between arylhydrazinium chlorides and 2-chloroquinoline-3-carbaldehydes: molecular and supramolecular structures of a hydrazone, a 4,9-dihydro-1H-pyrazolo[3,4-b]quinoline and two 1H-pyrazolo[3,4-b]quinolines.

    Science.gov (United States)

    Kumara, Tholappanavara H Suresha; Nagendrappa, Gopalpur; Chandrika, Nanjappa; Sowmya, Haliwana B V; Kaur, Manpreet; Jasinski, Jerry P; Glidewell, Christopher

    2016-09-01

    Hydrazone derivatives exhibit a wide range of biological activities, while pyrazolo[3,4-b]quinoline derivatives, on the other hand, exhibit both antimicrobial and antiviral activity, so that all new derivatives in these chemical classes are potentially of value. Dry grinding of a mixture of 2-chloroquinoline-3-carbaldehyde and 4-methylphenylhydrazinium chloride gives (E)-1-[(2-chloroquinolin-3-yl)methylidene]-2-(4-methylphenyl)hydrazine, C17H14ClN3, (I), while the same regents in methanol in the presence of sodium cyanoborohydride give 1-(4-methylphenyl)-4,9-dihydro-1H-pyrazolo[3,4-b]quinoline, C17H15N3, (II). The reactions between phenylhydrazinium chloride and either 2-chloroquinoline-3-carbaldehyde or 2-chloro-6-methylquinoline-3-carbaldehyde give, respectively, 1-phenyl-1H-pyrazolo[3,4-b]quinoline, C16H11N3, (III), which crystallizes in the space group Pbcn as a nonmerohedral twin having Z' = 3, or 6-methyl-1-phenyl-1H-pyrazolo[3,4-b]quinoline, C17H13N3, (IV), which crystallizes in the space group R\\overline{3}. The molecules of compound (I) are linked into sheets by a combination of N-H...N and C-H...π(arene) hydrogen bonds, and the molecules of compound (II) are linked by a combination of N-H...N and C-H...π(arene) hydrogen bonds to form a chain of rings. In the structure of compound (III), one of the three independent molecules forms chains generated by C-H...π(arene) hydrogen bonds, with a second type of molecule linked to the chains by a second C-H...π(arene) hydrogen bond and the third type of molecule linked to the chain by multiple π-π stacking interactions. A single C-H...π(arene) hydrogen bond links the molecules of compound (IV) into cyclic centrosymmetric hexamers having \\overline{3} (S6) symmetry, which are themselves linked into a three-dimensional array by π-π stacking interactions. PMID:27585930

  13. Antimalarial effect of agmatine on Plasmodium berghei K173 strain

    Institute of Scientific and Technical Information of China (English)

    SURui-Bin; WEIXiao-Li; LIUYin; LIJin

    2003-01-01

    AIM: To study the antimalarial effect of agmatine (Agm) on chloroquine-susceptible Plasmodium berghei K173strain (S strain) and the P berghei K173 resistant strain (R strain). METHODS: The antimalarial effects of Agm onP berghei K173 S strain and R strain were evaluated by Peters 4-d suppression test in mice. RESULTS: Agm(12.5-200 mg/kg,ig,daily) decreased the parasitemia for both P berghei K173 S strain (IC50=139 mg/kg) and Rstrain (IC50=126mg/kg) in mice. Subcutaneous injection (sc) of Agm (5-40mg/kg,tid) showed relatively strongerantimalarial effect than intragastric gavage (IC50=30 mg/kg) in P berghei K 173 S strain. Spermidine antagonized theantimalarial effect of Agm for P berghei K173 S strain and R strain. Agm did not reverse the chloroquine resistanceof P berghei K173 S strain, dl-α-Difluoromethylornithine (DFMO, sc) decreased the parasitemia of P BergheiK173 S strain and this effect was antagonized by spermidine. CONCLUSION: Agm has an antimalarial effect andthe mechanism is related to its inhibition of polyamine synthesis.

  14. Anti-Malarial Plants of Jonai, India: an Ethnobotanical Approach

    Directory of Open Access Journals (Sweden)

    Tonlong WANGPAN

    2016-03-01

    Full Text Available North-East India represents a unique ecosystem with treasured medicinal plant wealth closely related with Folk medicines. A large number of plants having medicinal properties and their folk uses have remained confined to the natives of this region. The tribal community of Jonai, Assam was explored to expose the indigenous herbal remedy for malaria. Sixteen antimalarial plants belonging to 13 families were reported. The analysis revealed highest fidelity level (FL value for Ajuga integrifolia (100% followed by Ricinus communis (94%, Alstonia scholaris (88%, Oroxylum indicum (86% and Achyranthes aspera (82%. The percentage of respondent’s knowledge (PRK about anti-malarial plants showed Alstonia scholaris as the most commonly known antimalarial species (53% within this region. Preference ranking (PR unveiled eight species to be very effective against malarial parasite, which includes Allium sativum, Artemisia indica, Azadirachta indica, Carica papaya, Clerodendrum glandulosum, Ocimum tenuiflorum, Oroxylum indicum, Piper longum and Piper nigrum. All medicine preparations are made using water as the medium and are orally administered in the form of crude extract, powder, juice and decoction. Overall analysis suggested Ajuga integrifolia, Achyranthes aspera, Alstonia scholaris, Artemisia indica, Oroxylum indicum and Ricinus communis to be used for the development of novel, economical, effective and ecofriendly herbal formulations for healthcare management.

  15. Antimalarials and the fight against malaria in Brazil

    Directory of Open Access Journals (Sweden)

    Luiz MA Carmargo

    2009-04-01

    Full Text Available Luiz MA Carmargo1, Saulo de Oliveira2, Sergio Basano3, Célia RS Garcia21ICBV-USP, Monte Negro, Rondônia, Brasil; 2Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, SP, Brazil; 3CEMETRON, Porto Velho, Guaporé, BrazilAbstract: Malaria, known as the “fevers,” has been treated for over three thousand years in China with extracts of plants of the genus Artemisia (including Artemisia annua, A. opiacea, and A. lancea from which the active compound is artemisin, a sesquiterpene that is highly effective in the treatment of the disease, especially against young forms of the parasite. South American Indians in the seventeenth century already used an extract of the bark of chinchona tree, commonly named “Jesuits’ powder.” Its active compound was isolated in 1820 and its use spread all over the world being used as a prophylactic drug during the construction of the Madeira–Mamoré railroad in the beginning of the twentieth century. During the 1920s to the 1940s, new antimalarial drugs were synthesized to increase the arsenal against this parasite. However, the parasite has presented systematic resistence to conventional antimalarial drugs, driving researchers to find new strategies to treat the disease. In the present review we discuss how Brazil treats Plasmodium-infected patients.Keywords: Plasmodium falciparum, malaria, antimalarials, calcium

  16. In vitro susceptibility of Plasmodium vivax to antimalarials in Colombia.

    Science.gov (United States)

    Fernández, Diana; Segura, César; Arboleda, Margarita; Garavito, Giovanny; Blair, Silvia; Pabón, Adriana

    2014-11-01

    The in vitro susceptibilities of 30 isolates of Plasmodium vivax to a number of antimalarials (chloroquine [CQ], mefloquine, amodiaquine, quinine, and artesunate [AS]) were evaluated. The isolates came from the region of Urabá in Colombia, in which malaria is endemic, and were evaluated by the schizont maturation test. The 50% inhibitory concentration (IC50) was 0.6 nM (95% confidence interval [CI], 0.3 to 1.0 nM) for artesunate, 8.5 nM (95% CI, 5.6 to 13.0 nM) for amodiaquine, 23.3 nM (95% CI, 12.4 to 44.1 nM) for chloroquine, 55.6 nM (95% CI, 36.8 to 84.1 nM) for mefloquine, and 115.3 nM (95% CI, 57.7 to 230.5 nM) for quinine. The isolates were classified according to whether the initial parasites were mature or immature trophozoites (Tfz). It was found that the IC50s for chloroquine and artesunate were significantly different in the two aforementioned groups (P Colombia, P. vivax continues to be susceptible to antimalarials. This is the first report, to our knowledge, showing in vitro susceptibilities of P. vivax isolates to antimalarials in Colombia.

  17. Review of pyronaridine anti-malarial properties and product characteristics

    Directory of Open Access Journals (Sweden)

    Croft Simon L

    2012-08-01

    Full Text Available Abstract Pyronaridine was synthesized in 1970 at the Institute of Chinese Parasitic Disease and has been used in China for over 30 years for the treatment of malaria. Pyronaridine has high potency against Plasmodium falciparum, including chloroquine-resistant strains. Studies in various animal models have shown pyronaridine to be effective against strains resistant to other anti-malarials, including chloroquine. Resistance to pyronaridine appears to emerge slowly and is further retarded when pyronaridine is used in combination with other anti-malarials, in particular, artesunate. Pyronaridine toxicity is generally less than that of chloroquine, though evidence of embryotoxicity in rodents suggests use with caution in pregnancy. Clinical pharmacokinetic data for pyronaridine indicates an elimination T1/2 of 13.2 and 9.6 days, respectively, in adults and children with acute uncomplicated falciparum and vivax malaria in artemisinin-combination therapy. Clinical data for mono or combined pyronaridine therapy show excellent anti-malarial effects against P. falciparum and studies of combination therapy also show promise against Plasmodium vivax. Pyronaridine has been developed as a fixed dose combination therapy, in a 3:1 ratio, with artesunate for the treatment of acute uncomplicated P. falciparum malaria and blood stage P. vivax malaria with the name of Pyramax® and has received Positive Opinion by European Medicines Agency under the Article 58 procedure.

  18. Synthesis of 2-phenyl- and 2,3-diphenyl-quinolin-4-carboxylic acid derivatives

    International Nuclear Information System (INIS)

    Quinolin derivatives are a group of compounds known to possess a wide range of biological activities. The chemistry of quinolines together with their corresponding aldehydes were dealt with in chapter one of this study. Special emphasis was given to the chemistry of benzaldehyde. Twenty five 2-phenyl- and 2,3-diphenyl-quinolin-4-carboxylic acid derivatives together with their corresponding intermediates were prepared in this work. Basically, the synthetic design of these compounds arise from the appropriate disconnections of the target 2-phenyl and 2,3-diphenyl-quinolin-4-carboxylic acids. The retro synthesis analysis of these compounds reveals pyruvic acid, aromatic amine and benzaldehyde or phenyl pyruvic acid, aromatic amine and benzaldehyde as possible logical precursors for 2-phenyl-and 2,3-diphenyl- quinoline-4-carboxylic acids respectively. The purity and identities of the synthesized compounds were elucidated through chromatographic and spectroscopic techniques. The compounds were heavily subjected to spectroscopic analysis (UV, IR, GC/MS, 1H-and 13C- NMR). The appropriate disconnections and the mechanisms of the corresponding reactions were given and discussed in chapter three. The spectral data were interpreted and correlated with the target structures. The prepared 2-phenyl- and 2,3-diphenyl-quinoline-4-carboxylic acid derivatives were screened for their antibacterial activity. The compounds were tested against the standard bacterial organisms B. subtilis, S. aureus, E. coli and P. vulgaris. Some of these compounds were devoid of antibacterial activity against S. aureus and P. vulgaris, while others showed moderate activity. All of the tested compounds showed an activity against B. subtilis and E. coli. 2,3-diphenyl -6-sulphanilamide-quinolin-4-carboxylic acid showed the highest activity against the four standard tested organisms.(Author)

  19. Antimalarial activity and toxicity of Garcinia mangostana Linn.

    Institute of Scientific and Technical Information of China (English)

    Ratchanu; Bunyong; Wanna; Chaijaroenkul; Tullayakorn; Plengsuriyakarn; Kesara; Na-Bangchang

    2014-01-01

    Objective:To investigate the antimalarial activity and toxicity of the crude ethanolic extract of its pericarp both in vitro and in vim.Methods:The antimalarial activity of Gareinja mangostana(G.mangostana)Linn.extract against 3D7 and Kl Plasmodium falciparum(P.falciparum)clone were assessed using SYBR green I-based assay.A 4-day suppressive test of Plasmodium berghei{P.berghei)infected mouse was performed to investigate in vivo antimalarial activity.Results:The in vitro antimalarial activity was seleclive(SI>5?and classified as weak and good lo moderate activity against both 3D7 and K1 P.falciparum,clones with median IC50(range)values of 11.12(10.94-11.29)and 7.54(6.80-7.68)μg/mL,respectively.The extract was considered nontoxic to mice.The maximum tolerated doses for acute and subacute toxicity in mice were 5 000and 2 000 mg/kg,respectively.Median(range)parasite density on day 4 of the negative control group(25%Tween-80),mice treated with 250,500,1000,and 2 000 mg/kg body weight of the extract,and 10 mg/kg body weight of chloroquine for 14 d were 12.8(12.2-13.7),11.4(9.49-13.8),11.6(9.9-12.5),11.7(10.6-12.8),10.9(9.4-11.6)and 0(0-0)%respectively.Parasite density on day 4in the control group treated with Tween-80 was higher than the groups treated with chloroquine and all dose levels of the extract.Conclusions:G.mangostana linn,showed weak antimalarial activity of the extract both in vitro and in vivo could be due to limitation of absorption of the active compounds.

  20. Methylnaltrexone bromide methanol monosolvate

    Directory of Open Access Journals (Sweden)

    Xinbo Zhou

    2012-03-01

    Full Text Available In the title compound [systematic name: (4R,4aS,7aR,12bS-3-cyclopropylmethyl-4a,9-hydroxy-7-oxo-2,3,4,4a,5,6,7,7a-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-3-ium bromide methanol monosolvate], C21H26NO4+·Br−·CH3OH, two of the three six-membered rings adopt chair conformations while the third, which contains a C=C double bond, adopts an approximate half-boat conformation. The 2,3-dihydrofuran ring adopts an envelope conformation. In the crystal, the components are linked by O—H...O and O—H...Br hydrogen bonds. The absolute stereochemistry was inferred from one of the starting materials.

  1. Methanol synthesis beyond chemical equilibrium

    NARCIS (Netherlands)

    van Bennekom, J. G.; Venderbosch, R. H.; Winkelman, J. G. M.; Wilbers, E.; Assink, D.; Lemmens, K. P. J.; Heeres, H. J.

    2013-01-01

    In commercial methanol production from syngas, the conversion is thermodynamically limited to 0.3-0.7 leading to large recycles of non-converted syngas. This problem can be overcome to a significant extent by in situ condensation of methanol during its synthesis which is possible nowadays due to the

  2. Methanol as an energy carrier

    Energy Technology Data Exchange (ETDEWEB)

    Biedermann, P.; Grube, T.; Hoehlein, B. (eds.)

    2006-07-01

    For the future, a strongly growing energy demand is expected in the transport sector worldwide. Economically efficient oil production will run through a maximum in the next decade. Higher fuel prices and an environmentally desirable reduction of emissions will increase the pressure for reducing fuel consumption and emissions in road traffic. These criteria show the urgent necessity of structural changes in the fuel market. Due to its advantages concerning industrial-scale production, storage and global availability, methanol has the short- to medium-term potential for gaining increased significance as a substitution product in the energy market. Methanol can be produced both from fossil energy sources and from biomass or waste materials through the process steps of synthesis gas generation with subsequent methanol synthesis. Methanol has the potential to be used in an environmentally friendly manner in gasoline/methanol mixtures for flexible fuel vehicles with internal combustion engines and in diesel engines with pure methanol. Furthermore, it can be used in fuel cell vehicles with on-board hydrogen production in direct methanol fuel cell drives, and in stationary systems for electricity and heat generation as well as for hydrogen production. Finally, in portable applications it serves as an energy carrier for electric power generation. In this book, the processes for the production and use of methanol are presented and evaluated, markets and future options are discussed and issues of safety and environmental impacts are addressed by a team of well-known authors. (orig.)

  3. Mineralization of Quinoline by BDD Anodes: Variable Effects and Its Effluent Characteristics

    Directory of Open Access Journals (Sweden)

    C. R. Wang

    2015-01-01

    Full Text Available BDD anodes were selected for quinoline mineralization and influence of operating parameters, such as current density, initial quinoline concentration, supporting electrolyte, and initial pH was investigated. Based on the consideration of quinoline removal efficiency and average current efficiency, at initial quinoline concentration of 50 mg L−1 and pH of 7, the optimal condition was confirmed as current density of 75 mA cm−2, electrolysis time of 1.5 h, and Na2SO4 concentration of 0.05 mol L−1 by orthogonal test. At different electrolysis time, its effluent characteristics were focused on. The biodegradability (the ratio between BOD5 and COD was enhanced from initial 0.02 to 0.57 at 90 min. The specific oxygen uptake rate was used to assess effluent toxicity, and the value gradually reduced with decreasing effluent organic concentration with mean value of 5.51, 4.19, and 2.20 mgO2 g−1MLSS at electrolysis time of 15, 30, and 45 min, respectively. Compared with control sample (prepared with glucose, the effluent of quinoline mineralization showed obvious inhibition effect on microorganisms at electrolysis time of 15 min, and then it was significantly faded at 30 min and 45 min.

  4. Regioselective demethylation of quinoline derivatives. A DFT rationalization

    Science.gov (United States)

    Belferdi, Fatiha; Merabet, Naima; Belkhiri, Lotfi; Douara, Bachir

    2016-08-01

    Demethylation of compound 2,7-dimethoxyquinoline-3-carbaldehyde 1, is carried out using BBr3. However, all attempts led, either to the starting material or to the regioselective demethylation at position 2 affording the product 4a. The nature (donor or acceptor) and the position of the R (CHO or CN) group is likely to play a role in the preventing the demethylation at position 7. To address this phenomena, the demethylation of 2-chloro-7-methoxyquinoline-3-carbaldehyde 2 and 2,7-dimethoxyquinoline-3-carbaldehyde 3 has been carried out. To support the results obtained, theoretical computations at DFT level (vide infra) have been carried out upon compound 1. The exploration of how the gas-phase demethylation process on Quinoline can be affected at a position 7 center by stepwise substation effects using different electro-donor and attractor groups, show that demethylation process seems to be more favorable when substituent is an electro-donor. This is sustained by bond energy and thermodynamic analyses (vide infra).

  5. Zero Kinetic Energy Photoelectron Spectroscopy of Benzo[h]quinoline.

    Science.gov (United States)

    Harthcock, Colin; Zhang, Jie; Kong, Wei

    2015-12-17

    We report zero kinetic energy (ZEKE) photoelectron spectroscopy of benzo[h]quinoline (BhQ) via resonantly enhanced multiphoton ionization (REMPI) through the first electronically excited state S1. From the simulated REMPI spectra with and without Herzberg-Teller coupling, we conclude that vibronic coupling plays a minor but observable role in the electronic excitation to the S1 state. We further compare the S1 state of BhQ with the first two electronically excited states of phenanthrene, noticing a similarity of the S1 state of BhQ with the second electronically excited state S2 of phenanthrene. In the ZEKE spectra of BhQ, the vibrational frequencies of the cationic state D0 are consistently higher than those of the intermediate neutral state, indicating enhanced bonding upon ionization. The sparse ZEKE spectra, compared with the spectrum of phenanthrene containing rich vibronic activities, further imply that the nitrogen atom has attenuated the structural change between S1 and D0 states. We speculate that the nitrogen atom can withdraw an electron in the S1 state and donate an electron in the D0 state, thereby minimizing the structural change during ionization. The origin of the first electronically excited state is determined to be 29,410 ± 5 cm(-1), and the adiabatic ionization potential is determined to be 65,064 ± 7 cm(-1). PMID:26039927

  6. Characterization of Strain Pseudomonas sp.Q1 in Microbial Fuel Cell for Treatment of Quinoline-Contaminated Water

    Institute of Scientific and Technical Information of China (English)

    ZHANG Cui-Ping; CHEN Shan-Shan; LIU Guang-Li; ZHANG Ren-Duo; XIE Jian

    2012-01-01

    To find new strain in the microbial fuel cell (MFC) for quinoline removal from wastewater and soil,a facultative anaerobic bacterium strain was isolated from the anode of MFC,utilizing quinoline as the carbon source and electron donor.Based on the 16S rRNA sequence analysis,the bacterium strain was Gram-negative and identified as Pseudomonas sp.Q1 according to its morphology and physiochemical properties.The strain was inoculated into a double-chambered MFC using various quinoline concentratious (0,50,75,86,100,150,200 and 300 mg L-1) combining with 300 mg L-1 glucose as the fuel.Results showed that electricity was generated from the MFC,in which quinoline was degraded simultaneously.The values of Coulombic efficiency (CE) increased with the increase of quinoline concentrations from 0 to 100 mg L-1 then decreased with the increase of quinoline concentration from 100 to 300 mg L-1,and the maximum CE 36.7% was obtained at the quinoline concentration of 100 mg L-1.The cyclic voltammetry analysis suggested that the mechanism of electron transfer was through excreting mediators produced by the strain Q1.The MFC should be a potential method for the treatment of quinoline-contaminated water and soil.

  7. Analytical sample preparation strategies for the determination of antimalarial drugs in human whole blood, plasma and urine

    DEFF Research Database (Denmark)

    Casas, Monica Escolà; Hansen, Martin; Krogh, Kristine A;

    2014-01-01

    Antimalarial drugs commonly referred to as antimalarials, include a variety of compounds with different physicochemical properties. There is a lack of information on antimalarial distribution in the body over time after administration, e.g. the drug concentrations in whole blood, plasma, and urine...... summarized. Finally, the main problems that the researchers have dealt with are highlighted. This information will aid analytical chemists in the development of novel methods for determining existing antimalarials and upcoming new drugs....

  8. When Indolizine Meets Quinoline: Diversity-Oriented Synthesis of New Polyheterocycles and Their Optical Properties.

    Science.gov (United States)

    Park, Sujin; Kwon, Dah In; Lee, Jeeyeon; Kim, Ikyon

    2015-08-10

    Fluorescence-based technologies play a pivotal role in various biomedical applications. Here we report an efficient route to a new class of fluorophores, indolizino[3,2-c]quinolines, via the oxidative Pictet-Spengler cyclization strategy. The condensation of several 2-methylpyridines with 2-bromo-2'-nitroacetophenone allowed for the rapid assembly of indolizines with a 2-nitrophenyl group at the C2 position. The subsequent reduction of the nitro group under mild conditions followed by oxidative Pictet-Spengler cyclization with various aryl aldehydes in the presence of a catalytic amount of FeCl3 furnished the indolizino[3,2-c]quinolines in good overall yields. We also examined the photophysical properties of this new series of polyheterocyclic compounds. Several indolizino[3,2-c]quinolines were found to have unique and desirable optical properties, suggesting that these compounds may be suitable for use as prospective fluorescent probes in aqueous systems. PMID:26203781

  9. Chemical consequences of pyrazole orientation in Ru(II) complexes of unsymmetric quinoline-pyrazole ligands.

    Science.gov (United States)

    Hedberg Wallenstein, Joachim; Fredin, Lisa A; Jarenmark, Martin; Abrahamsson, Maria; Persson, Petter

    2016-08-01

    A series of homoleptic Ru(II) complexes including the tris-bidentate complexes of a new bidentate ligand 8-(1-pyrazol)-quinoline (Q1Pz) and bidentate 8-(3-pyrazol)-quinoline (Q3PzH), as well as the bis-tridentate complex of bis(quinolinyl)-1,3-pyrazole (DQPz) was studied. Together these complexes explore the orientation of the pyrazole relative to the quinoline. By examining the complexes structurally, photophysically, photochemically, electrochemically, and computationally by DFT and TD-DFT, it is shown that the pyrazole orientation has a significant influence on key properties. In particular, its orientation has noticeable effects on oxidation and reduction potentials, photostability and proton sensitivity, indicating that [Ru(Q3PzH)3](2+) is a particularly good local environment acidity-probe candidate. PMID:27240703

  10. Anion- interactions in layered structures of salts of 5-(hydroxyimino) quinolin-8-one and related salts

    Indian Academy of Sciences (India)

    Prithiviraj Khakhlary; Jubaraj B Baruah

    2015-01-01

    Relevance of anion- interactions in chloride, bromide, nitrate and perchlorate salts of 5-(hydroxyimino)quinolin-8-one are discussed. Structures of nitrate salt of 5-aminoquinoline as well as nitrate salt of 4-hydroxyquinazoline are compared with the structure of nitrate salt of 5-(hydroxyimino)quinolin-8-one. From such a comparison, two different arrangements of nitrate ions with respect to the respective cations are discerned. Nitrate ions are sandwiched between aromatic planes of cations in nitrate salts of 5-(hydroxyimino)quinolin-8-one or 4-hydroxyquinazoline; whereas, nitrate ions are in oblique positions with respect to aromatic planes of counter cations in nitrate salt of 5-aminoquinoline. Binding constants of different nitrate salts in solution are determined by UV-visible spectroscopic titrations. Solution study shows formation of ion-pairs of these salts in solution.

  11. Crystallization and preliminary X-ray crystallographic analysis of human quinolinate phosphoribosyltransferase

    International Nuclear Information System (INIS)

    H. sapiens quinolinate phosphoribosyltransferase has been expressed, purified and crystallized. A diffraction data set has been collected and processed at 2.8 Å resolution. Quinolinate phosphoribosyltransferase (QPRTase) is a key NAD-biosynthetic enzyme which catalyzes the transfer of quinolinic acid to 5-phosphoribosyl-1-pyrophosphate, yielding nicotinic acid mononucleotide. Homo sapiens QPRTase (Hs-QPRTase) appeared as a hexamer during purification and the protein was crystallized. Diffraction data were collected and processed at 2.8 Å resolution. Native Hs-QPRTase crystals belonged to space group P21, with unit-cell parameters a = 76.2, b = 137.1, c = 92.7 Å, β = 103.8°. Assuming the presence of six molecules in the asymmetric unit, the calculated Matthews coefficient is 2.46 Å3 Da−1, which corresponds to a solvent content of 49.9%

  12. Novel quinolines carrying pyridine, thienopyridine, isoquinoline, thiazolidine, thiazole and thiophene moieties as potential anticancer agents.

    Science.gov (United States)

    Ghorab, Mostafa M; Alsaid, Mansour S; Al-Dosari, Mohammed S; Ragab, Fatma A; Al-Mishari, Abdullah A; Almoqbil, Abdulaziz N

    2016-06-01

    As a part of ongoing studies in developing new anticancer agents, novel 1,2-dihydropyridine 4, thienopyridine 5, isoquinolines 6-20, acrylamide 21, thiazolidine 22, thiazoles 23-29 and thiophenes 33-35 bearing a biologically active quinoline nucleus were synthesized. The structure of newly synthesized compounds was confirmed on the basis of elemental analyses and spectral data. All the newly synthesized compounds were evaluated for their cytotoxic activity against the breast cancer cell line MCF7. 2,3-Dihydrothiazole-5-carboxamides 27, 25, 4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (34), 1,2-dihydroisoquinoline-7-carbonitrile (7), 5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide (35), 1,2-dihydroisoquinoline-7-carbonitrile (6), 2-cyano-3-(dimethylamino)-N-(quinolin-3-yl)acrylamide (21), 1,2-dihydroisoquinoline-7-carbonitriles (11) and (8) exhibited higher activity (IC50 values of 27-45 μmol L-1) compared to doxorubicin (IC50 47.9 μmol L-1). LQ quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (12), 2-thioxo-2,3-dihydrothiazole-5-carboxamide (28) and quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (15) show activity comparable to doxorubicin, while (quinolin-3-yl)-1,2-dihydroisoquinoline-7-carbonitrile (9), 2,3-dihydrothiazole-5-carboxamide (24), thieno [3,4-c] pyridine-4(5H)-one (5), cyclopenta[b]thiophene-3-carboxamide (33) and (quinolin-3-yl)-6-stryl-1,2-dihydroisoquinoline-7-carbonitrile (10) exhibited moderate activity, lower than doxorubicin. PMID:27279061

  13. Novel quinolines carrying pyridine, thienopyridine, isoquinoline, thiazolidine, thiazole and thiophene moieties as potential anticancer agents

    Directory of Open Access Journals (Sweden)

    Ghorab Mostafa M.

    2016-06-01

    Full Text Available As a part of ongoing studies in developing new anticancer agents, novel 1,2-dihydropyridine 4, thienopyridine 5, isoquinolines 6–20, acrylamide 21, thiazolidine 22, thiazoles 23–29 and thiophenes 33–35 bearing a biologically active quinoline nucleus were synthesized. The structure of newly synthesized compounds was confirmed on the basis of elemental analyses and spectral data. All the newly synthesized compounds were evaluated for their cytotoxic activity against the breast cancer cell line MCF7. 2,3-Dihydrothiazole-5-carboxamides 27, 25, 4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (34, 1,2-dihydroisoquinoline-7-carbonitrile (7, 5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxamide (35, 1,2-dihydroisoquinoline-7-carbonitrile (6, 2-cyano-3-(dimethylamino-N-(quinolin-3-ylacrylamide (21, 1,2-dihydroisoquinoline-7-carbonitriles (11 and (8 exhibited higher activity (IC50 values of 27–45 μmol L–1 compared to doxorubicin (IC50 47.9 μmol L–1. LQ quinolin-3-yl-1,2-dihydroisoquinoline-7-carbonitrile (12, 2-thioxo-2,3-dihydrothiazole-5-carboxamide (28 and quinolin-3-yl-1,2-dihydroisoquinoline-7-carbonitrile (15 show activity comparable to doxorubicin, while (quinolin-3-yl-1,2-dihydroisoquinoline-7-carbonitrile (9, 2,3-dihydrothiazole-5-carboxamide (24, thieno [3,4-c] pyridine-4(5H-one (5, cyclopenta[b]thiophene-3-carboxamide (33 and (quinolin-3-yl-6-stryl-1,2-dihydroisoquinoline-7-carbonitrile (10 exhibited moderate activity, lower than doxorubicin.

  14. Antimalarial Benzoxaboroles Target Plasmodium falciparum Leucyl-tRNA Synthetase.

    Science.gov (United States)

    Sonoiki, Ebere; Palencia, Andres; Guo, Denghui; Ahyong, Vida; Dong, Chen; Li, Xianfeng; Hernandez, Vincent S; Zhang, Yong-Kang; Choi, Wai; Gut, Jiri; Legac, Jennifer; Cooper, Roland; Alley, M R K; Freund, Yvonne R; DeRisi, Joseph; Cusack, Stephen; Rosenthal, Philip J

    2016-08-01

    There is a need for new antimalarials, ideally with novel mechanisms of action. Benzoxaboroles have been shown to be active against bacteria, fungi, and trypanosomes. Therefore, we investigated the antimalarial activity and mechanism of action of 3-aminomethyl benzoxaboroles against Plasmodium falciparum Two 3-aminomethyl compounds, AN6426 and AN8432, demonstrated good potency against cultured multidrug-resistant (W2 strain) P. falciparum (50% inhibitory concentration [IC50] of 310 nM and 490 nM, respectively) and efficacy against murine Plasmodium berghei infection when administered orally once daily for 4 days (90% effective dose [ED90], 7.4 and 16.2 mg/kg of body weight, respectively). To characterize mechanisms of action, we selected parasites with decreased drug sensitivity by culturing with stepwise increases in concentration of AN6426. Resistant clones were characterized by whole-genome sequencing. Three generations of resistant parasites had polymorphisms in the predicted editing domain of the gene encoding a P. falciparum leucyl-tRNA synthetase (LeuRS; PF3D7_0622800) and in another gene (PF3D7_1218100), which encodes a protein of unknown function. Solution of the structure of the P. falciparum LeuRS editing domain suggested key roles for mutated residues in LeuRS editing. Short incubations with AN6426 and AN8432, unlike artemisinin, caused dose-dependent inhibition of [(14)C]leucine incorporation by cultured wild-type, but not resistant, parasites. The growth of resistant, but not wild-type, parasites was impaired in the presence of the unnatural amino acid norvaline, consistent with a loss of LeuRS editing activity in resistant parasites. In summary, the benzoxaboroles AN6426 and AN8432 offer effective antimalarial activity and act, at least in part, against a novel target, the editing domain of P. falciparum LeuRS.

  15. Antimalarial activity of Malaysian Plectranthus amboinicus against Plasmodium berghei

    Directory of Open Access Journals (Sweden)

    Norazsida Ramli

    2014-01-01

    Full Text Available Context: Malaria is a mosquito-borne disease caused by parasitic protozoa from the genus of Plasmodium. The protozoans have developed resistance against many of current drugs. It is urgent to find an alternative source of new antimalarial agent. In the effort to discover new antimalarial agents, this research has been conducted on Plectranthus amboinicus. Aims: This study was conducted to evaluate the toxicity and antiplasmodial properties of P. amboinicus. Materials and Methods: Acute oral toxicity dose at 5000 mg/kg was conducted to evaluate the safety of this extract. Twenty mice were divided into control and experimental group. All the mice were observed for signs of toxicity, mortality, weight changes and histopathological changes. Antimalarial activity of different extract doses of 50, 200, 400 and 1000 mg/kg were tested in vivo against Plasmodium berghei infections in mice (five mice for each group during early, established and residual infections. Results: The acute oral toxicity test revealed that no mortality or evidence of adverse effects was seen in the treated mice. The extract significantly reduced the parasitemia by the 50 (P = 0.000, 200 (P = 0.000 and 400 mg/kg doses (P = 0.000 in the in vivo prophylactic assay. The percentage chemo-suppression was calculated as 83.33% for 50 mg/kg dose, 75.62% for 200 mg/kg dose and 90.74% for 400 mg/kg dose. Body weight of all treated groups; T1, T2, T3 and T4 also showed enhancement after 7 days posttreatment. Statistically no reduction of parasitemia calculated for curative and suppressive test. Conclusion: Thus, this extract may give a promising agent to be used as a prophylactic agent of P. berghei infection.

  16. Lanthanide perchlorate complexes of quinoline-1-oxide and isoquinoline-2-oxide

    OpenAIRE

    Kalyanasundaram, R; Navaneetham, NS; Soundararajan, S.

    1985-01-01

    Complexes of lanthanide perchlorates with quinoline-1-oxide and isoquinoline-2-oxide have been isolated for the first time characterised by analysis, conductance and IR, NMR and electronic spectoral studies. The complexes of quinoline-1-oxide have the composition $Ln(QNO)_8$$(ClO_4)_3$ where Ln = La, Pr or Nd and $Ln(QNO)_7$ where Ln = Gd, Dy, Ho, Er, Yb. The isoquinoline-2-oxide complexes analyse for the formula $Ln(IsoQNO)_7(ClO_4)_3$ where Ln = La-Yb.

  17. Lowest energy vibrational modes of some naphthalene derivatives: Azulene, quinoline, isoquinoline - Experiment and theory

    Science.gov (United States)

    Martin-Drumel, M. A.; Pirali, O.; Loquais, Y.; Falvo, C.; Bréchignac, Ph.

    2013-02-01

    Far infrared (FIR) gas phase absorption spectra of azulene, quinoline and isoquinoline have been recorded using a Fourier transform Bruker IFS125 interferometer at medium resolution (0.5 cm-1). Assignments of these weak vibrational bands were performed using density-functional theory calculations carried out at the harmonic and anharmonic levels. Agreement between observed and calculated band positions is better than 5% for azulene and 1% for quinoline and isoquinoline. The relative band intensities are also correctly predicted. Molecular structure dependence of the FIR spectra is discussed based on the comparative study of three selected FIR modes.

  18. Synthesis and in vitro antioxidant activity of quinolin-5-ylamine derivatives

    Directory of Open Access Journals (Sweden)

    L. Mallesha

    2013-07-01

    Full Text Available Imines of six new quinolin-5-ylamine derivatives 3(a-c and 5(a-c were synthesized by the reaction of quinolin-5-ylamine (1 with different aldehydes 2(a-c and ketones 4(a-c. The chemical structures of the compounds were confirmed by UV-visible, FT-IR and 1H NMR spectral study. New compounds were screened for the antioxidant activity by DPPH (2,2-diphenyl-1-picrylhydrazyl method. Butylated Hydroxytoluene (BHT was used as standard. All the compounds showed DPPH radical scavenging activity, where compound 3c was the best radical scavenger.

  19. Synthesis and in vitro antioxidant activity of quinolin-5-ylamine derivatives

    OpenAIRE

    Mallesha, L.; B. K. Kendagannaswamy; K. N. Mohana

    2013-01-01

    Imines of six new quinolin-5-ylamine derivatives 3(a-c) and 5(a-c) were synthesized by the reaction of quinolin-5-ylamine (1) with different aldehydes 2(a-c) and ketones 4(a-c). The chemical structures of the compounds were confirmed by UV-visible, FT-IR and 1H NMR spectral study. New compounds were screened for the antioxidant activity by DPPH (2,2-diphenyl-1-picrylhydrazyl) method. Butylated Hydroxytoluene (BHT) was used as standard. All the compounds showed DPPH radical scavenging activity...

  20. Mono- and bis-thiazolium salts have potent antimalarial activity.

    Science.gov (United States)

    Hamzé, Abdallah; Rubi, Eric; Arnal, Pascal; Boisbrun, Michel; Carcel, Carole; Salom-Roig, Xavier; Maynadier, Marjorie; Wein, Sharon; Vial, Henri; Calas, Michèle

    2005-05-19

    Three new series comprising 24 novel cationic choline analogues and consisting of mono- or bis (N or C-5-duplicated) thiazolium salts have been synthesized. Bis-thiazolium salts showed potent antimalarial activity (much superior to monothiazoliums). Among them, bis-thiazolium salts 12 and 13 exhibited IC(50) values of 2.25 nM and 0.65 nM, respectively, against P. falciparum in vitro. These compounds also demonstrated good in vivo activity (ED(50)

  1. Substandard anti-malarial drugs in Burkina Faso

    Directory of Open Access Journals (Sweden)

    Sie Ali

    2008-05-01

    Full Text Available Abstract Background There is concern about an increasing infiltration of markets by substandard and fake medications against life-threatening diseases in developing countries. This is particularly worrying with regard to the increasing resistance development of Plasmodium falciparum against affordable anti-malarial medications, which has led to a change to more expensive drugs in most endemic countries. Methods A representative sample of modern anti-malarial medications from licensed (public and private pharmacies, community health workers and illicit (market and street vendors, shops sources has been collected in the Nouna Health District in north-western Burkina Faso in 2006. All drugs were tested for their quality with the standard procedures of the German Pharma Health Fund-Minilab. Detected low standard drugs were re-tested with European Pharmacopoeia 2.9.1 standards for disintegration and ultraviolet-visible spectroscopy at the laboratory of the Heidelberg University for confirmation. Results Overall, 86 anti-malarial drug samples were collected, of which 77 samples have been included in the final analysis. The sample consisted of 39/77 (50% chloroquine, 10/77 (13% pyrimethamine-sulphadoxine, 9/77 (12% quinine, 6/77 (8% amodiaquine, 9/77 (12% artesunate, and 4/77 (5% artemether-lumefantrine. 32/77 (42% drug samples were found to be of poor quality, of which 28 samples failed the visual inspection, nine samples had substandard concentrations of the active ingredient, four samples showed poor disintegration, and one sample contained non of the stated active ingredient. The licensed and the illicit market contributed 5/47 (10.6% and 27/30 (90.0% samples of substandard drugs respectively. Conclusion These findings provide further evidence for the wide-spread existence of substandard anti-malarial medications in Africa and call for strengthening of the regulatory and quality control capacity of affected countries, particularly in view of the

  2. Home treatment of febrile children with antimalarial drugs in Togo.

    OpenAIRE

    Deming, M. S.; Gayibor, A.; Murphy, K; Jones, T. S.; Karsa, T.

    1989-01-01

    In Togo, the principal strategy for preventing death from malaria in children is prompt treatment of fever with antimalarial drugs. A household survey was conducted in a rural area of south-central Togo in which information was collected from mothers on the treatment received by 507 children under 5 years of age who, according to their mothers, had recently had fever. Altogether, 20% of the children (95% confidence interval (Cl): 15-25%) were seen at a health centre during their illness, whil...

  3. Proteomics analysis of antimalarial targets of Garcinia mangostana Linn.

    OpenAIRE

    Wanna Chaijaroenkul; Artitiya Thiengsusuk; Kanchana Rungsihirunrat; Stephen Andrew Ward; Kesara Na-Bangchang

    2014-01-01

    Objective: To investigate possible protein targets for antimalarial activity of Garcinia mangostana Linn. (G. mangostana) (pericarp) in 3D7 Plasmodium falciparum clone using 2-dimensional electrophoresis and liquid chromatography mass-spectrometry (LC/MS/MS). Methods: 3D7 Plasmodium falciparum was exposed to the crude ethanolic extract of G. mangostana Linn. (pericarp) at the concentrations of 12μg/mL (IC50 level: concentration that inhibits parasite growth by 50%) and 30 μg/mL (IC90 level...

  4. Targeting Plasmodium falciparum Hsp90: Towards Reversing Antimalarial Resistance

    Directory of Open Access Journals (Sweden)

    Dea Shahinas

    2013-02-01

    Full Text Available Malaria continues to exact a great human toll in tropical settings. Antimalarial resistance is rife and the parasite inexorably develops mechanisms to outwit our best drugs, including the now first-line choice, artesunate. Novel strategies to circumvent resistance are needed. Here we detail drug development focusing on heat shock protein 90 and its central role as a chaperone. A growing body of evidence supports the role for Hsp90 inhibitors as adjunctive drugs able to restore susceptibility to traditionally efficacious compounds like chloroquine.

  5. Vibronic Spectroscopy of a Structural Isomer of Quinoline: -

    Science.gov (United States)

    Mehta-Hurt, Deepali N.; Korn, Joseph A.; Zwier, Timothy S.

    2013-06-01

    This talk will present results of a gas phase, jet-cooled vibronic spectroscopy study of (Z)-phenylvinylnitrile ((Z)-C_6H_5-CH=CH-C=N, (Z)-PVN). With a substituent locked into a cis conformation with respect to the aromatic ring, (Z)-PVN is postulated to be a molecule with an ideal functionality to isomerize to quinoline upon photoexcitation. As such, (Z)-PVN is particularly relevant to Titan's nitrile-containing atmosphere, where much of the chemistry is photochemically driven. As a first step towards such photochemical studies, a fluorescence excitation spectrum of a mixture of (E)- and (Z)-PVN was collected spanning the range 33,300-35,580 cm^{-1} (300.0-281.0 nm). Previous investigations in the Zwier group pertaining to the vibronic spectroscopy of (E)-PVN allowed for the identification of peaks in the (E)- and (Z)-PVN composite spectrum that were solely due to (Z)-PVN, and the S_0-S_1 origin of (Z)-PVN was identified as a dominant band that occurs at 33,706 cm^{-1}. For additional confirmation, ultraviolet depletion spectroscopy (UVD) was used to obtain an isomer specific spectrum of (Z)-PVN as well as search for non-radiative transitions. Dispersed fluorescence spectra that characterize the vibronic activity have also been acquired. A comparison between the vibronic spectroscopy of (Z)-PVN with both (E)-PVN and (Z)-phenylvinylacetylene ((Z)-PVA), the hydrocarbon analog of (Z)-PVN, will be made in this talk.

  6. Acute methanol toxicity in minipigs

    Energy Technology Data Exchange (ETDEWEB)

    Dorman, D.C.; Dye, J.A.; Nassise, M.P.; Ekuta, J.; Bolon, B.

    1993-01-01

    The pig has been proposed as a potential animal model for methanol-induced neuro-ocular toxicosis in humans because of its low liver tetrahydrofolate levels and slower rate of formate metabolism compared to those of humans. To examine the validity of this animal model, 12 4-month-old female minipigs (minipig YU) were given a single oral dose of water or methanol at 1.0, 2.5, or 5.0 g/kg body wt by gavage (n = 3 pigs/dose). Dose-dependent signs of acute methanol intoxication, which included mild CNS depression, tremors, ataxia, and recumbency, developed within 0.5 to 2.0 hr, and resolved by 52 hr. Methanol- and formate-dosed pigs did not develop optic nerve lesions, toxicologically significant formate accumulation, or metabolic acidosis. Based on results following a single dose, female minipigs do not appear to be overtly sensitive to methanol and thus may not be a suitable animal model for acute methanol-induced neuroocular toxicosis.

  7. The role of antimalarial treatment in the elimination of malaria.

    Science.gov (United States)

    Gosling, R D; Okell, L; Mosha, J; Chandramohan, D

    2011-11-01

    With declining transmission of malaria in several regions of the world and renewed interest in the elimination of malaria, strategies for malaria control using antimalarial drugs are being revisited. Drug-based strategies to reduce transmission of malaria need to target the asymptomatic carriers of infection. Drugs that are effective against gametocytes are few in number, but it may be possible to reduce gametocyte production by killing the asexual stages, for which more drugs are available. Drugs for use in large-scale programmes must be safe and tolerable. Strategies include improving access to treatment for malaria with an efficacious drug, intermittent-treatment programmes, and mass drug administration, with and without screening for malaria. Recent proposals have targeted high-risk groups for interventions. None of the strategies has been rigorously tested with appropriate control groups for comparison. Because of the lack of field evidence, modelling has been used. Models have shown, first, that for long-lasting effects, drug administration programmes should be linked with vector control, and second, that if elimination is the aim, programmes are likely to be more successful when applied to smaller populations of a few thousand or less. In order to sustain the gains following the scaling up of vector control and use of artemisinin combination therapies (ACTs), strategies that use antimalarials effectively need to be devised and evidence generated for the most cost-efficient way forward.

  8. Proteomics analysis of antimalarial targets of Garcinia mangostana Linn.

    Institute of Scientific and Technical Information of China (English)

    Wanna; Chaijaroenkul; Artitiya; Thiengsusuk; Kanchana; Rungsihirunrat; Stephen; Andrew; Ward; Kesara; Na-Bangchang

    2014-01-01

    Objective:To investigate possible protein targets for antimalarial activity of Garcina mangostana Linn.(G.mangostana)(pericarp)in 3D7 Plasmodium falciparum clone using 2-dimensional electrophoresis and liquid chromatography mass-spectrometry(LC/MS/MS).Methods:3D7 Plasmodium falciparum was exposed to the crude ethanolic extract of G.mangostana Linn.(pericarp)at the concentrations of 12μg/mL(1C50level:concentration that inhibits parasite growth by 50%)and 30μg/mL(1C90level:concentration that inhibits parasite growth by 90%)for 12 h.Parasite proteins were separated by 2-dimensional electrophoresis and identified by LC/MS/MS.Results:At the IC50concentration,about 82%of the expressed parasite proteins were matched with the control(non-exposed),while at the IC90concentration,only 15%matched proteins were found.The selected protein spots from parasite exposed to the plant extract at the concentration of 12μg/mL were identified as eneymes that play role in glycolysis pathway,i.e.,phosphoglyeerate mutase putative,L-lactate dehydrogenase/glyceraldehyde-3-phosphate dehydrogenase,and fruetose-bisphosphate aldolase/phosphoglyeerate kinase.The proteosome was found in parasite exposed to 30μg/mL of the extract.Conclusions:Results suggest that proteins involved in the glycolysis pathway may be the targets for antimalarial activity of G.mangostana Linn.(pericarp).

  9. Antimalarials and the fight against malaria in Brazil.

    Science.gov (United States)

    Carmargo, Luiz Ma; de Oliveira, Saulo; Basano, Sergio; Garcia, Célia Rs

    2009-08-01

    Malaria, known as the "fevers," has been treated for over three thousand years in China with extracts of plants of the genus Artemisia (including Artemisia annua, A. opiacea, and A. lancea) from which the active compound is artemisin, a sesquiterpene that is highly effective in the treatment of the disease, especially against young forms of the parasite. South American Indians in the seventeenth century already used an extract of the bark of chinchona tree, commonly named "Jesuits' powder." Its active compound was isolated in 1820 and its use spread all over the world being used as a prophylactic drug during the construction of the Madeira-Mamoré railroad in the beginning of the twentieth century. During the 1920s to the 1940s, new antimalarial drugs were synthesized to increase the arsenal against this parasite. However, the parasite has presented systematic resistence to conventional antimalarial drugs, driving researchers to find new strategies to treat the disease. In the present review we discuss how Brazil treats Plasmodium-infected patients. PMID:19753125

  10. Proteomics analysis of antimalarial targets of Garcinia mangostana Linn.

    Institute of Scientific and Technical Information of China (English)

    Wanna Chaijaroenkul; Artitiya Thiengsusuk; Kanchana Rungsihirunrat; Stephen Andrew Ward; Kesara Na-Bangchang

    2014-01-01

    Objective: To investigate possible protein targets for antimalarial activity of Garcinia mangostana Linn. (G. mangostana) (pericarp) in 3D7 Plasmodium falciparum clone using 2-dimensional electrophoresis and liquid chromatography mass-spectrometry (LC/MS/MS). Methods: 3D7 Plasmodium falciparum was exposed to the crude ethanolic extract of G.mangostana Linn. (pericarp) at the concentrations of 12µg/mL (IC50 level: concentration that inhibits parasite growth by 50%) and 30 µg/mL (IC90 level: concentration that inhibits parasite growth by 90%) for 12 h. Parasite proteins were separated by 2-dimensional electrophoresis and identified by LC/MS/MS.Results:At the IC50 concentration, about 82% of the expressed parasite proteins were matched with the control (non-exposed), while at the IC90 concentration, only 15% matched proteins were found. The selected protein spots from parasite exposed to the plant extract at the concentration of 12 µg/mL were identified as enzymes that play role in glycolysis pathway, i.e., phosphoglycerate mutase putative, L-lactate dehydrogenase/glyceraldehyde-3-phosphate dehydrogenase, and fructose-bisphosphate aldolase/phosphoglycerate kinase. The proteosome was found in parasite exposed to 30 µg/mL of the extract.Conclusions:Results suggest that proteins involved in the glycolysis pathway may be the targets for antimalarial activity of G. mangostana Linn. (pericarp).

  11. In vitro evaluation of marketed antimalarial chloroquine phosphate tablets

    Directory of Open Access Journals (Sweden)

    Amit K. Patel, Bhupendra G. Prajapati, Rubina S. Moria & Chhaganbhai N. Patel

    2005-12-01

    Full Text Available Background & objectives: The aim of the present study is to investigate the physicochemicalequivalence of seven brands of tablets containing chloroquine phosphate, an antimalarial purchasedfrom different retail pharmacy outlets.Methods: The quality and physicochemical equivalence of seven different brands of chloroquinephosphate tablets were assessed. The assessment included the evaluation of uniformity of weight,friability, crushing strength, disintegration and dissolution tests as well as chemical assay of thetablets.Results: All the seven brands of the tablets passed the British Pharmacopoeia (BP standards foruniformity of weight, disintegration and crushing strength. One of seven brands failed the friabilitytest. One of the brands did not comply with the standard assay of content of active ingredients.Dissolution test passes the pharmacopoeial standards for chloroquine phosphate tablets. There wereno significant differences in the amounts of chloroquine phosphate released from the different brands.Interpretation & conclusion: Out of the seven brands of anti-malarial chloroquine phosphate tabletsonly one brand fails to meet BP quality specifications which shows constant market monitoring ofnew products to ascertain their equivalency to pharmacopoeial standards.

  12. Antimalarial drug resistance in Bangladesh, 1996-2012.

    Science.gov (United States)

    Haque, Ubydul; Glass, Gregory E; Haque, Waziul; Islam, Nazrul; Roy, Shyamal; Karim, Jahirul; Noedl, Harald

    2013-12-01

    Malaria remains an important health problem in Bangladesh, with approximately 14 million people at risk. Antimalarial drug resistance is a major obstacle to the control of malaria in endemic countries. In 2012, Bangladesh reported an estimated 29 522 malaria episodes, of which 94% were reported as being caused by Plasmodium falciparum. In this study, we reviewed and summarized antimalarial drug resistance data from Bangladesh published until June 2013. We searched published sources for data referring to any type of P. falciparum drug resistance (in vivo, in vitro, or molecular) and found 169 articles published in peer-reviewed journals. Of these, 143 articles were excluded because they did not meet our inclusion criteria. After detailed review of the remaining 26 articles, 14 were selected for evaluation. Published studies indicate that P. falciparum shows varying levels of resistance to chloroquine, mefloquine and sulfadoxine-pyrimethamine. Combination therapy of chloroquine and primaquine has proven ineffective and combinations of sulfadoxine-pyrimethamine with either quinine or chloroquine have also shown poor efficacy. Recent studies indicate that artemisinin derivatives, such as artesunate, remain highly efficacious in treating P. falciparum malaria. Available data suggest that artemisinins, quinine, doxycyline, mefloquine-artesunate and azithromycin-artesunate combination therapy remain efficacious in the treatment of P. falciparum malaria in Bangladesh.

  13. Maximizing antimalarial efficacy and the importance of dosing strategies.

    Science.gov (United States)

    Beeson, James G; Boeuf, Philippe; Fowkes, Freya J I

    2015-05-09

    Artemisinin-based combination therapies (ACTs) are the cornerstone for the treatment of malaria. However, confirmed resistance to artemisinins in South-East Asia, and reports of reduced efficacy of ACTs raise major concerns for malaria treatment and control. Without new drugs to replace artemisinins, it is essential to define dosing strategies that maximize therapeutic efficacy, limit the spread of resistance, and preserve the clinical value of ACTs. It is important to determine the extent to which reduced efficacy of ACTs reflects true resistance versus sub-optimal dosing, and quantify other factors that determine treatment failure. Pooled analyses of individual patient data from multiple clinical trials, by investigators in the Worldwide Antimalarial Resistance Network, have shown high overall efficacy for three widely used ACTs, artemether-lumefantrine, artesunate-amodiaquine, and dihydroartemisinin-piperaquine. Analyses also highlight that suboptimal dosing leads to increased risk of treatment failure, especially among children. In the most recent study, an analysis of clinical trials of artesunate-amodiaquine, widely used among children in Africa, revealed a superior efficacy for fixed-dose combination tablets compared to loose non-fixed dose combinations. This highlights the benefits of fixed-dose combinations as a practical strategy for ensuring optimal antimalarial dosing and maximizing efficacy. Please see related article: http://www.biomedcentral.com/1741-7015/13/66.

  14. Fake anti-malarials: start with the facts.

    Science.gov (United States)

    Kaur, Harparkash; Clarke, Siȃn; Lalani, Mirza; Phanouvong, Souly; Guérin, Philippe; McLoughlin, Andrew; Wilson, Benjamin K; Deats, Michael; Plançon, Aline; Hopkins, Heidi; Miranda, Debora; Schellenberg, David

    2016-01-01

    This meeting report presents the key findings and discussion points of a 1-day meeting entitled 'Fake anti-malarials: start with the facts' held on 28th May 2015, in Geneva, Switzerland, to disseminate the findings of the artemisinin combination therapy consortium's drug quality programme. The teams purchased over 10,000 samples, using representative sampling approaches, from six malaria endemic countries: Equatorial Guinea (Bioko Island), Cambodia, Ghana, Nigeria, Rwanda and Tanzania. Laboratory analyses of these samples showed that falsified anti-malarials (<8 %) were found in just two of the countries, whilst substandard artemisinin-based combinations were present in all six countries and, artemisinin-based monotherapy tablets are still available in some places despite the fact that the WHO has urged regulatory authorities in malaria-endemic countries to take measures to halt the production and marketing of these oral monotherapies since 2007. This report summarizes the presentations that reviewed the public health impact of falsified and substandard drugs, sampling strategies, techniques for drug quality analysis, approaches to strengthen health systems capacity for the surveillance of drug quality, and the ensuing discussion points from the dissemination meeting. PMID:26873700

  15. Quantifying the pharmacology of antimalarial drug combination therapy

    Science.gov (United States)

    Hastings, Ian M.; Hodel, Eva Maria; Kay, Katherine

    2016-01-01

    Most current antimalarial drugs are combinations of an artemisinin plus a ‘partner’ drug from another class, and are known as artemisinin-based combination therapies (ACTs). They are the frontline drugs in treating human malaria infections. They also have a public-health role as an essential component of recent, comprehensive scale-ups of malaria interventions and containment efforts conceived as part of longer term malaria elimination efforts. Recent reports that resistance has arisen to artemisinins has caused considerable concern. We investigate the likely impact of artemisinin resistance by quantifying the contribution artemisinins make to the overall therapeutic capacity of ACTs. We achieve this using a simple, easily understood, algebraic approach and by more sophisticated pharmacokinetic/pharmacodynamic analyses of drug action; the two approaches gave consistent results. Surprisingly, the artemisinin component typically makes a negligible contribution (≪0.0001%) to the therapeutic capacity of the most widely used ACTs and only starts to make a significant contribution to therapeutic outcome once resistance has started to evolve to the partner drugs. The main threat to antimalarial drug effectiveness and control comes from resistance evolving to the partner drugs. We therefore argue that public health policies be re-focussed to maximise the likely long-term effectiveness of the partner drugs. PMID:27604175

  16. Quantifying the pharmacology of antimalarial drug combination therapy

    Science.gov (United States)

    Hastings, Ian M.; Hodel, Eva Maria; Kay, Katherine

    2016-09-01

    Most current antimalarial drugs are combinations of an artemisinin plus a ‘partner’ drug from another class, and are known as artemisinin-based combination therapies (ACTs). They are the frontline drugs in treating human malaria infections. They also have a public-health role as an essential component of recent, comprehensive scale-ups of malaria interventions and containment efforts conceived as part of longer term malaria elimination efforts. Recent reports that resistance has arisen to artemisinins has caused considerable concern. We investigate the likely impact of artemisinin resistance by quantifying the contribution artemisinins make to the overall therapeutic capacity of ACTs. We achieve this using a simple, easily understood, algebraic approach and by more sophisticated pharmacokinetic/pharmacodynamic analyses of drug action; the two approaches gave consistent results. Surprisingly, the artemisinin component typically makes a negligible contribution (≪0.0001%) to the therapeutic capacity of the most widely used ACTs and only starts to make a significant contribution to therapeutic outcome once resistance has started to evolve to the partner drugs. The main threat to antimalarial drug effectiveness and control comes from resistance evolving to the partner drugs. We therefore argue that public health policies be re-focussed to maximise the likely long-term effectiveness of the partner drugs.

  17. Synthesis and structure of interaction products of quinoline-2(1H)-thione with molecular iodine.

    Science.gov (United States)

    Chernov'yants, Margarita S; Starikova, Zoya A; Kolesnikova, Tatiana S; Karginova, Anastasia O; Lyanguzov, Nikolay V

    2015-03-15

    The behavior of quinoline-2(1H)-thione, which is a potential antithyroid drug toward molecular iodine, was investigated. The ability of quinoline-2(1H)-thione to form the outer-sphere charge-transfer complex C9H7NS·I2 with iodine molecular in dilute chloroform solution has been studied by UV-vis spectroscopy (lgβ=3.85). The crystal structure of the new salt 2-(quinoline-2-yldisulfanyl)quinolinium triiodide - product of irreversible oxidation of quinoline-2(1H)-thione was determined by X-ray diffraction. The 2-(quinoline-2-yldisulfanyl)quinolinium cations form dimers through π-π-stacking interaction between quinoline rings. Strong intramolecular interactions are observed between iodine - sulfur atoms and iodine - hydrogen atoms with shortened contacts (less of sum of van der Waals contacts). It is noteworthy that two perfectly centrosymmetrical anions I3(-) form a very short contact I(3)⋯I(3') 3.7550(5) so we can state the formation of the dianion I(6)(2-). Therefore the formation and topology of polyiodide species depend on the characteristics, such as shape, size and charge, etc., of the counter cation, 2-(quinoline-2-yldisulfanyl)quinolinium, which is considered as templating agent.

  18. Phosphotungstic Acid: An Efficient, Cost-effective and Recyclable Catalyst for the Synthesis of Polysubstituted Quinolines

    Directory of Open Access Journals (Sweden)

    Sahareh Bashiribod

    2009-03-01

    Full Text Available Phosphotungstic acid (H3PW12O40 was used as an efficient and recyclable catalyst for the synthesis of polysubstituted quinolines through the Friedländer condensation of 2-aminoarylketone with carbonyl compounds, which was achieved by conventional heating under solvent-free conditions.

  19. Palladium-Catalyzed Intermolecular Aerobic Annulation of o-Alkenylanilines and Alkynes for Quinoline Synthesis.

    Science.gov (United States)

    Zheng, Jia; Li, Zun; Huang, Liangbin; Wu, Wanqing; Li, Jianxiao; Jiang, Huanfeng

    2016-08-01

    A new approach to construct 2,3-disubstituted quinolines is described via Pd-catalyzed oxidative cyclization of o-vinylanilines and alkynes with molecular oxygen. This transformation is supposed to undergo intermolecular amination of alkyne, insertion of the olefin, and oxidative cleavage of C-C bond sequence. PMID:27418021

  20. Synthesis, Characterization and Anti-Cancer Activity of Hydrazide Derivatives Incorporating a Quinoline Moiety.

    Science.gov (United States)

    Bingul, Murat; Tan, Owen; Gardner, Christopher R; Sutton, Selina K; Arndt, Greg M; Marshall, Glenn M; Cheung, Belamy B; Kumar, Naresh; Black, David StC

    2016-01-01

    Identification of the novel (E)-N'-((2-chloro-7-methoxyquinolin-3-yl)methylene)-3-(phenylthio)propanehydrazide scaffold 18 has led to the development of a new series of biologically active hydrazide compounds. The parent compound 18 and new quinoline derivatives 19-26 were prepared from the corresponding quinoline hydrazones and substituted carboxylic acids using EDC-mediated peptide coupling reactions. Further modification of the parent compound 18 was achieved by replacement of the quinoline moiety with other aromatic systems. All the newly synthesized compounds were evaluated for their anti-cancer activity against the SH-SY5Y and Kelly neuroblastoma cell lines, as well as the MDA-MB-231 and MCF-7 breast adenocarcinoma cell lines. Analogues 19 and 22 significantly reduced the cell viability of neuroblastoma cancer cells with micromolar potency and significant selectivity over normal cells. The quinoline hydrazide 22 also induced G₁ cell cycle arrest, as well as upregulation of the p27(kip1) cell cycle regulating protein. PMID:27428941

  1. Synthesis, Characterization and Anti-Cancer Activity of Hydrazide Derivatives Incorporating a Quinoline Moiety

    Directory of Open Access Journals (Sweden)

    Murat Bingul

    2016-07-01

    Full Text Available Identification of the novel (E-N′-((2-chloro-7-methoxyquinolin-3-ylmethylene-3-(phenylthiopropanehydrazide scaffold 18 has led to the development of a new series of biologically active hydrazide compounds. The parent compound 18 and new quinoline derivatives 19–26 were prepared from the corresponding quinoline hydrazones and substituted carboxylic acids using EDC-mediated peptide coupling reactions. Further modification of the parent compound 18 was achieved by replacement of the quinoline moiety with other aromatic systems. All the newly synthesized compounds were evaluated for their anti-cancer activity against the SH-SY5Y and Kelly neuroblastoma cell lines, as well as the MDA-MB-231 and MCF-7 breast adenocarcinoma cell lines. Analogues 19 and 22 significantly reduced the cell viability of neuroblastoma cancer cells with micromolar potency and significant selectivity over normal cells. The quinoline hydrazide 22 also induced G1 cell cycle arrest, as well as upregulation of the p27kip1 cell cycle regulating protein.

  2. Anxiogenic activity of quinolinic acid and kynurenine in the social interaction test in mice.

    Science.gov (United States)

    Lapin, I P; Mutovkina, L G; Ryzov, I V; Mirzaev, S

    1996-01-01

    Quinolinic acid, a metabolite of tryptophan on the kynurenine pathway, shortened the duration of social contacts (sniffings) in C57BL/6 mice which had been previously isolated for 24 h. This effect was observed at the following time intervals after i.c.v. administration: 2-6, 22-26 and 32-36 min. Locomotion was significantly less inhibited and only during the first interval. L-Kynurenine sulphate was less active. It shortened the duration of contacts only during the 32-36 min interval after i.c.v. administration. Grooming was significantly reduced by quinolinic acid at 7-11, 12-16 and 17-21 min after administration. These effects of quinolinic acid in the social interaction test are similar to those of standard anxiogens and suggest that quinolinic acid belongs to the putative endogenous anxiogens (and not only to the endogenous convulsants). The same assumption about L-kynurenine based on data in other models of anxiety has been made previously.

  3. Degradation of quinoline by wet oxidation - kinetic aspects and reaction mechanisms

    DEFF Research Database (Denmark)

    Thomsen, A.B.

    1998-01-01

    of succinic acid is suggested to be a result of a coupling reaction of the acetic acid radical A reaction mechanism is suggested for the degradation of quinoline: it involves hydroxyl radicals and the possible interaction with autoclave walls is discussed. (C) 1998 Elsevier Science Ltd. All rights reserved....

  4. Self-Assembly of a Library of Polyborate Chiral Anions for Asymmetric Catalytic Quinoline Reduction

    Science.gov (United States)

    Desai, Aman A.; Guan, Yong; Odom, Aaron L.; Majumder, Supriyo; Wulff, William D.

    2015-01-01

    The ‘template’ polyborate BOROX catalysts are shown to mediate the asymmetric transfer hydrogenation of 2-quinolines. The rapid and simple generation of a large family of BOROX catalysts with significantly altered asymmetric pockets is described. A transition state model that explains the enantioselectivity is proposed. PMID:26034335

  5. Synthesis and cytotoxic activity of 2,5-disubstituted pyrimido [5,4-c] quinoline derivatives

    Institute of Scientific and Technical Information of China (English)

    Fan Zhang; Xin Zhai; Li Juan Chen; Jian Guo Qi; Bo Cui; Yu Cheng Gu; Ping Gong

    2011-01-01

    A series of 2,5-disubstituted pyrimido[5,4-c]quinoline derivatives were synthesized and their cytotoxic activity against H460, HT-29 and MDA-MB-231 cell lines was evaluated in vitro. It was found that most of the tested compounds especially compound 17, shown stronger activity to the selected three cell lines than ZM447439.

  6. Unusual case of methanol poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Shapiro, L.; Henderson, M. (St. James' s Univ. Hospital, Leeds (United Kingdom). Dept. of Chemical Pathology); Madi, S.; Mellor, L. (St. James' s Univ. Hospital, Leeds (United Kingdom). Dept. of Medicine, and Pharmacy)

    1993-01-09

    A 31-year-old man with a history of alcohol abuse presented to the accident and emergency department complaining of blurred vision. 4 h previously he had drunk 300 mL de-icer fluid. Electrolytes, urea, creatinine, glucose, and blood-gas analysis were normal. Measured osmolality, however, was 368 mosmol/kg with a calculated osmolality of 300 mosmol/kg, which indicated a greatly increased osmolar gap. He was therefore given 150 mL whisky and admitted. Methanol was later reported as 200 mg/dL. Ethylene glycol was not detected, but another glycol, propylene glycol, was present at 47 mg/dL. 10 h after ingestion an intravenous infusion of ethanol was started and he was hemodialysed for 7 h. After dialysis he was given a further 100 mL whisky and the rate of ethanol infusion was reduced to 11 g per h. Methanol and ethanol were measured twice daily until methanol was under 10/mg/dL: The recommendation is that blood ethanol be maintained between 100 and 200 mg/dL during treatment of methanol poisoning. This concentration was not achieved, presumably because of the high rate of ethanol metabolism often found in alcoholics. Antifreeze solutions commonly contain methanol and ethylene glycol. Sometimes propylene glycol is substituted because it has properties similar to those of ethylene glycol but is less toxic. The authors postulate that propylene glycol inhibited the metabolism of methanol in the patient, thus sparing him from the toxic effects of methanol.

  7. 2-(2,4-Dichlorophenyl)-9-phenyl-2,3-dihydrothieno[3,2-b]quinoline

    OpenAIRE

    K. Balamurugan; D. Narmadha; Suresh, J.; Perumal, S.; P. L. Nilantha Lakshman

    2009-01-01

    In the title compound, C23H15Cl2NS, the quinoline system is almost planar [r.m.s. deviation = 0.013 (2) Å]. The phenyl group is disordered over two positions with site occupancies of 0.55 and 0.45, and is oriented in a nearly perpendicular configuration to the quinoline ring [the dihedral angles between the quinoline ring and the major and minor disordered components of the phenyl ring are 81.8 (2) and 71.6 (2)°, respectively]. The dih...

  8. ACUTE AND CHRONIC TOXICITY OF PHENYL QUINOLINE ON WATER FLEA DAPHNIA MAGNA

    Directory of Open Access Journals (Sweden)

    Hildebrando Ayala

    2012-06-01

    Full Text Available The aquatic ecotoxicological determination of phytonematicide products using the zooplanktonic cladoceran Daphnia magna is important for environmental risk assessment. Evaluations were made of the acute median lethal concentration (LC50 of phenyl quinoline on D. magna, that was 4.12 ug i.a. L-1 at 48 h of exposure. The chronic effects of phenyl quinoline in the mortality rate of the cladoceran D. magna at 17 d of exposure, with 0.18 ug ai L-1 of LOEC (Lowest Observed Effect Concentration and 0.072 ug ai L-1 of NOEC (No Observed Effect Concentration were determined. Evaluations of the chronic effect of phenyl quinoline on three parameters of growth of D. magna (total length, antenna length and caudal length to 17 d of exposure, only showed significant differences in length of the antenna between the control and 0.072 ug ai L-1 been this the value of LOEC and thus the lower concentration 0.0288 ug ai L-1, the NOEC value for phenyl quinoline. The ratio between acute and chronic toxicity (RAC for the relationship showed acute 48 h exposure on mortality NOEC 17 d a value of 57.22, and for the ratio of acute NOEC on of the length of the antenna to 17 d was a value of 143. The environmental risk assessment (ERA shows that the PEC (Probable Effect Concentration / PNEC (Predicted No-Effect Concentration for acute assay was 582 524 and for the PEC / PNEC for chronic test was 83 333 333. These results demonstrate that phenyl quinoline has a high impact on aquatic biota represented by the trophic level that belongs to D. magna, and therefore shows that the substance is a candidate for a comprehensive ecotoxicological assessment.

  9. The washout effect during laundry on benzothiazole, benzotriazole, quinoline, and their derivatives in clothing textiles.

    Science.gov (United States)

    Luongo, Giovanna; Avagyan, Rozanna; Hongyu, Ren; Östman, Conny

    2016-02-01

    In two previous papers, the authors have shown that benzothiazole, benzotriazole, quinoline, and several of their derivatives are widespread in clothing textile articles. A number of these compounds exhibit allergenic and irritating properties and, due to their octanol-water partition coefficient, are prone to be absorbed by the skin. Moreover, they are slightly soluble in water, which could make washing of clothes a route of emission into the environment. In the present study, the washout effect of benzothiazole, benzotriazole, quinoline, and some of their derivatives has been investigated. Twenty-seven textile samples were analyzed before, as well as after five and ten times of washing. The most abundant analyte was found to be benzothiazole, which was detected in 85 % of the samples with an average concentration of 0.53 μg/g (median 0.44 μg/g), followed by quinoline, detected in 81 % of the samples with an average concentration of 2.42 μg/g (median 0.21 μg/g). The average decrease in concentration for benzothiazoles was 50 % after ten times washing, while it was around 20 % for quinolines. The average emission to household wastewater of benzothiazoles and quinolines during one washing (5 kg of clothes made from polyester materials) was calculated to 0.5 and 0.24 g, respectively. These results strongly indicate that laundering of clothing textiles can be an important source of release of these compounds to household wastewater and in the end to aquatic environments. It also demonstrates a potential source of human exposure to these chemicals since considerable amounts of the compounds remain in the clothes even after ten times of washing.

  10. Antimalarial Activity of KAF156 in Falciparum and Vivax Malaria.

    Science.gov (United States)

    White, Nicholas J; Duong, Tran T; Uthaisin, Chirapong; Nosten, François; Phyo, Aung P; Hanboonkunupakarn, Borimas; Pukrittayakamee, Sasithon; Jittamala, Podjanee; Chuthasmit, Kittiphum; Cheung, Ming S; Feng, Yiyan; Li, Ruobing; Magnusson, Baldur; Sultan, Marc; Wieser, Daniela; Xun, Xiaolei; Zhao, Rong; Diagana, Thierry T; Pertel, Peter; Leong, F Joel

    2016-09-22

    Background KAF156 belongs to a new class of antimalarial agents (imidazolopiperazines), with activity against asexual and sexual blood stages and the preerythrocytic liver stages of malarial parasites. Methods We conducted a phase 2, open-label, two-part study at five centers in Thailand and Vietnam to assess the antimalarial efficacy, safety, and pharmacokinetic profile of KAF156 in adults with acute Plasmodium vivax or P. falciparum malaria. Assessment of parasite clearance rates in cohorts of patients with vivax or falciparum malaria who were treated with multiple doses (400 mg once daily for 3 days) was followed by assessment of the cure rate at 28 days in a separate cohort of patients with falciparum malaria who received a single dose (800 mg). Results Median parasite clearance times were 45 hours (interquartile range, 42 to 48) in 10 patients with falciparum malaria and 24 hours (interquartile range, 20 to 30) in 10 patients with vivax malaria after treatment with the multiple-dose regimen and 49 hours (interquartile range, 42 to 54) in 21 patients with falciparum malaria after treatment with the single dose. Among the 21 patients who received the single dose and were followed for 28 days, 1 had reinfection and 7 had recrudescent infections (cure rate, 67%; 95% credible interval, 46 to 84). The mean (±SD) KAF156 terminal elimination half-life was 44.1±8.9 hours. There were no serious adverse events in this small study. The most common adverse events included sinus bradycardia, thrombocytopenia, hypokalemia, anemia, and hyperbilirubinemia. Vomiting of grade 2 or higher occurred in 2 patients, 1 of whom discontinued treatment because of repeated vomiting after receiving the single 800-mg dose. More adverse events were reported in the single-dose cohort, which had longer follow-up, than in the multiple-dose cohorts. Conclusions KAF156 showed antimalarial activity without evident safety concerns in a small number of adults with uncomplicated P. vivax or P

  11. Antimalarial activity of selected Sudanese medicinal plants with emphasis to Maytenus senegalensis

    International Nuclear Information System (INIS)

    The aim of the present study is to identify and characterize the antimalrial agents from traitional Sudanese medicinal plants. 49 plants parts representing 26 species from 15 families were extracted and screened for their in vitro antimalrial activity using P. falciparum strain 3D7 which is chloroquine sensitive and Dd2 strain which is chloroquine resistant and pyrimethamine sensitive.The plant species investigated exhibited diverse botanical families. They includes Annonaceae, Aristolochiaceae, Asteraceae, Balantiaceae, Caesalpiniceae, Celasteraceae, Cucurbitaceae, Fabaceae, Graminae, Meliaceae, Myrtaceae, Polygonaceae, Rubiaceae, Rutaceae, and simaroubaceae. The evaluation of these plants for their antimalarial activity and their effect on lymphocyte proliferation was carried out. 57 extracts were tested on the chloroquine sensitive strain (3D7). Where 34 extracts (59%) exhibited significant activity against 3D7 with IC50 values ≤ 50 μ g/ml. While 21 extracts (57%) showed antimalrial activities with IC50 values ≤ 50 μ g/ml on Dd2. 13 extracts (22%) and ten extracts (18%) only showed an activity with IC50 values ≤ 5 μ g/ml on 3 D7 and Dd2, respectively. The activities of some plant extracts, which affected 3D7 strain, were measured using the radiolabelled (3H) hypoxanthine method and microscopical count. 15 plant extracts (48%) from 32 showed IC50 values ≤ 50 μ g/ml against 3D7 strain using the radiolabelled hypoxanthine methods and only 5 extracts (16%) showed IC50 values ≤ 5 μ g/ml against 3D7. Most of the extracts screened had a low effect on lymphocyte proliferation (IC50 values >100 μ g/ml), where as Sonochous cornatus, Balanites aegyptiaca, Tamarindus indica, Acacia nilotica, Annona squamosa, Eucalyptus globulus and Cassia tora enhanced lymphocyte proliferation. liquid-liquid partition of methanolic preparation of Acacia nilotica seeds and husk showed that the ethylacetate phase possessed the highest activity against both 3D7 and Dd2 strains

  12. Trisubstituted Pyrimidines as Efficacious and Fast-Acting Antimalarials.

    Science.gov (United States)

    Norcross, Neil R; Baragaña, Beatriz; Wilson, Caroline; Hallyburton, Irene; Osuna-Cabello, Maria; Norval, Suzanne; Riley, Jennifer; Stojanovski, Laste; Simeons, Frederick R C; Porzelle, Achim; Grimaldi, Raffaella; Wittlin, Sergio; Duffy, Sandra; Avery, Vicky M; Meister, Stephan; Sanz, Laura; Jiménez-Díaz, Belén; Angulo-Barturen, Iñigo; Ferrer, Santiago; Martínez, María Santos; Gamo, Francisco Javier; Frearson, Julie A; Gray, David W; Fairlamb, Alan H; Winzeler, Elizabeth A; Waterson, David; Campbell, Simon F; Willis, Paul; Read, Kevin D; Gilbert, Ian H

    2016-07-14

    In this paper we describe the optimization of a phenotypic hit against Plasmodium falciparum, based on a trisubstituted pyrimidine scaffold. This led to compounds with good pharmacokinetics and oral activity in a P. berghei mouse model of malaria. The most promising compound (13) showed a reduction in parasitemia of 96% when dosed at 30 mg/kg orally once a day for 4 days in the P. berghei mouse model of malaria. It also demonstrated a rapid rate of clearance of the erythrocytic stage of P. falciparum in the SCID mouse model with an ED90 of 11.7 mg/kg when dosed orally. Unfortunately, the compound is a potent inhibitor of cytochrome P450 enzymes, probably due to a 4-pyridyl substituent. Nevertheless, this is a lead molecule with a potentially useful antimalarial profile, which could either be further optimized or be used for target hunting. PMID:27314305

  13. The antimalarial drug quinine interferes with serotonin biosynthesis and action.

    Science.gov (United States)

    Islahudin, Farida; Tindall, Sarah M; Mellor, Ian R; Swift, Karen; Christensen, Hans E M; Fone, Kevin C F; Pleass, Richard J; Ting, Kang-Nee; Avery, Simon V

    2014-01-01

    The major antimalarial drug quinine perturbs uptake of the essential amino acid tryptophan, and patients with low plasma tryptophan are predisposed to adverse quinine reactions; symptoms of which are similar to indications of tryptophan depletion. As tryptophan is a precursor of the neurotransmitter serotonin (5-HT), here we test the hypothesis that quinine disrupts serotonin function. Quinine inhibited serotonin-induced proliferation of yeast as well as human (SHSY5Y) cells. One possible cause of this effect is through inhibition of 5-HT receptor activation by quinine, as we observed here. Furthermore, cells exhibited marked decreases in serotonin production during incubation with quinine. By assaying activity and kinetics of the rate-limiting enzyme for serotonin biosynthesis, tryptophan hydroxylase (TPH2), we showed that quinine competitively inhibits TPH2 in the presence of the substrate tryptophan. The study shows that quinine disrupts both serotonin biosynthesis and function, giving important new insight to the action of quinine on mammalian cells.

  14. Drug resistance genomics of the antimalarial drug artemisinin.

    Science.gov (United States)

    Winzeler, Elizabeth A; Manary, Micah J

    2014-01-01

    Across the globe, over 200 million annual malaria infections result in up to 660,000 deaths, 77% of which occur in children under the age of five years. Although prevention is important, malaria deaths are typically prevented by using antimalarial drugs that eliminate symptoms and clear parasites from the blood. Artemisinins are one of the few remaining compound classes that can be used to cure multidrug-resistant Plasmodium falciparum infections. Unfortunately, clinical trials from Southeast Asia are showing that artemisinin-based treatments are beginning to lose their effectiveness, adding renewed urgency to the search for the genetic determinants of parasite resistance to this important drug class. We review the genetic and genomic approaches that have led to an improved understanding of artemisinin resistance, including the identification of resistance-conferring mutations in the P. falciparum kelch13 gene. PMID:25470531

  15. Screening Mangrove Endophytic Fungi for Antimalarial Natural Products

    Directory of Open Access Journals (Sweden)

    Laurent Calcul

    2013-12-01

    Full Text Available We conducted a screening campaign to investigate fungi as a source for new antimalarial compounds. A subset of our fungal collection comprising Chinese mangrove endophytes provided over 5000 lipophilic extracts. We developed an accelerated discovery program based on small-scale cultivation for crude extract screening and a high-throughput malaria assay. Criteria for hits were developed and high priority hits were subjected to scale-up cultivation. Extracts from large scale cultivation were fractionated and these fractions subjected to both in vitro malaria and cytotoxicity screening. Criteria for advancing fractions to purification were developed, including the introduction of a selectivity index and by dereplication of known metabolites. From the Chinese mangrove endophytes, four new compounds (14–16, 18 were isolated including a new dimeric tetrahydroxanthone, dicerandrol D (14, which was found to display the most favorable bioactivity profile.

  16. Immunochemical Analysis of the Antimalarial Drugs Artemisinin and Artesunate

    Directory of Open Access Journals (Sweden)

    Hiroyuki Tanaka

    2012-11-01

    Full Text Available We prepared a monoclonal antibody (mAb 1C1 showing specificity for artemisinin (AM and artesunate (AS, and we developed an indirect competitive enzyme-linked immunosorbent assay (icELISA using this novel mAb. Moreover, we prepared a recombinant antibody derived from mAb 1C1 in order to overcome insufficient mAb production by hybridoma culture. A recombinant antigen-binding fragment (Fab was easily constructed using antibody manipulation technologies and was produced by microorganisms in high yield. We herein review immunochemical approaches for analysis of the antimalarial drugs AM and AS that were able to yield analysis results for multiple samples in a short period of time using simple and reliable protocols.

  17. Triterpenes from Minquartia guianensis (Olacaceae) and in vitro antimalarial activity

    Energy Technology Data Exchange (ETDEWEB)

    Cursino, Lorena Mayara de Carvalho; Nunez, Cecilia Veronica [Instituto Nacional de Pesquisas da Amazonia (INPA), Manaus, AM (Brazil). Lab. de Bioprospeccao e Biotecnologia; Paula, Renata Cristina de; Nascimento, Maria Fernanda Alves do [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Fac. de Farmacia. Dept. de Produtos Farmaceuticos; Santos, Pierre Alexandre dos, E-mail: cecilia@inpa.gov.br [Universidade Federal do Amazonas (UFAM), Manaus, AM (Brazil). Fac. de Ciencias Farmaceuticas

    2012-07-01

    Minquartia guianensis, popularly known as acariquara, was phytochemically investigated. The following triterpenes were isolated from the dichloromethane extract of leaves: lupen-3-one (1), taraxer-3-one (2) and oleanolic acid (3). The dichloromethane extract of branches yielded the triterpene 3{beta}-methoxy-lup-20(29)-ene (4). The chemical structures were characterized by NMR data. Plant extracts, substance 3, squalene (5) and taraxerol (6), (5 and 6 previously isolated), were evaluated by in vitro assay against chloroquine resistant Plasmodium falciparum. The dichloromethane extract of leaves and the three triterpenes assayed have shown partial activity. Thus, these results demonstrated that new potential antimalarial natural products can be found even in partially active extracts. (author)

  18. Genetic relationship of organic bases of the quinoline and isoquinoline series from lignite semicoking tars with the initial biological material

    Energy Technology Data Exchange (ETDEWEB)

    Platonov, V.V.; Proskuryakov, V.A.; Podshibyakin, S.I.; Domogatskii, V.V.; Shvykin, A.Y.; Shavyrina, O.A.; Chilachava, K.B. [Leo Tolstoy State Pedagog University, Tula (Russian Federation)

    2002-07-01

    The genetic relationship of quinoline and isoquinoline compounds present in semicoking tars of Kimovsk lignites (near-Moscow fields) with the initial vegetable material is discussed. Transformation pathways of the native compounds in the course of lignite formation are suggested.

  19. 2-(2,4-Dichlorophenyl-9-phenyl-2,3-dihydrothieno[3,2-b]quinoline

    Directory of Open Access Journals (Sweden)

    K. Balamurugan

    2009-08-01

    Full Text Available In the title compound, C23H15Cl2NS, the quinoline system is almost planar [r.m.s. deviation = 0.013 (2 Å]. The phenyl group is disordered over two positions with site occupancies of 0.55 and 0.45, and is oriented in a nearly perpendicular configuration to the quinoline ring [the dihedral angles between the quinoline ring and the major and minor disordered components of the phenyl ring are 81.8 (2 and 71.6 (2°, respectively]. The dihydrothiene ring adopts an envelope conformation. The dihedral angle between the chlorophenyl ring and the quinoline system is 79.32 (1°. In the crystal weak C—H...π interactions occur.

  20. Formulation of nanotized curcumin and demonstration of its antimalarial efficacy

    Directory of Open Access Journals (Sweden)

    Ghosh A

    2014-11-01

    Full Text Available Aparajita Ghosh,1 Tanushree Banerjee,2 Suman Bhandary,1 Avadhesha Surolia31Division of Molecular Medicine, Bose Institute, Centenary Campus, Kolkata, West Bengal, India; 2Department of Biotechnology, University of Pune, Pune, India; 3Molecular Biophysics Unit, Indian Institute of Science, Bangalore, IndiaAim: The present study was conducted to overcome the disadvantages associated with the poor water solubility and low bioavailability of curcumin by synthesizing nanotized curcumin and demonstrating its efficacy in treating malaria. Materials and methods: Nanotized curcumin was prepared by a modified emulsion-diffusion-evaporation method and was characterized by means of transmission electron microscopy, atomic force microscopy, dynamic light scattering, Zetasizer, Fourier transform infrared spectroscopy, and differential thermal analysis. The novelty of the prepared nanoformulation lies in the fact that it was devoid of any polymeric matrices used in conventional carriers. The antimalarial efficacy of the prepared nanotized curcumin was then checked both in vitro and in vivo. Results: The nanopreparation was found to be non-toxic and had a particle size distribution of 20–50 nm along with improved aqueous dispersibility and an entrapment efficiency of 45%. Nanotized curcumin (half maximal inhibitory concentration [IC50]: 0.5 µM was also found to be ten-fold more effective for growth inhibition of Plasmodium falciparum in vitro as compared to its native counterpart (IC50: 5 µM. Oral bioavailability of nanotized curcumin was found to be superior to that of its native counterpart. Moreover, when Plasmodium berghei-infected mice were orally treated with nanotized curcumin, it prolonged their survival by more than 2 months with complete clearance of parasites in comparison to the untreated animals, which survived for 8 days only. Conclusion: Nanotized curcumin holds a considerable promise in therapeutics as demonstrated here for treating malaria

  1. Epidemiological models for the spread of anti-malarial resistance

    Directory of Open Access Journals (Sweden)

    Antia R

    2003-02-01

    Full Text Available Abstract Background The spread of drug resistance is making malaria control increasingly difficult. Mathematical models for the transmission dynamics of drug sensitive and resistant strains can be a useful tool to help to understand the factors that influence the spread of drug resistance, and they can therefore help in the design of rational strategies for the control of drug resistance. Methods We present an epidemiological framework to investigate the spread of anti-malarial resistance. Several mathematical models, based on the familiar Macdonald-Ross model of malaria transmission, enable us to examine the processes and parameters that are critical in determining the spread of resistance. Results In our simplest model, resistance does not spread if the fraction of infected individuals treated is less than a threshold value; if drug treatment exceeds this threshold, resistance will eventually become fixed in the population. The threshold value is determined only by the rates of infection and the infectious periods of resistant and sensitive parasites in untreated and treated hosts, whereas the intensity of transmission has no influence on the threshold value. In more complex models, where hosts can be infected by multiple parasite strains or where treatment varies spatially, resistance is generally not fixed, but rather some level of sensitivity is often maintained in the population. Conclusions The models developed in this paper are a first step in understanding the epidemiology of anti-malarial resistance and evaluating strategies to reduce the spread of resistance. However, specific recommendations for the management of resistance need to wait until we have more data on the critical parameters underlying the spread of resistance: drug use, spatial variability of treatment and parasite migration among areas, and perhaps most importantly, cost of resistance.

  2. Distillation Time as Tool for Improved Antimalarial Activity and Differential Oil Composition of Cumin Seed Oil

    Science.gov (United States)

    A steam distillation extraction kinetics experiment was conducted to estimate essential oil yield, composition, antimalarial, and antioxidant capacity of cumin (Cuminum cyminum L.) seed (fruits). Furthermore, regression models were developed to predict essential oil yield and composition for a given...

  3. Crystal Structure of Norfloxacin Methanol Solvate: C16H18FN3O3·CH3OH·H2O

    Institute of Scientific and Technical Information of China (English)

    WANG Ying; SUN Li-Wei; WANG Wei; YAN Lian-He

    2005-01-01

    Norfloxacin methanol solvate (1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid methanol solvate) has been prepared. The crystal and molecular struc- tures of the title compound, C16H18FN3O3·CH3OH·H2O, were determined by X-ray diffraction me- thod. The compound crystallizes in monoclinic, space group P21/c with a = 7.8660(16), b = 22.525 (5), c = 10.253(2)(A), β = 108.31°, Mr = 369.39, V = 1724.7(6) (A)3, Z = 4, Dc = 1.423 g/cm3, F(000) = 784, R = 0.0557 and wR = 0.1224. The TGA analysis indicates that it decomposes completely at 723.75 ℃.

  4. Self-Medication with Antibiotics and Antimalarials in the Community of Silte Zone, South Ethiopia

    OpenAIRE

    Nasir Tajure Wabe; Dargicho Ahmed; Mulugeta Tarekegn Angamo

    2012-01-01

    AIM: Self-medication with antibiotics and antimalarials occurs among the population in Ethiopian. We studied to estimate the prevalence of self-medication with antibiotics and antimalarials in Ethiopia and evaluate factors associated with self-medications. METHODS: A cross-sectional study was conducted on 405 households, selected from Silte Zone in South Ethiopia, using a random sampling technique by employing a pretested questionnaire. Data were analyzed using SPSS for windows version 16.0. ...

  5. In vitro antimalarial activity of different extracts of Eremostachys macrophylla Montbr. & Auch.

    OpenAIRE

    Solmaz Asnaashari; Fariba Heshmati Afshar; Atefeh Ebrahimi; Sedigheh Bamdad Moghaddam; Abbas Delazar

    2015-01-01

    Introduction: The risk of drug resistance and the use of medicinal plants in malaria prevention and treatment have led to the search for new antimalarial compounds with natural origin. Methods: In the current study, six extracts with different polarity from aerial parts and rhizomes of Eremostachys macrophylla Montbr. & Auch., were screened for their antimalarial properties by cell-free beta-hematin formation assay. Results: Dichloromethane (DCM) extracts of both parts of plant showed s...

  6. Antimalarial qinghaosu/artemisinin: The therapy worthy of a Nobel Prize

    OpenAIRE

    Jerapan Krungkrai; Sudaratana Rochanakij Krungkrai

    2016-01-01

    Malaria is a major cause of human morbidity and mortality in the tropical endemic countries worldwide. This is largely due to the emergence and spread of resistance to most antimalarial drugs currently available. Based on the World Health Organization recommendation, artemisinin-based combination therapies are now used as first-line treatment for Plasmodium falciparum malaria. Artemisinin or qinghaosu (Chinese name) and its derivatives are highly potent, rapidly acting antimalarial drugs. Art...

  7. Poor quality vital anti-malarials in Africa - an urgent neglected public health priority.

    OpenAIRE

    Newton Paul N; Green Michael D; Mildenhall Dallas C; Plançon Aline; Nettey Henry; Nyadong Leonard; Hostetler Dana M; Swamidoss Isabel; Harris Glenn A; Powell Kristen; Timmermans Ans E; Amin Abdinasir A; Opuni Stephen K; Barbereau Serge; Faurant Claude

    2011-01-01

    Abstract Background Plasmodium falciparum malaria remains a major public health problem. A vital component of malaria control rests on the availability of good quality artemisinin-derivative based combination therapy (ACT) at the correct dose. However, there are increasing reports of poor quality anti-malarials in Africa. Methods Seven collections of artemisinin derivative monotherapies, ACT and halofantrine anti-malarials of suspicious quality were collected in 2002/10 in eleven African coun...

  8. Post-marketing surveillance of anti-malarial medicines used in Malawi

    OpenAIRE

    Chikowe, Ibrahim; Osei-Safo, Dorcas; Harrison, Jerry JEK; Konadu, Daniel Y; Addae-Mensah, Ivan

    2015-01-01

    Background The growing concern over the extent of anti-malarial medicine resistance in sub-Saharan Africa, driven largely by administration of sub-therapeutic doses derived from falsified and substandard medicines necessitates regular monitoring of the quality of these medicines to avert any potential public health disaster. This study aimed at determining the active pharmaceutical ingredient (API) content of anti-malarial medicines available in Malawi with respect to the manufacturers’ label...

  9. Synthesis and cytotoxic activity of 2-methylimidazo[1,2-a]pyridine- and quinoline-substituted 2-aminopyrimidine derivatives.

    Science.gov (United States)

    Vilchis-Reyes, Miguel Angel; Zentella, Alejandro; Martínez-Urbina, Miguel Angel; Guzmán, Angel; Vargas, Omar; Ramírez Apan, María Teresa; Ventura Gallegos, José Luis; Díaz, Eduardo

    2010-01-01

    A series of 2-methylimidazo[1,2-a]pyridine- and quinoline-substituted 2-aminopyrimidines derivatives were synthesized using a convenient synthetic route. We evaluate the isosteric replacement of methyl groups in 4-(2-methylimidazo[1,2-a]pyridin-3-yl)-N-p-tolylpyrimidin-2-amine (compound 1) by trifluoromethyl groups and the isosteric substitution of the 2-methylimidazo[1,2-a]pyridin-3-yl scaffold by quinolin-4-yl or quinolin-3-yl moieties. The replacement of hydrogen by fluorine does not affect notably the cytotoxic activity and CDK inhibitor activity in this series. Quinolin-4-yl-substituted compound, 8, presents cytotoxic activity and is most effective and selective against CDK1/CycA than against CDK2/CycB. Compound 11, which has a quinolin-3-yl moiety is CDK inhibitor but presents null cytotoxic activity. Quinolin-4-yl-substituted compounds constitute a new lead of cytotoxic and CDK inhibitor compounds from which more compelling and selective inhibitors can be designed. PMID:19879023

  10. Rational Design of Antimalarial Drugs Using Molecular Modeling and Statistical Analysis.

    Science.gov (United States)

    Santos, Cleydson Breno Rodrigues dos; Lobato, Cleison Carvalho; Braga, Francinaldo Sarges; Costa, Josivan da Silva; Favacho, Hugo Alexandre Silva; Carvalho, Jose Carlos Tavares; Macedo, Williams Jorge da Cruz; Brasil, Davi Do Socorro Barros; Silva, Carlos Henrique Tomich de Paula da; Silva Hage-Melim, Lorane Izabel da

    2015-01-01

    Artemisinin is an antimalarial compound isolated from Artemisia annua L. that is effective against Plasmodium falciparum. This paper proposes the development of new antimalarial derivatives of artemisinin from a SAR study and statistical analysis by multiple linear regression (MLR). The HF/6-31G** method was used to determine the molecular properties of artemisinin and 10 derivatives with antimalarial action. MEP maps and molecular docking were used to study the interface between ligand and receptor (heme). The Pearson correlation was used to choose the most important properties interrelated to the antimalarial activity: Hydration Energy (HE), Energy of the Complex (Ecplex), bond length (FeO1), and maximum index of R/Electronegativity of Sanderson (RTe+). After the Pearson correlation, 72 MLR models were built between antimalarial activity and molecular properties; the statistical quality of the models was evaluated by means of correlation coefficient (r), squared correlation coefficient (r(2)), explained variance (adjusted R(2)), standard error of estimate (SEE), and variance ratio (F), and only four models showed predictive ability. The selected models were used to predict the antimalarial activity of ten new artemisinin derivatives (test set) with unknown activity, and only eight of these compounds were predicted to be more potent than artemisinin, and were therefore subjected to theoretical studies of pharmacokinetic and toxicological properties. The test set showed satisfactory results for six new artemisinin compounds which is a promising factor for future synthesis and biological assays. PMID:26017698

  11. Study of the antimalarial properties of hydroxyethylamine derivatives using green fluorescent protein transformed Plasmodium berghei

    Directory of Open Access Journals (Sweden)

    Mariana Conceição Souza

    2015-06-01

    Full Text Available A rapid decrease in parasitaemia remains the major goal for new antimalarial drugs and thus, in vivo models must provide precise results concerning parasitaemia modulation. Hydroxyethylamine comprise an important group of alkanolamine compounds that exhibit pharmacological properties as proteases inhibitors that has already been proposed as a new class of antimalarial drugs. Herein, it was tested the antimalarial property of new nine different hydroxyethylamine derivatives using the green fluorescent protein (GFP-expressing Plasmodium berghei strain. By comparing flow cytometry and microscopic analysis to evaluate parasitaemia recrudescence, it was observed that flow cytometry was a more sensitive methodology. The nine hydroxyethylamine derivatives were obtained by inserting one of the following radical in the para position: H, 4Cl, 4-Br, 4-F, 4-CH3, 4-OCH3, 4-NO2, 4-NH2 and 3-Br. The antimalarial test showed that the compound that received the methyl group (4-CH3 inhibited 70% of parasite growth. Our results suggest that GFP-transfected P. berghei is a useful tool to study the recrudescence of novel antimalarial drugs through parasitaemia examination by flow cytometry. Furthermore, it was demonstrated that the insertion of a methyl group at the para position of the sulfonamide ring appears to be critical for the antimalarial activity of this class of compounds.

  12. Towards a methanol economy based on homogeneous catalysis: methanol to H2 and CO2 to methanol

    DEFF Research Database (Denmark)

    Alberico, E.; Nielsen, Martin

    2015-01-01

    The possibility to implement both the exhaustive dehydrogenation of aqueous methanol to hydrogen and CO2 and the reverse reaction, the hydrogenation of CO2 to methanol and water, may pave the way to a methanol based economy as part of a promising renewable energy system. Recently, homogeneous...

  13. Does anti-malarial drug knowledge predict anti-malarial dispensing practice in drug outlets? A survey of medicine retailers in western Kenya

    Directory of Open Access Journals (Sweden)

    Rusk Andria

    2012-08-01

    Full Text Available Abstract Background Malaria is a major cause of morbidity and mortality in Kenya, where it is the fifth leading cause of death in both children and adults. Effectively managing malaria is dependent upon appropriate treatment. In Kenya, between 17 to 83 percent of febrile individuals first seek treatment for febrile illness over the counter from medicine retailers. Understanding medicine retailer knowledge and behaviour in treating suspected malaria and dispensing anti-malarials is crucial. Methods To investigate medicine retailer knowledge about anti-malarials and their dispensing practices, a survey was conducted of all retail drug outlets that sell anti-malarial medications and serve residents of the Webuye Health and Demographic Surveillance Site in the Bungoma East District of western Kenya. Results Most of the medicine retailers surveyed (65% were able to identify artemether-lumefantrine (AL as the Kenyan Ministry of Health recommended first-line anti-malarial therapy for uncomplicated malaria. Retailers who correctly identified this treatment were also more likely to recommend AL to adult and paediatric customers. However, the proportion of medicine retailers who recommend the correct treatment is disappointingly low. Only 48% would recommend AL to adults, and 37% would recommend it to children. It was discovered that customer demand has an influence on retailer behaviour. Retailer training and education were found to be correlated with anti-malarial drug knowledge, which in turn is correlated with dispensing practices. Medicine retailer behaviour, including patient referral practice and dispensing practices, are also correlated with knowledge of the first-line anti-malarial medication. The Kenya Ministry of Health guidelines were found to influence retailer drug stocking and dispensing behaviours. Conclusion Most medicine retailers could identify the recommended first-line treatment for uncomplicated malaria, but the percentage that could

  14. PEG-SO3H as a catalyst in aqueous media: A simple, proficient and green approach for the synthesis of quinoline derivatives

    Indian Academy of Sciences (India)

    M A Nasseri; S A Alavi; B Zakerinasab

    2013-01-01

    A convenient and efficient method was developed for the synthesis of quinolines, an important class of potentially bioactive compounds. The quinoline derivatives were prepared in water, an excellent solvent in terms of environmental impact and with reduced waste production. PEG-SO3H effectively catalysed the one-pot synthesis of quinolines by the condensation of -aminoaryl ketones and carbonyl compound with high yields (75-95%). The compounds were isolated by simple filtration in a high purity form.

  15. An unusual presentation of methanol poisoning

    OpenAIRE

    TURMEN, Suha; ERYİĞİT, Umut; SAHİN, Aynur; MENTESE, Seda; Gunduz, Abdulkadir

    2014-01-01

    Methanol is a substance possessing high toxicity even in small quantities. It may lead to intracerebral hemorrhage, blindness and death. Methanol poisoning generally takes place as result of oral ingestion, but may rarely occur through inhalation or transdermally. Persons may be exposed to methanol because of illegal alcohol beverage producers or alternative medicine providers. A 55-year-old male with methanol poisoning as a result of rubbing a self-prepared mixture of methylated spirit and a...

  16. Synthesis, crystal structure, optical and electrochemical properties of 9,10-dihydroxybenzo[ℎ]quinoline

    Indian Academy of Sciences (India)

    Kew-Yu Chen; Hsing-Yang Tsai; Wei-Chi Lin; Hou-Hsein Chu; Yu-Ching Weng; Chih-Chieh Chan

    2014-07-01

    9,10-Dihydroxybenzo[ℎ]quinoline (1), a 10-hydroxybenzo[ℎ]quinoline (2) derivative, was synthesized and characterized by 1H NMR, 13C NMR, UV-vis and fluorescence spectra, and single-crystal X-ray diffraction. Compound 1 possesses an intramolecular six-membered-ring hydrogen bond, from which excitedstate intramolecular proton transfer (ESIPT) takes place from the phenolic proton to the pyridinic nitrogen, resulting in a proton-transfer tautomer emission of 650 nm in dichloromethane. Its molecular geometry in the ground state has also been calculated using density functional theory (DFT) at the B3LYP/6-31G∗∗ level and compared with its crystal structure. Results show that the optimized geometry can well reproduce the crystal structure. Furthermore, both absorption and emission spectra of 1 and 2 were calculated using time-dependent DFT (TD-DFT) calculations, and were in good agreement with the experimental results.

  17. Optimization of the Separation of Quinolines in Micellar Liquid Chromatography by Experimental Design and Regression Models

    Institute of Scientific and Technical Information of China (English)

    HADJMOHAMMADI,M.R.; KAMEL,K.

    2008-01-01

    The chemometrics approach was applied to the optimization of separation of quinolines in micellar liquid tigated by means of multivariate analysis. The factors considered were the concentration of sodium dodecyl sulfate (SDS), the organic modifier concentration and the length of its alkyl chain, and pH of the mobile phase. The ex-periments were performed according to a face centered cube response surface experimental design. In order to op-timize the separation a Pareto-optimality method was employed. The models were verified, because a good agree-ment was observed between the predicted and experimental values of the chromatographic response function in the optimal condition. The obtained regression models were characterized by both descriptive and predictive ability (R2≥0.97 and R2cv≥0.92) and allowed the chromatographic separation of the quinolines with a good resolution and a total analysis time of 50 min.

  18. 7-Chloro-4-[(E-2-(4-methoxybenzylidenehydrazin-1-yl]quinoline monohydrate

    Directory of Open Access Journals (Sweden)

    Edward R. T. Tiekink

    2010-03-01

    Full Text Available The organic molecule in the title hydrate, C17H14ClN3O·H2O, has a small but significant twist from planarity, as seen in the dihedral angle of 12.10 (17° between the quinoline and benzene rings. The conformation about the C=N bond is E. Chains along the b axis are formed in the crystal structure aided by water–quinoline O—H...N (× 2 and hydrazone–water N—H...O hydrogen bonds. Layers of these chains stack along the a axis via C—H...π and π–π interactions [ring centroid–ring centroid distance = 3.674 (2 Å]. C—H...O interactions are also present.

  19. An experimental screen for quinoline/fumaric acid salts and co-crystals

    DEFF Research Database (Denmark)

    Beko, S. L.; Schmidt, M. U.; Bond, A. D.

    2012-01-01

    An experimental screen has been carried out for salts and co-crystals of quinoline (C9H7N) and fumaric acid (C4H4O4), including solution-based co-crystallisation from a variety of solvents, solvent-assisted and solvent-free co-grinding, and direct co-crystallisation of the starting materials....... Characterised products include the previously published 1 : 1 salt, C9H8N+center dot C4H3O4-, and a new 2 : 1 quinoline/fumaric acid co-crystal, (C9H7N)(2)center dot C4H4O4. Attempts to influence the crystallisation outcome by addition of 6-methylquinoline yielded a second co-crystal, also with an inherent 2...

  20. The fate of methanol in anaerobic bioreactors.

    NARCIS (Netherlands)

    Florencio, L.

    1994-01-01

    Methanol is an important component of certain industrial wastewaters. In anaerobic environments, methanol can be utilized by methanogens and acetogens. In wastewater treatment plants, the conversion of methanol into methane is preferred because this conversion is responsible for chemical oxygen dema

  1. Ionic liquid catalyzed convenient synthesis of imidazo[1,2-a]quinoline under sonic condition

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Devji S.; Avalani, Jemin R.; Raval, Dipak K., E-mail: dipanalka@yahoo.com [Department of Chemistry, Sardar Patel University Gujarat (India)

    2012-10-15

    An efficient protocol for the synthesis of imidazo[1,2-a]quinoline from aldehydes, enaminones, and malononitrile using 1,8-diazabicyclo[5.4.0]-undec-7-en-8-ium acetate ([DBU][Ac]) as a catalyst under ultrasound irradiation is described. Compared with other methods, this new method has the advantages of easier work-up, milder reaction conditions, high yields and environmentally benign procedure. (author)

  2. 8-[(3-Phenyl-1,2,4-oxadiazol-5-ylmethoxy]quinoline monohydrate

    Directory of Open Access Journals (Sweden)

    Shu-Yuan Bai

    2013-07-01

    Full Text Available In the title compound, C18H13N3O2·H2O, the oxadiazole ring forms dihedral angles 7.21 (10 and 21.25 (11° with the quinoline and benzene rings, respectively. The crystal structure features O—H...N hydrogen bonds and is further consolidated by C—H...O hydrogen-bonding interactions involving the water molecule of hydration.

  3. Diiodido[methyl 2-(quinolin-8-yloxyacetate-κN]mercury(II

    Directory of Open Access Journals (Sweden)

    Yu-Hong Wang

    2012-08-01

    Full Text Available In the title mononuclear complex, [HgI2(C12H11NO3], the HgII ion has a distorted trigonal–planar coordination sphere defined by two I− anions and the N atom of a methyl 2-(quinolin-8-yloxyacetate ligand. In the crystal, face-to-face π–π stacking interactions, with a centroid–centroid distance of 3.563 (9 Å, are observed.

  4. Nerve growth factor protects cholinergic neurons against quinolinic acid-induced excitotoxicity in wistar rats

    OpenAIRE

    Vasiljević Ivana D.; Jovanović Marina D.; Čolić Miodrag J.; Mićić D.; Ninković Milica; Maličević Živorad

    2004-01-01

    The etiology of neuronal death in neurodegenerative diseases, including Huntington's disease (HD) is still unknown. There could be a complex interplay between altered energy metabolism, excitotoxicity and oxidative stress. Excitotoxic striatal lesions induced by quinolinic acid (QA), were used to test for the neuroprotective actions of nerve growth factor (NGF) on striatal cholinergic and GABAergic neurons. QA is an endogenous excitotoxin acting on N-methyl-D-aspartate (NMDA) rec...

  5. Ring-closure Reaction to Novel Quinoline Derivatives and Their Structural Characterization

    Institute of Scientific and Technical Information of China (English)

    L(U),Yin-Xiang(吕银祥); LAN,Bi-Jian(蓝碧健); ZHOU,Hui(周辉); XU,Wei(徐伟); WANG,Jing-Mei(王静梅); HUANG,Yong-Ming(黄永明)

    2004-01-01

    In the condensation of arylaldehydes with arylethylidenemalononitriles, it was found that, besides the normal product dienes a, the ring-closure product quinoline derivatives b can be also obtained in 26%-50% yields. The substituent effects were also examined and a possible reaction mechanism was proposed for the formation of b. The X-ray crystal structure of 1b confirms the structure of the ring-closure product.

  6. Structure-activity relationship of anti-malarial spongean peroxides having a 3-methoxy-1,2-dioxane structure.

    Science.gov (United States)

    Kawanishi, Motoyuki; Kotoku, Naoyuki; Itagaki, Sawako; Horii, Toshihiro; Kobayashi, Motomasa

    2004-10-15

    In order to study the structure-activity relationship of anti-malarial spongean peroxides, several analogues concerning with the 6-methoxyacetyl moiety and the 3-pentyl residue in methyl 2-(3-methoxy-3-pentyl-1,2-dioxan-6-yl)acetate were synthesized and evaluated for anti-malarial activity. The tert-butyl ester analogue 14 showed stability in mouse serum and a high selectivity index against the malaria parasite, Plasmodium falciparum, and the citronellyl analogue 31 exhibited the strongest in vitro anti-malarial activity among them, and the imidazole analogue 25 showed desirable in vivo anti-malarial activity against P. berghei infected mice. PMID:15388157

  7. Proton reduction by a nickel complex with an internal quinoline moiety for proton relay.

    Science.gov (United States)

    Majee, Karunamay; Patel, Jully; Rai, Surabhi; Das, Babulal; Panda, Binata; Padhi, Sumanta Kumar

    2016-08-21

    The complex Ni(DQPD) (where DQPD = deprotonated N(2),N(6)-di(quinolin-8-yl)pyridine-2,6-dicarboxamide (DQPDH2)) behaves as a visible light driven active catalyst to reduce protons from water when employed with the photosensitizer fluorescein (Fl) and triethylamine (TEA) as the sacrificial electron donor. The photocatalytic system shows very high activity, attaining 2160 turnovers and an initial turnover rate of 0.032 s(-1) with respect to the catalyst. The proposed electrocatalytic mechanism is of the CECE type (C is a chemical step protonation and E is the electrochemical step reduction), where the Ni(DQPD) catalyst undergoes rapid protonation at the non-coordinating nitrogen atom of the quinoline before undergoing reduction. The location of the pendant base is a key factor such that the N-H resulting from the protonation of the non-coordinating nitrogen atom of the quinoline is properly located to interact with the Ni-H hydride leading to heterocoupling between protons and hydrides. Theoretical calculations for the catalytic system were carried out using the density functional level of theory (DFT) and are consistent with a mechanism for catalysis in a polypyridine nickel system. This is the first report of a polypyridine based nickel catalyst where the pendant base is responsible for the internal proton relay towards the metal center through the heterocoupling between protons and hydrides to generate hydrogen. PMID:27432223

  8. Active-site models for complexes of quinolinate synthase with substrates and intermediates

    Energy Technology Data Exchange (ETDEWEB)

    Soriano, Erika V.; Zhang, Yang; Colabroy, Keri L.; Sanders, Jennie M.; Settembre, Ethan C.; Dorrestein, Pieter C.; Begley, Tadhg P.; Ealick, Steven E., E-mail: see3@cornell.edu [Cornell University, Ithaca, NY 14853-1301 (United States)

    2013-09-01

    Structural studies of quinolinate synthase suggest a model for the enzyme–substrate complex and an enzyme–intermediate complex with a [4Fe–4S] cluster. Quinolinate synthase (QS) catalyzes the condensation of iminoaspartate and dihydroxyacetone phosphate to form quinolinate, the universal precursor for the de novo biosynthesis of nicotinamide adenine dinucleotide. QS has been difficult to characterize owing either to instability or lack of activity when it is overexpressed and purified. Here, the structure of QS from Pyrococcus furiosus has been determined at 2.8 Å resolution. The structure is a homodimer consisting of three domains per protomer. Each domain shows the same topology with a four-stranded parallel β-sheet flanked by four α-helices, suggesting that the domains are the result of gene triplication. Biochemical studies of QS indicate that the enzyme requires a [4Fe–4S] cluster, which is lacking in this crystal structure, for full activity. The organization of domains in the protomer is distinctly different from that of a monomeric structure of QS from P. horikoshii [Sakuraba et al. (2005 ▶), J. Biol. Chem.280, 26645–26648]. The domain arrangement in P. furiosus QS may be related to protection of cysteine side chains, which are required to chelate the [4Fe–4S] cluster, prior to cluster assembly.

  9. The direct methanol fuel cell

    Energy Technology Data Exchange (ETDEWEB)

    Halpert, G.; Narayanan, S.R.; Frank, H. [Jet Propulsion Lab., Pasadena, CA (United States)

    1995-08-01

    This presentation describes the approach and progress in the ARPA-sponsored effort to develop a Direct Methanol, Liquid-Feed Fuel Cell (DMLFFC) with a solid Polymer Electrolyte Membrane (PEM) for battery replacement in small portable applications. Using Membrane Electrode Assemblies (MEAs) developed by JPL and Giner, significant voltage was demonstrated at relatively high current densities. The DMLFFC utilizes a 3 percent aqueous solution of methanol that is oxidized directly in the anode (fuel) chamber and oxygen (air) in the cathode chamber to produce water and significant power. The only products are water and CO{sub 2}. The ARPA effort is aimed at replacing the battery in the BA 5590 military radio.

  10. The methanol industry's missed opportunities

    International Nuclear Information System (INIS)

    Throughout its history the methanol industry has been backward in research and development and in industry cooperation on public image and regulatory matters. It has been extremely reticent as to the virtue of its product for new uses, especially for motor fuel. While this is perhaps understandable looking back, it is inexcusable looking forward. The industry needs to cooperate on a worldwide basis in research and market development, on the one hand, and in image-building and political influence, on the other, staying, of course, within the US and European and other regional antitrust regulations. Unless the industry develops the motor fuel market, and especially the exciting new approach through fuel cell operated EVs, to siphon off incremental capacity and keep plants running at 90% or more of capacity, it will continue to live in a price roller-coaster climate. A few low-cost producers will do reasonably well and the rest will just get along or drop out here and there along the way, as in the past. Having come so far from such a humble beginning, it is a shame not to realize the full potential that is clearly there: a potential to nearly double sales dollars without new plants and to produce from a plentiful resource, at least for the next half-century, all the methanol that can be imagined to be needed. Beyond that the industry can turn to renewable energy--the sun--via biomass growth, to make their product. In so doing, it can perhaps apply methanol as a plant growth stimulant, in effect making the product fully self-sustainable. The world needs to know what methanol can do to provide--economically and reliably--the things upon which a better life rests

  11. Withanolide artifacts formed in methanol.

    Science.gov (United States)

    Cao, Cong-Mei; Zhang, Huaping; Gallagher, Robert J; Timmermann, Barbara N

    2013-11-22

    Methanol solutions of the main withanolides (6-8) naturally present in Physalis longifolia yielded five artificial withanolides (1-5), including three new compounds (1-3). Withanolides 1 and 2 were identified as intramolecular Michael addition derivatives, while withanolides 3-5 were the result of intermolecular Michael addition. A comprehensive literature investigation was conducted to identify potential withanolide Michael addition artifacts isolated from Solanaceous species to date.

  12. Compound antimalarial ethosomal cataplasm: preparation, evaluation, and mechanism of penetration enhancement.

    Science.gov (United States)

    Shen, Shuo; Liu, Shu-Zhi; Zhang, Yu-Shi; Du, Mao-Bo; Liang, Ai-Hua; Song, Li-Hua; Ye, Zu-Guang

    2015-01-01

    Malaria is still a serious public health problem in some parts of the world. The problems of recurrence and drug resistance are increasingly more serious. Thus, it is necessary to develop a novel antimalarial agent. The objectives of this study were to construct a novel compound antimalarial transdermal nanosystem-ethosomal cataplasm, to investigate its characteristics and efficiency, and to systematically explore the penetration-enhancing mechanisms of ethosomal cataplasm. Artesunate-loaded ethosomes and febrifugine-loaded ethosomes were prepared, and their characteristics were evaluated. Drug-loaded ethosomes were incorporated in the matrix of cataplasm to form the compound antimalarial ethosomal cataplasm. With the help of ethosomal technology, the accumulated permeation quantity of artesunate significantly increased at 8 hours after administration, which was 1.57 times as much as that of conventional cataplasm. Soon after administration, the ethosomal cataplasm could make a large quantity of antimalarial drug quickly penetrate through skin, then the remaining drug in the ethosomal cataplasm could be steadily released. These characteristics of ethosomal cataplasm are favorable for antimalarial drugs to kill Plasmodium spp. quickly and prevent the resurgence of Plasmodium spp. As expected, the ethosomal cataplasm showed good antimalarial efficiency in this experiment. The negative conversion rates were 100% and the recurrence rates were 0% at all dosages. The mechanism of penetration enhancement of the ethosomal cataplasm was systematically explored using an optics microscope, polarization microscope, and transmission electron microscopy. The microstructure, ultrastructure, and birefringent structure in skin were observed. Data obtained in this study showed that the application of ethosomal technology to antimalarial cataplasm could improve the transdermal delivery of drug, enhance the efficacy, and facilitate practical application in clinic. PMID:26170661

  13. Compound antimalarial ethosomal cataplasm: preparation, evaluation, and mechanism of penetration enhancement.

    Science.gov (United States)

    Shen, Shuo; Liu, Shu-Zhi; Zhang, Yu-Shi; Du, Mao-Bo; Liang, Ai-Hua; Song, Li-Hua; Ye, Zu-Guang

    2015-01-01

    Malaria is still a serious public health problem in some parts of the world. The problems of recurrence and drug resistance are increasingly more serious. Thus, it is necessary to develop a novel antimalarial agent. The objectives of this study were to construct a novel compound antimalarial transdermal nanosystem-ethosomal cataplasm, to investigate its characteristics and efficiency, and to systematically explore the penetration-enhancing mechanisms of ethosomal cataplasm. Artesunate-loaded ethosomes and febrifugine-loaded ethosomes were prepared, and their characteristics were evaluated. Drug-loaded ethosomes were incorporated in the matrix of cataplasm to form the compound antimalarial ethosomal cataplasm. With the help of ethosomal technology, the accumulated permeation quantity of artesunate significantly increased at 8 hours after administration, which was 1.57 times as much as that of conventional cataplasm. Soon after administration, the ethosomal cataplasm could make a large quantity of antimalarial drug quickly penetrate through skin, then the remaining drug in the ethosomal cataplasm could be steadily released. These characteristics of ethosomal cataplasm are favorable for antimalarial drugs to kill Plasmodium spp. quickly and prevent the resurgence of Plasmodium spp. As expected, the ethosomal cataplasm showed good antimalarial efficiency in this experiment. The negative conversion rates were 100% and the recurrence rates were 0% at all dosages. The mechanism of penetration enhancement of the ethosomal cataplasm was systematically explored using an optics microscope, polarization microscope, and transmission electron microscopy. The microstructure, ultrastructure, and birefringent structure in skin were observed. Data obtained in this study showed that the application of ethosomal technology to antimalarial cataplasm could improve the transdermal delivery of drug, enhance the efficacy, and facilitate practical application in clinic.

  14. Excited-state intramolecular proton transfer (ESIPT) inspired azole-quinoline based fluorophores: Synthesis and photophysical properties study

    Energy Technology Data Exchange (ETDEWEB)

    Padalkar, Vikas S.; Sekar, Nagaiyan, E-mail: n.sekar@ictmumbai.edu.in

    2014-11-15

    7-Hydroxy-3-(4-nitrophenyl)quinoline-6-carboxylic acid was obtained by the condensation reaction of p-amino salicylic acid and 4-nitrophenylmalonadialdehyde which was obtained from phenylacetonitrile through nitration, hydrolysis and Vilsmeier reaction. 7-Hydroxy-3-(4-nitrophenyl) quinoline-6-carboxylic acid was condensed with different o-aminophenols or o-aminothiophenol in ethanol in the presence of phosphorustrichloride. Synthesized quinoline contained benzimidazole and benzothiazole moieties. Photophysical behaviors of these compounds in solvents of different polarities were studied using UV–vis and fluorescence spectroscopy. The compounds showed single absorption in all the studied solvents. The dual emissions (normal emission and ESIPT emission) as well as large Stokes' shift emission pattern were observed for the synthesized fluorophores. The photophysical study shows that the emission properties of the compounds depend on the solvent polarity. The photophysical properties of the compounds were compared with structurally analogous ESIPT quinoline. Thermal stability of the compounds was studied using thermogravimetric analysis and results show that compounds are thermally stable up to 300 °C. The synthesized quinoline derivatives were characterized using elemental analysis, FT-IR and {sup 1}H –NMR, {sup 13}C –NMR spectroscopy and mass spectral analysis. - Highlights: • First and unique study of quinoline derivatives contain ESIPT azole unit at 6-position and hydroxyl group at 7-position. • Compounds are fluorescent with considerable quantum yields. • All compounds showed absorption in ultraviolet region and emission in visible region with large Stokes' shift. • The photophysical properties of new compounds were compared with reported ESIPT quinoline analogous.

  15. Studies on methanol - oxidizing yeast. III. Enzyme.

    Science.gov (United States)

    Volfová, O

    1975-01-01

    Oxidation of methanol, formaldehyde and formic acid was studied in cells and cell-free extract of the yeast Candida boidinii No. 11Bh. Methanol oxidase, an enzyme oxidizing methanol to formaldehyde, was formed inducibly after the addition of methanol to yeast cells. The oxidation of methanol by cell-free extract was dependent on the presence of oxygen and independent of any addition of nicotine-amide nucleotides. Temperature optimum for the oxidation of methanol to formaldehyde was 35 degrees C, pH optimum was 8.5. The Km for methanol was 0.8mM. The cell-free extract exhibited a broad substrate specificity towards primary alcohols (C1--C6). The activity of methanol oxidase was not inhibited by 1mM KCN, EDTA or monoiodoacetic acid. The strongest inhibitory action was exerted by p-chloromercuribenzoate. Both the cells and the cell-free extract contained catalase which participated in the oxidation of methanol to formaldehyde; the enzyme was constitutively formed by the yeast. The pH optimum for the degradation of H2O2 was in the same range as the optimum for methanol oxidation, viz. at 8.5. Catalase was more resistant to high pH than methanol oxidase. The cell-free extract contained also GSH-dependent NAD-formaldehyde dehydrogenase with Km = 0.29mM and NAD-formate dehydrogenase with Km = 55mM. PMID:240764

  16. Perspective for the production of antimalarial drugs in Brazil.

    Science.gov (United States)

    Gilbert, B

    1992-01-01

    There appears to be no chemical manufacture of antimalarial drugs in Brazil. Technology at the laboratory process level has been developed for chloroquine, mefloquine, pyrimethamine and cycloguanil, but not perfected nor scaled-up, largely for economic reasons and market uncertainty. Development of primaquine has been contracted but it will run into the same difficulty. Manufacturing capacity for sulfadoxine was registered in the SDI by Roche. A project to produce artemisinine and its derivatives is under way at UNICAMP-CPQBA but is hampered by low content in the plant. Proguanil could be produced easily, but apparently no attempt has been made to do so. Quinine is imported on a large scale mostly for soft-drink production. Since malarial treatment falls largely within the responsibility of the Government health authorities, manufacture of drugs in Brazil will depend on an assured medium-term purchase order made to a potential local manufacturer, since competition in the world market is scarcely viable at the present moment.

  17. Study of antimalarial activity of chemical constituents from Diospyros quaesita.

    Science.gov (United States)

    Ma, Cui-Ying; Musoke, Sebisubi Fred; Tan, Ghee Teng; Sydara, Kongmany; Bouamanivong, Somsanith; Southavong, Bounhoong; Soejarto, D Doel; Fong, Harry H S; Zhang, Hong-Jie

    2008-11-01

    Bioassay-directed fractionation led to the isolation of seven compounds from a sample of the dried leaves, twigs, and branches of Diospyros quaesita Thw. (Ebenaceae). One of the isolates, betulinic acid 3-caffeate (1), showed in vitro antimalarial activity against Plasmodium falciparum clones D(6) (chloroquine-sensitive) and W(2) (chloroquine-resistant) with IC(50) values of 1.40 and 0.98 microM, respectively. Evaluation of compound 1 in the human oral epidermoid (KB) cancer cell line revealed cytotoxicity at ED(50) of 4.0 microM. In an attempt to reduce the cytotoxicity of 1, the acetylated derivative 1a and betulinic acid (1b) were prepared. Of the seven isolates, diospyrosin (2) was determined to be a new neolignan. In addition to 1, other known compounds isolated in this study were pinoresinol, lariciresinol, N-benzoyl-L-phenylalaninol, scopoletin, and poriferast-5-en-3beta,7alpha-diol. The structure of 2 was elucidated based on spectroscopic data analysis including 1D- and 2D-NMR, and HR-ESI-MS. PMID:19035573

  18. Targeting histone deacetylase inhibitors for anti-malarial therapy.

    Science.gov (United States)

    Andrews, Katherine T; Tran, Thanh N; Wheatley, Nicole C; Fairlie, David P

    2009-01-01

    It is now clear that histone acetylation plays key roles in regulating gene transcription in both eukaryotes and prokaryotes, the acetylated form inducing gene expression while deacetylation silences genes. Recent studies have identified roles for histone acetyltransferases (HATs) and/or histone deacetylases (HDACs) in a number of parasites including Entamoeba histolytica, Toxoplasma gondii, Schistosoma mansoni, Cryptosporidium sp., Leishmania donovani, Neospora caninum, and Plasmodium falciparum. Here we survey fairly limited efforts to date in profiling antimalarial activities of HDAC inhibitors, showing that such compounds are potent inhibitors of the growth of P. falciparum in vitro and in vivo. Most of the compounds evaluated so far have borne a zinc-binding hydroxamate group that tends to be metabolized in vivo, and thus new zinc-binding groups need to be incorporated into second generation inhibitors in order to mask the catalytic zinc in the active site of HDACs. Also the development of compounds that are selective for parasitic HDACs over mammalian HDACs is still in relative infancy and it will take some time to derive antiparasitic HDAC inhibitor compounds with minimal toxicity for the host and acceptable pharmacokinetic and pharmacodynamic profiles for human treatment. Nevertheless, results to date suggest that HDAC inhibitor development represents a promising new approach to the potential treatment of parasitic infections, including those induced by malaria protozoa, and may offer new therapeutic targets within increasingly drug-resistant malarial parasites. PMID:19355992

  19. Targeting protein kinases in the malaria parasite: update of an antimalarial drug target.

    Science.gov (United States)

    Zhang, Veronica M; Chavchich, Marina; Waters, Norman C

    2012-01-01

    Millions of deaths each year are attributed to malaria worldwide. Transmitted through the bite of an Anopheles mosquito, infection and subsequent death from the Plasmodium species, most notably P. falciparum, can readily spread through a susceptible population. A malaria vaccine does not exist and resistance to virtually every antimalarial drug predicts that mortality and morbidity associated with this disease will increase. With only a few antimalarial drugs currently in the pipeline, new therapeutic options and novel chemotypes are desperately needed. Hit-to-Lead diversity may successfully provide novel inhibitory scaffolds when essential enzymes are targeted, for example, the plasmodial protein kinases. Throughout the entire life cycle of the malaria parasite, protein kinases are essential for growth and development. Ongoing efforts continue to characterize these kinases, while simultaneously pursuing them as antimalarial drug targets. A collection of structural data, inhibitory profiles and target validation has set the foundation and support for targeting the malarial kinome. Pursuing protein kinases as cancer drug targets has generated a wealth of information on the inhibitory strategies that can be useful for antimalarial drug discovery. In this review, progress on selected protein kinases is described. As the search for novel antimalarials continues, an understanding of the phosphor-regulatory pathways will not only validate protein kinase targets, but also will identify novel chemotypes to thwart malaria drug resistance. PMID:22242850

  20. Public Awareness and Identification of Counterfeit Drugs in Tanzania: A View on Antimalarial Drugs

    Directory of Open Access Journals (Sweden)

    Linus Mhando

    2016-01-01

    Full Text Available Background. The illicit trade in counterfeit antimalarial drugs is a major setback to the fight against malaria. Information on public awareness and ability to identify counterfeit drugs is scanty. Aim. Therefore, the present study aimed at assessing public awareness and the ability to identify counterfeit antimalarial drugs based on simple observations such as appearance of the drugs, packaging, labelling, and leaflets. Methodology. A cross-sectional study was conducted using interviewer administered structured questionnaire and a checklist. Respondents were required to spot the difference between genuine and counterfeit antimalarial drugs given to them. Data was analysed using SPSS version 20. Results. The majority of respondents, 163 (55.6%, were able to distinguish between genuine and counterfeit antimalarial drugs. Respondents with knowledge on health effects of counterfeit drugs were more likely to identify genuine and counterfeit drugs than their counterparts (P=0.003; OR = 2.95; 95% CI: 1.47–5.65. The majority of respondents, 190 (64.8%, perceived the presence of counterfeit drugs to be a big problem to the community. Conclusions. A substantial proportion of respondents were able to distinguish between genuine and counterfeit antimalarial drugs. Public empowerment in identifying counterfeit drugs by simple observations is a major step towards discouraging the market of counterfeit drugs.

  1. Quinoline-degrading strain Pseudomonas aeruginosa KDQ4 isolated from coking activated sludge is capable of the simultaneous removal of phenol in a dual substrate system.

    Science.gov (United States)

    Zhang, Panhong; Jia, Rong; Zhang, Yuxiu; Shi, Peili; Chai, Tuanyao

    2016-11-01

    Quinoline is a refractory organic compound in the treatment of coking wastewater. The isolation of high efficiency quinoline-degrading bacteria from activated sludge and the evaluation of their degradation characteristics in the presence of phenol or in the actual coking wastewater are important for the improvement of effluent quality. The novel bacterial strain Pseudomonas aeruginosa KDQ4 was isolated from a quinoline enrichment culture obtained from the activated sludge of a coking wastewater treatment plant. The optimum temperature and initial pH for quinoline degradation were 33-38°C and 8-9, respectively. KDQ4 completely degraded 400 mg/L of quinoline within 24 h and 800 mg/L of phenol within 30 h. In the dual-substrate system, the removal efficiencies of quinoline and phenol at the same initial concentration (200 mg/L) by KDQ4 were 89% and 100% within 24 h, respectively, indicating that KDQ4 could simultaneously and quickly degrade quinoline and phenol in a coexistence system. Moreover, KDQ4 was able to adapt to actual coking wastewater containing high quinoline and phenol concentrations and rapidly remove them. KDQ4 also exhibited heterotrophic nitrification and aerobic denitrification potential under aerobic conditions. These results suggested a potential bioaugmentation role for KDQ4 in the removal of nitrogen-heterocyclic compounds and phenolics from coking wastewater. PMID:27458688

  2. Towards a methanol economy based on homogeneous catalysis: methanol to H2 and CO2 to methanol.

    Science.gov (United States)

    Alberico, E; Nielsen, M

    2015-04-21

    The possibility to implement both the exhaustive dehydrogenation of aqueous methanol to hydrogen and CO2 and the reverse reaction, the hydrogenation of CO2 to methanol and water, may pave the way to a methanol based economy as part of a promising renewable energy system. Recently, homogeneous catalytic systems have been reported which are able to promote either one or the other of the two reactions under mild conditions. Here, we review and discuss these developments.

  3. Synthesis of 5-iodopyrrolo[1,2-a]quinolines and indolo[1,2-a]quinolines via iodine-mediated electrophilic and regioselective 6-endo-dig ring closure.

    Science.gov (United States)

    Verma, Akhilesh Kumar; Shukla, Satya Prakash; Singh, Jaspal; Rustagi, Vineeta

    2011-07-15

    The endo-cyclic ring closure of 1-(2-(substituted ethynyl)phenyl)-1H-pyrroles 3a-t and 1-(2-(substituted ethynyl)phenyl)-H-indole 4a-o mediated by Lewis acid (I(2)) under mild conditions afforded substituted 5-iodopyrrolo[1,2-a]quinolines 5a-t and 5-iodoindolo[1,2-a]quinolines 6a-o in good to excellent yields. The reaction shows selective C-C bond formation on the more electrophilic alkynyl carbon, resulting in the regioselective 6-endo-dig-cyclized product. Iodo derivatives of pyrrolo- and indoloquinolines allow functional group diversification on the quinoline nucleus, which proves to be highly advantageous for structural and biological activity assessments.

  4. Monitoring the efficacy of antimalarial medicines in India via sentinel sites: Outcomes and risk factors for treatment failure

    Directory of Open Access Journals (Sweden)

    Neelima Mishra

    2016-01-01

    Interpretation & conclusion: Till 2012, India′s national antimalarial drug resistance monitoring system proved highly efficacious and safe towards first-line antimalarials used in the country, except in Northeastern region where a decline in efficacy of AS+SP has been observed. This led to change in first-line treatment for P. falciparum to artemether-lumefantrine in Northeastern region.

  5. Collaborative health and enforcement operations on the quality of antimalarials and antibiotics in southeast Asia.

    Science.gov (United States)

    Yong, Yuk Lin; Plançon, Aline; Lau, Yen Hui; Hostetler, Dana M; Fernández, Facundo M; Green, Michael D; Sounvoravong, Sourisak; Nara, Suon; Boravann, Mam; Dumrong, Thitikornkovit; Bangsawan, Nurjaya; Low, Min Yong; Lim, Chin-Chin; Ai, Ruth Lee Choo; Newton, Paul N

    2015-06-01

    Counterfeit (or falsified) and substandard medicines pose a major public health risk. We describe the findings of Operation Storm I and II conducted in 2008-2009 to combat counterfeit medicines through partnership between national customs, Drug Regulatory Agencies (DRAs), and police in Cambodia, Indonesia, Laos, Myanmar, Singapore, Thailand, and Vietnam. Samples were obtained from seizures and market surveillance by national DRAs. Laboratory analysis using spectroscopic and chromatographic techniques and examination of packaging were performed. Ninety-three suspect antibiotics and 95 antimalarial samples were collected. Of the 93 antibiotics, 29 (31%) had % active pharmaceutical ingredient content (%API) 115% (including one counterfeit). Of the 95 antimalarials, 30 (32%) had %API 115% API (including one counterfeit). A significant minority of samples, antimalarials (13%) and antibiotics (15%), were collected in plastic bags with minimal or no labeling. Of 20 ampicillin samples, 13 (65%) contained medicines. PMID:25897069

  6. Blood schizontocidal activity of methylene blue in combination with antimalarials against Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Garavito G.

    2007-06-01

    Full Text Available Methylene blue (MB is the oldest synthetic antimalarial. It is not used anymore as antimalarial but should be reconsidered. For this purpose we have measured its impact on both chloroquine sensitive and resistant Plasmodium strains. We showed that around 5 nM of MB were able to inhibit 50% of the parasite growth in vitro and that late rings and early trophozoites were the most sensitive stages; while early rings, late trophozoites and schizonts were less sensitive. Drug interaction study following fractional inhibitory concentrations (FIC method showed antagonism with amodiaquine, atovaquone, doxycycline, pyrimethamine; additivity with artemether, chloroquine, mefloquine, primaquine and synergy with quinine. These results confirmed the interest of MB that could be integrated in a new low cost antimalarial combination therapy.

  7. Influence of smoking on disease severity and antimalarial therapy in cutaneous lupus erythematosus

    DEFF Research Database (Denmark)

    Kuhn, A; Sigges, J; Biazar, C;

    2014-01-01

    BACKGROUND: In recent years it has been controversially discussed in the literature if smoking is associated with the activity of cutaneous lupus erythematosus (CLE) and the efficacy of antimalarial agents. OBJECTIVES: To investigate the influence of smoking on disease severity and antimalarial...... treatment in patients with CLE using the Core Set Questionnaire of the European Society of Cutaneous Lupus Erythematosus (EUSCLE). METHODS: A total of 1002 patients (768 female, 234 male) with different CLE subtypes were included in this cross-sectional study, which was performed in 14 different countries....... Smoking behaviour was assessed by the EUSCLE Core Set Questionnaire in 838 patients and statistically analysed using an SPSS database. The results were correlated with the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the efficacy of antimalarial treatment. RESULTS: A high...

  8. Screening for antimalarial and acetylcholinesterase inhibitory activities of some Iranian seaweeds.

    Science.gov (United States)

    Ghannadi, A; Plubrukarn, A; Zandi, K; Sartavi, K; Yegdaneh, A

    2013-04-01

    Alcoholic extracts of 8 different types of seaweeds from Iran's Persian Gulf were tested for their antimalarial and acetylcholinesterase enzyme (AChE) inhibitory activities for the first time. A modified Ellman and Ingkaninan method was used for measuring AChE inhibitory activity in which galanthamine was used as the reference. The antimalarial assay was performed using microculture radioisotope technique. Mefloquine and dihydroartemisinin were uased as the standards. The extract of Sargassum boveanum (Sargasseae family) showed the highest AChE inhibitory activity (IC50 equals to 1 mg ml(-1)) while Cystoseira indica (Cystoseiraceae family) exhibited the least activity (IC50 of 11 mg ml(-1)). The species from Rhodophyta (Gracilaria corticata and Gracilaria salicornia) also showed moderate activities (IC509.5, 8.7 mg ml(-1), respectively). All extracts were inactive in antimalarial assay. PMID:24019820

  9. Propane Clathrate Hydrate Formation Accelerated by Methanol.

    Science.gov (United States)

    Amtawong, Jaruwan; Guo, Jin; Hale, Jared S; Sengupta, Suvrajit; Fleischer, Everly B; Martin, Rachel W; Janda, Kenneth C

    2016-07-01

    The role of methanol as both an inhibitor and a catalyst for the formation of clathrate hydrates (CHs) has been a topic of intense study. We report a new quantitative study of the kinetics of propane CH formation at 253 K from the reaction of propane gas with ice particles that have been doped with varying amounts of methanol. We find that methanol significantly accelerates the formation reaction with quite small doping quantities. Even for only 1 methanol molecule per 10 000 water molecules, the maximum uptake rate of propane into CHs is enhanced and the initiation pressure is reduced. These results enable more efficient production of CHs for gas storage. This remarkable acceleration of the CH formation reaction by small quantities of methanol may place constraints on the mechanism of the inhibition effect observed under other conditions, usually employing much larger quantities of methanol. PMID:27275862

  10. (Benzoato-κ2O,O′(quinoline-2-carboxylato-κ2N,O(quinoline-2-carboxylic acid-κ2N,Omanganese(II

    Directory of Open Access Journals (Sweden)

    Nuno D. Martins

    2008-01-01

    Full Text Available The crystal structure of the title compound, [Mn(C7H5O2(C10H6NO2(C10H7NO2], contains manganese(II ions six-coordinated in a distorted octahedral environment. The equatorial plane is occupied by four O atoms, two from the carboxylate group of the benzoate ion, the other two from carboxylate/carboxyl groups of the quinaldate/quinaldic acid molecules. The axial positions are occupied by the N atoms of the quinoline ring systems. The metal ion lies on a twofold rotation axis that bisects the benzoate ligand; the quinaldate and quinaldic acid ligands are therefore equivalent by symmetry, and the carboxylate/carboxyl groups are disordered. The complexes are joined together by hydrogen bonds between the carboxylate/carboxyl groups of adjacent quinaldate/quinaldic acid molecules, forming zigzag chains that run along the c axis.

  11. Efficient example of cross-linked polymeric catalysed synthesis of 7-benzo[ℎ]indeno[1,2-]quinolin-8-one and 8-naphtho[2,3-ℎ]indeno[1,2-]quinolin-9-one

    Indian Academy of Sciences (India)

    Reza Sandaroos; Mehdi Vadi; Saman Damavandi

    2013-11-01

    Cross-linked poly(2-acrylamido-2-methyl propane sulphonic acid) (AMPS) was found to be an efficient heterogeneous catalyst for direct synthesis of 7-benzo[ℎ]indeno[1, 2-]quinolin-8-one and 8-naphtho[2, 3-ℎ]indeno[1, 2-]quinolin-9-one derivatives through one-pot condensation of aromatic aldehydes, 1, 3-indandione and 1-naphthylamine or 1-antharacylamine. The catalyst could be recovered conveniently and reused without any loss of activity. Mild conditions, short reaction times, simplicity, easy workup, and good to excellent yields can be mentioned as the advantages of this research.

  12. Experimental and quantum chemical studies on corrosion inhibition performance of quinoline derivatives for MS in 1N HCl

    Indian Academy of Sciences (India)

    B M Mistry; N S Patel; S Sahoo; S Jauhari

    2012-06-01

    The corrosion inhibition effect of two quinoline derivatives, viz. 2-chloro quinoline 3-carbaldehyde (CQC) and (2-chloro-quinoline-3ylmethyl)--tolyl-amine (CQA) have been investigated against mild steel (MS) in 1N HCl solution using conventional weight loss, potentiodynamic polarization, linear polarization and electrochemical impedance spectroscopy. The losses in weights of MS samples have proved that both CQC and CQA are efficient inhibitors of corrosion. The mixed mode of inhibition was confirmed by electrochemical polarizations. The results of electrochemical impedance spectroscopy have showed changes in the impedance parameters like charge transfer resistance and double-layer capacitance that confirmed strong adsorption of inhibitors on the MS surface. The inhibition action of these compounds was assumed to occur via adsorption on the steel surface through the active centres contained in the molecules. Furthermore, quantum chemical calculations have been performed at B3LYP/6-31G( , ) level to complement the experimental evidence.

  13. Polyamine quinoline rhodium complexes: synthesis and pharmacological evaluation as antiparasitic agents against Plasmodium falciparum and Trichomonas vaginalis.

    Science.gov (United States)

    Stringer, Tameryn; Taylor, Dale; Guzgay, Hajira; Shokar, Ajit; Au, Aaron; Smith, Peter J; Hendricks, Denver T; Land, Kirkwood M; Egan, Timothy J; Smith, Gregory S

    2015-09-01

    A series of mono- and bis-salicylaldimine ligands and their corresponding Rh(i) complexes were prepared. The compounds were characterised using standard spectroscopic techniques including NMR, IR spectroscopy and mass spectrometry. The salicylaldimine ligands and complexes were screened for antiparasitic activity against two strains of Plasmodium falciparum i.e. the NF54 CQ-sensitive and K1 CQ-resistant strain as well as against the G3 isolate of Trichomonas vaginalis. The monomeric salicylaldimine quinolines exhibited good activity against the NF54 strain and the dimeric salicylaldimine quinolines exhibited no cross resistance across the two strains. The binuclear 5-chloro Rh(i) complex displayed the best activity against the Trichomonas vaginalis parasite, possibly a consequence of its enhanced lipophilicity. The compounds were also screened for cytotoxicity in vitro against WHCO1 oesophageal cancer cells. The monomeric salicylaldimine quinolines exhibited high selectivity towards malaria parasites compared to cancer cells, while the dimeric compounds were less selective.

  14. Analysis of denitrifier community in a bioaugmented sequencing batch reactor for the treatment of coking wastewater containing pyridine and quinoline

    Energy Technology Data Exchange (ETDEWEB)

    Bai, Yaohui; Xing, Rui; Wen, Donghui; Tang, Xiaoyan [Peking Univ., Beijing (CN). Key Lab. of Water and Sediment Sciences (Ministry of Education); Sun, Qinghua [Peking Univ., Beijing (CN). Key Lab. of Water and Sediment Sciences (Ministry of Education); Chinese Center for Disease Control and Prevention, Beijing (China). Inst. of Environmental Health and Related Product Safety

    2011-05-15

    The denitrifier community and associated nitrate and nitrite reduction in the bioaugmented and general sequencing batch reactors (SBRs) during the treatment of coking wastewater containing pyridine and quinoline were investigated. The efficiency and stability of nitrate and nitrite reduction in SBR was considerably improved after inoculation with four pyridine- or quinoline-degrading bacterial strains (including three denitrifying strains). Terminal restriction fragment length polymorphism (T-RFLP) based on the nosZ gene revealed that the structures of the denitrifier communities in bioaugmented and non-bioaugmented reactors were distinct and varied during the course of the experiment. Bioaugmentation protected indigenous denitrifiers from disruptions caused by pyridine and quinoline. Clone library analysis showed that one of the added denitrifiers comprised approximately 6% of the denitrifier population in the bioaugmented sludge. (orig.)

  15. Quinoline alkaloids and friedelane-type triterpenes isolated from leaves and wood of Esenbeckia alata Kunt (Rutaceae)

    Energy Technology Data Exchange (ETDEWEB)

    Cuca-Suarez, Luis Enrique; Barrera, Ericsson David Coy [Universidad Nacional de Colombia, Bogota (Colombia). Dept. de Quimica; Alvarez Caballero, Juan Manuel [Universidad del Magdalena, Santa Marta DTCH (Colombia). Facultad de Ciencias Basicas

    2011-07-01

    This work describes the phytochemical exploration of the ethanol extract from leaves and wood of Esenbeckia alata, leading to the isolation and identification of quinoline alkaloids 4-methoxy-3-(3'-methyl-but-2'-enyl)-N-methyl-quinolin-2(1 H)-one, N-methylflindersine, dictamine, kokusaginine, G-fagarine, flindersiamine, as well as the fridelane-type triterpenes, frideline, fridelanol and its acetate derivative. Identification of these compounds was based on full analyses of spectroscopic data ({sup 1}H, {sup 13}C, {sup 1}D, {sup 2}D, IR, MS) and comparison with data reported in literature. Compound 4-methoxy-3-(3'-methyl-but-2'-enyl)-N-methyl-quinolin-2(1 H)-one is reported for the first time for the genus Esenbeckia. (author)

  16. Monitoring antimalarial safety and tolerability in clinical trials: A case study from Uganda

    Directory of Open Access Journals (Sweden)

    Mpimbaza Arthur

    2008-06-01

    Full Text Available Abstract Background New antimalarial regimens, including artemisinin-based combination therapies (ACTs, have been adopted widely as first-line treatment for uncomplicated malaria. Although these drugs appear to be safe and well-tolerated, experience with their use in Africa is limited and continued assessment of safety is a priority. However, no standardized guidelines for evaluating drug safety and tolerability in malaria studies exist. A system for monitoring adverse events in antimalarial trials conducted in Uganda was developed. Here the reporting system is described, and difficulties faced in analysing and interpreting the safety results are illustrated, using data from the trials. Case description Between 2002 and 2007, eleven randomized, controlled clinical trials were conducted to compare the efficacy, safety, and tolerability of different antimalarial regimens for treatment of uncomplicated malaria in Uganda. The approach to adverse event monitoring was similar in all studies. A total of 5,614 treatments were evaluated in 4,876 patients. Differences in baseline characteristics and patterns of adverse event reporting were noted between the sites, which limited the ability to pool and analyse data. Clinical failure following antimalarial treatment confounded associations between treatment and adverse events that were also common symptoms of malaria, particularly in areas of lower transmission intensity. Discussion and evaluation Despite prospectively evaluating for adverse events, limitations in the monitoring system were identified. New standardized guidelines for monitoring safety and tolerability in antimalarial trials are needed, which should address how to detect events of greatest importance, including serious events, those with a causal relationship to the treatment, those which impact on adherence, and events not previously reported. Conclusion Although the World Health Organization has supported the development of

  17. A new in vivo screening paradigm to accelerate antimalarial drug discovery.

    Directory of Open Access Journals (Sweden)

    María Belén Jiménez-Díaz

    Full Text Available The emergence of resistance to available antimalarials requires the urgent development of new medicines. The recent disclosure of several thousand compounds active in vitro against the erythrocyte stage of Plasmodium falciparum has been a major breakthrough, though converting these hits into new medicines challenges current strategies. A new in vivo screening concept was evaluated as a strategy to increase the speed and efficiency of drug discovery projects in malaria. The new in vivo screening concept was developed based on human disease parameters, i.e. parasitemia in the peripheral blood of patients on hospital admission and parasite reduction ratio (PRR, which were allometrically down-scaled into P. berghei-infected mice. Mice with an initial parasitemia (P0 of 1.5% were treated orally for two consecutive days and parasitemia measured 24 h after the second dose. The assay was optimized for detection of compounds able to stop parasite replication (PRR = 1 or induce parasite clearance (PRR >1 with statistical power >99% using only two mice per experimental group. In the P. berghei in vivo screening assay, the PRR of a set of eleven antimalarials with different mechanisms of action correlated with human-equivalent data. Subsequently, 590 compounds from the Tres Cantos Antimalarial Set with activity in vitro against P. falciparum were tested at 50 mg/kg (orally in an assay format that allowed the evaluation of hundreds of compounds per month. The rate of compounds with detectable efficacy was 11.2% and about one third of active compounds showed in vivo efficacy comparable with the most potent antimalarials used clinically. High-throughput, high-content in vivo screening could rapidly select new compounds, dramatically speeding up the discovery of new antimalarial medicines. A global multilateral collaborative project aimed at screening the significant chemical diversity within the antimalarial in vitro hits described in the literature is a

  18. Investigation of Traditional Palestinian Medicinal Plant Inula viscosa as Potential Anti-malarial Agent

    Directory of Open Access Journals (Sweden)

    M. Akkawi

    2014-10-01

    Full Text Available Malaria is a life threatening parasitic disease which is prevalent mainly in developing countries; it is the main cause of global mortality and morbidity. Development and search of novel and effective anti-malarial agents to overcome chloroquine resistance have become a very important issue. Most anti-malarial drugs target the erythrocytic stage of malaria infection, where hemozoin synthesis takes place and is considered a crucial process for the parasite survival. Throughout last decades, natural products have been a significant source of chemotherapeutics especially against malaria. Inula viscosa, Inula viscosa , is a shrub that grows around the Mediterranean basin and considered as an important Palestinian traditional medicinal herb. In this research it was found that the Palestinian flora Inula viscosa alcoholic extract has a significant and promising anti-malarial effect in both in vitro and in vivo systems. The crude alcoholic extract of Inula viscosa has the capability to impede the formation of &beta-hematin in vitro; with an efficiency of about 93% when compared to the standard chloroquine which gave 94% at comparable concentrations. in vivo studies showed that this crude extract inhibited the growth of Plasmodium parasites in the red blood cells at a rate of about 96.6%, with an EC50 value of 0.55 ng/mL. Several secondary plant metabolites may be responsible for this anti-malarial activity; the effect also may be most probably due to the presence of high concentrations of nerolidol which has often been found at high concentrationsin this plant. Nerolidol shows a stronger inhibition of hypoxanthine incorporation than quinine. Its anti-malarial effect is potentiated by other essential oils. Nerolidol is also found in several Artemisia species and in Cymbopogon citratus (lemongrass and Virola surinamensis, all plants known for their anti-malarial properties.

  19. Catalytic conversion of methanol to light olefins

    Energy Technology Data Exchange (ETDEWEB)

    Lee, C.S.; Stead, G.E.

    1987-05-12

    A process is described for converting a methanol-containing feed to an olefin-containing hydrocarbon product having a propylene-methylene weight ratio of at least 35.1:6.4. The process comprises contacting the methanol-containing feed in a reaction zone under methanol conversion conditions with a ZSM-12 zeolite catalyst modified by incorporation of a minor amount of a modifier selected from magnesium oxide, manganese oxide and a combination of both magnesium oxide and manganese oxide.

  20. UO2 production process with methanol washing

    International Nuclear Information System (INIS)

    The invention refers to a process for the recovery of methanol used for washing the ammonium uranyl carbonate obtained during UO2 production. The methanol contains about 50% H2O, about 10% (NH4)2CO3, and is radioactive. According to the invention the methanol is purified at reduced pressure in a distillation unit and then led back to the washing unit. (UWI) 891 HP/UWI 892 MBE

  1. Design configurations of the methanol synthesis loop

    OpenAIRE

    Bøhn, Kristian

    2011-01-01

    In recent years the chemical industry has undergone considerable changes due to increased environmental regulations and energy costs. This master thesis has evaluated three different design considerations of the methanol synthesis loop using Honeywell's general purpose process simulator UniSim Design (R380 Build 14027) combined with MathWorks programming language MATLAB. The three configurations are Lurgis methanol reactor loop as built on Tjeldbergodden, the use of interstage methanol remova...

  2. The ACTwatch project: methods to describe anti-malarial markets in seven countries

    Directory of Open Access Journals (Sweden)

    Chapman Steven

    2011-10-01

    Full Text Available Abstract Background Policy makers, governments and donors are faced with an information gap when considering ways to improve access to artemisinin-based combination therapy (ACT and malaria diagnostics including rapid diagnostic tests (RDTs. To help address some of these gaps, a five-year multi-country research project called ACTwatch was launched. The project is designed to provide a comprehensive picture of the anti-malarial market to inform national and international anti-malarial drug policy decision-making. Methods The project is being conducted in seven malaria-endemic countries: Benin, Cambodia, the Democratic Republic of Congo, Madagascar, Nigeria, Uganda and Zambia from 2008 to 2012. ACTwatch measures which anti-malarials are available, where they are available and at what price and who they are used by. These indicators are measured over time and across countries through three study components: outlet surveys, supply chain studies and household surveys. Nationally representative outlet surveys examine the market share of different anti-malarials passing through public facilities and private retail outlets. Supply chain research provides a picture of the supply chain serving drug outlets, and measures mark-ups at each supply chain level. On the demand side, nationally representative household surveys capture treatment seeking patterns and use of anti-malarial drugs, as well as respondent knowledge of anti-malarials. Discussion The research project provides findings on both the demand and supply side determinants of anti-malarial access. There are four key features of ACTwatch. First is the overlap of the three study components where nationally representative data are collected over similar periods, using a common sampling approach. A second feature is the number and diversity of countries that are studied which allows for cross-country comparisons. Another distinguishing feature is its ability to measure trends over time. Finally, the

  3. Synthesis and antimalarial activity of metal complexes of cross-bridged tetraazamacrocyclic ligands

    OpenAIRE

    Timothy J. Hubin; Amoyaw, Prince N. -A.; Roewe, Kimberly D.; Simpson, Natalie C.; Maples, Randall D.; Carder Freeman, TaRynn N.; Amy N. Cain; Le, Justin G.; Stephen J Archibald; Khan, Shabana I.; Tekwani, Babu L.; Khan, M. O. Faruk

    2014-01-01

    Using transition metals such as manganese(II), iron(II), cobalt(II), nickel(II), copper(II), and zinc(II), several new metal complexes of cross-bridged tetraazamacrocyclic chelators namely, cyclen- and cyclam-analogs with benzyl groups, were synthesized and screened for in vitro antimalarial activity against chloroquine-resistant (W2) and chloroquine-sensitive (D6) strains of Plasmodium falciparum. The metal-free chelators tested showed little or no antimalarial activity. All the metal comple...

  4. Evaluation of the effect of pyrimethamine, an anti-malarial drug, on HIV-1 replication

    OpenAIRE

    Oguariri, Raphael M.; Joseph W Adelsberger; Michael W Baseler; Imamichi, Tomozumi

    2010-01-01

    Co-infection of human immunodeficiency virus (HIV) with malaria is one of the pandemic problems in Africa and parts of Asia. Here we investigated the impact of PYR and two other clinical anti-malarial drugs (chloroquine [CQ] or artemisinin [ART]) on HIV-1 replication. Peripheral blood mononuclear cells (PBMCs) or MT-2 cells were infected with HIVNL4.3 strain and treated with different concentrations of the anti-malarial drugs. HIV-1 replication was measured using p24 ELISA. We show that 10 μM...

  5. Access to artesunate-amodiaquine, quinine and other anti-malarials: policy and markets in Burundi

    Directory of Open Access Journals (Sweden)

    Dismas Baza

    2011-02-01

    Full Text Available Abstract Background Malaria is the leading cause of morbidity and mortality in post-conflict Burundi. To counter the increasing challenge of anti-malarial drug resistance and improve highly effective treatment Burundi adopted artesunate-amodiaquine (AS-AQ as first-line treatment for uncomplicated Plasmodium falciparum malaria and oral quinine as second-line treatment in its national treatment policy in 2003. Uptake of this policy in the public, private and non-governmental (NGO retail market sectors of Burundi is relatively unknown. This study was conducted to evaluate access to national policy recommended anti-malarials. Methods Adapting a standardized methodology developed by Health Action International/World Health Organization (HAI/WHO, a cross-sectional survey of 70 (24 public, 36 private, and 10 NGO medicine outlets was conducted in three regions of Burundi, representing different levels of transmission of malaria. The availability on day of the survey, the median prices, and affordability (in terms of number of days' wages to purchase treatment of AS-AQ, quinine and other anti-malarials were calculated. Results Anti-malarials were stocked in all outlets surveyed. AS-AQ was available in 87.5%, 33.3%, and 90% of public, private, and NGO retail outlets, respectively. Quinine was the most common anti-malarial found in all outlet types. Non-policy recommended anti-malarials were mainly found in the private outlets (38.9% compared to public (4.2% and NGO (0% outlets. The median price of a course of AS-AQ was US$0.16 (200 Burundi Francs, FBu for the public and NGO markets, and 3.5-fold higher in the private sector (US$0.56 or 700 FBu. Quinine tablets were similarly priced in the public (US$1.53 or 1,892.50 FBu, private and NGO sectors (both US$1.61 or 2,000 FBu. Non-policy anti-malarials were priced 50-fold higher than the price of AS-AQ in the public sector. A course of AS-AQ was affordable at 0.4 of a day's wage in the public and NGO sectors

  6. Retinal toxicity induced by antimalarial drugs: literature review and case report.

    Science.gov (United States)

    Garza-Leon, Manuel; Flores-Alvarado, Diana Elsa; Muñoz-Bravo, Juan Manuel

    2016-01-01

    Antimalarial drugs are widely used in several countries for control of rheumatologic diseases such as systemic lupus erythematosus and rheumatoid arthritis. They are still used in Mexico because of their low cost and few secondary effects, most of which are mild and reversible. Even so, at an ophthalmological level, they could produce irreversible visual damage, which is why it is important to have ophthalmological evaluation and proper follow up. We present a clinical case as an example of characteristic ophthalmological findings as well as risk factors for retinal toxicity. We then discuss guidelines for diagnosis and follow up of patients who use antimalarial drugs for the treatment of rheumatologic illnesses. PMID:27391903

  7. Synthesis and structure-activity relationships of potent antitumor active quinoline and naphthyridine derivatives.

    Science.gov (United States)

    Srivastava, Sanjay K; Jha, Amrita; Agarwal, Shiv K; Mukherjee, Rama; Burman, Anand C

    2007-11-01

    The disease of cancer has been ranked second after cardiovascular diseases and plant-derived molecules have played an important role for the treatment of cancer. Nine cytotoxic plant-derived molecules such as vinblastine, vincristine, navelbine, etoposide, teniposide, taxol, taxotere, topotecan and irinotecan have been approved as anticancer drugs. Recently, epothilones are being emerging as future potential anti-tumor agents. However, targeted cancer therapy has now been rapidly expanding and small organic molecules are being exploited for this purpose. Amongst target specific small organic molecules, quinazoline was found as one of the most successful chemical class in cancer chemotherapy as three drugs namely Gefitinib, Erlotinib and Canertinib belong to this series. Now, quinazoline related chemical classes such as quinolines and naphthyridines are being exploited in cancer chemotherapy and a number of molecules such as compounds EKB-569 (52), HKI-272 (78) and SNS-595 (127a) are in different phases of clinical trials. This review presents the synthesis of quinolines and naphthyridines derivatives, screened for anticancer activity since year 2000. The synthesis of most potent derivatives in each prototype has been delineated. A brief structure activity relationship for each prototype has also been discussed. It has been observed that aniline group at C-4, aminoacrylamide substituents at C-6, cyano group at C-3 and alkoxy groups at C-7 in the quinoline ring play an important role for optimal activity. While aminopyrrolidine functionality at C-7, 2'-thiazolyl at N-1 and carboxy group at C-3 in 1,8-naphthyridine ring are essential for eliciting the cytotoxicity. This review would help the medicinal chemist to design and synthesize molecules for targeted cancer chemotherapy. PMID:18045063

  8. Cucurbit[n]urils-induced room temperature phosphorescence of quinoline derivatives

    International Nuclear Information System (INIS)

    The cucurbit[7,8]urils (Q[7] and Q[8])-induced room temperature phosphorescence (RTP) of quinoline and its derivatives were firstly found in the cucurbit[n]urils chemistry. The luminophores (quinolines) and their RTP are affected by the concentration of different Q[n]s, heavy metal ions and amounts, and pH. The RTP lifetime of the luminophore has been investigated. In presence of Na2SO3, the cation Tl+ led to stronger Q[n]-induced RTP, while the RTP lifetimes of luminophore/Q[7 or 8]/KI were generally longer than that of luminophore/Q[7 or 8]/TlNO3, the RTP lifetimes of these systems were between 0.18 and 47.4 ms. Contrary to the stable 1:2 Q[8]:guest ternary inclusion complexes at lower pHs, as suggested by 1H NMR, electronic absorption and fluorescence spectroscopy, low Q[8]-induced room temperature phosphorescence was observed. However, at higher pHs, high intensity of cucurbit[n]urils-induced room temperature phosphorescence of these quinoline derivatives were observed, and a 1:1 Q[8]:guest inclusion complex was formed. Investigations of dependence of RTP intensity on concentration of Q[n] revealed that the highest intensity of the Q[n]-induced RTP was observed at a low mole ratio of host:guest, which is closed to 1:1. It was presumably resulted from the strong interaction of Q[n] and these guests due to the combined hydrophobic cavity interaction and the hydrophilic portal interaction of the cucurbit[n]urils with the nitrogen heterocycles guest

  9. Synthesis of C-glycosyl triazolyl quinoline-based fluorescent sensors for the detection of mercury ions.

    Science.gov (United States)

    Wang, Linfang; Jin, Jianzhong; Zhao, Linwei; Shen, Hongyun; Shen, Chao; Zhang, Pengfei

    2016-10-01

    A series of novel C-glycosyl triazolyl quinoline-based fluorescent sensors have been synthesized via click chemistry. It was found that novel sensors exhibited good selectivity for Hg(2+) over many other metal ions. The glucose framework was introduced to increase the water-solubility of the fluorescent sensors and broaden its application for the detection of Hg(II) in the water-solubility biological systems. The mechanism of the chemodosimetric behavior of the sensors has been attributed to a binding mode of triazolyl quinoline with Hg(2+) which has been characterized by a number of spectroscopic techniques.

  10. Thermo-optical properties of 1H[3,4-b] quinoline films used in electroluminescent devices

    Science.gov (United States)

    Jaglarz, Janusz; Kępińska, Mirosława; Sanetra, Jerzy

    2014-06-01

    Electroluminescence cells with H[3,4-b] quinoline layers are promising devices for a blue light emitting EL diode. This work measured the optical reflectance as a function of temperature in copolymers PAQ layers deposited on Si crystalline substrate. Using the extended Cauchy dispersion model of the film refractive index we determined the thermo-optical coefficients for quinoline layers in the temperature range of 76-333 K from combined ellipsometric and spectrofotometric studies. The obtained values of thermo-optical coefficients of thin PAQ film, were negative and ranged in 5-10 × 10-4 [1/K].

  11. Determination of three physical properties of quinoline ionic liquids with hexafluorophosphate

    OpenAIRE

    Tang Dan; Wang Litao; Yao Shun; Chen Yanwen; Wang Daocai; Song Hang

    2016-01-01

    Densities of one acidic ionic liquid (IL) Quinolinum hexafluorophosphate ([HBpy][PF6]), and four neutral dicationic ionic liquids (ILs) based on quinoline and hexafluoro-phosphate and linked with poly(ethylene glycol) (PEG): ([PEG200-DIL][PF6]2, [PEG400-DIL][PF6]2, [PEG800-DIL][PF6]2 and [PEG1000-DIL][PF6]2) were determined. In addition, the solubilities of six ILs in six lower alcohols, water, acetonitrile and diethyl ether were measured at 288.15 K; and the hydroscopicity of above five ILs ...

  12. Ring-substituted 4-Hydroxy-1H-quinolin-2-ones: Preparation and Biological Activity

    Directory of Open Access Journals (Sweden)

    Jiri Dohnal

    2009-03-01

    Full Text Available In the study, a series of twelve ring-substituted 4-hydroxy-1H-quinolin-2-one derivatives were prepared. The procedures for synthesis of the compounds are presented. The compounds were analyzed using RP-HPLC to determine lipophilicity and tested for their photosynthesis-inhibiting activity using spinach (Spinacia oleracea L. chloroplasts. All the synthesized compounds were also evaluated for antifungal activity using in vitro screening with eight fungal strains. For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed, as well as their structure-activity relationships (SAR.

  13. Metabolic pathways of quinoline, indole and their methylated analogs by Desulfobacterium indolicum (DSM 3383)

    DEFF Research Database (Denmark)

    Johansen, S.S.; Licht, D.; Arvin, E.;

    1997-01-01

    The transformation of quinoline, isoquinoline and 3-, 4-, 6- and 8-methylquinoline by Desulfobacterium indolicum was compared with that of the N-containing analogues indole and 1-, 2-, 3- and 7-methylindole. The metabolites were identified using high-performance liquid chromatography with UV......-methyloxindole and 3- and 4-methyl-2-quinolinone, was observed within 162 days of incubation. These degradation products accumulated in stoichiometric amounts, while 6- and 8-methyl-2-quinolinone were further degraded to 6- and 8-methyl-3,4-dihydro-2-quinolinone in stoichiometric amounts. Isoquinoline, 2...

  14. Synthesis of (iso)quinoline, (iso)coumarin and (iso)chromene derivatives from acetylene compounds

    Science.gov (United States)

    Ryabukhin, D. S.; Vasilyev, A. V.

    2016-06-01

    Published data on the methods of synthesis of quinoline, isoquinoline, coumarin, isocoumarin, chromene and isochromene derivatives from acetylene compounds are summarized. The reactions catalyzed by metal complexes (Pd, Pt, Ru, Rh, Au, Ag, Ni, Cu, etc.) and transformations induced by various electrophilic reagents (Brynsted and Lewis acids) are considered. Moieties of the mentioned heterocyclic systems are present in many biologically active natural products and pharmaceutical agents. Besides, derivatives of these heterocycles are used in the manufacture of catalysts, dyes, perfumery and cosmetic products, corrosion inhibitors and so on. The bibliography includes 211 references.

  15. Synthesis of new biphenyl-substituted quinoline derivatives, preliminary screening and docking studies

    Indian Academy of Sciences (India)

    Nellisara D Shashikumar; Ganganaika Krishnamurthy; Halehatti S Bhojyanaik; Mayasandra R Lokesh; Kaginalli S Jithendrakumara

    2014-01-01

    New quinoline derivatives containing biphenyl ring were synthesized and characterized by IR, 1H NMR and mass spectral studies. The synthesized compounds were screened for antimicrobial, anthelmintic activities as well as free radical scavenging property against the DPPH radical. The minimum inhibition concentration values showed promising inhibiting activity and are potent biological agents. The compounds showed minimum binding energy towards -tubulin. The compounds 11a, 11c, 13c and 13d have good affinity towards the active pocket and may be considered as a good inhibitor of -tubulin.

  16. 2-Oxo-4-phenyl-1,2,5,6-tetrahydrobenzo[h]quinoline-3-carbonitrile

    Directory of Open Access Journals (Sweden)

    Abdullah M. Asiri

    2011-09-01

    Full Text Available In the molecule of the title compound, C20H14N2O, the tetrahydrobenzo[h]quinoline fused-ring system is buckled owing to the ethylene –CH2CH2– fragment, the benzene ring and the pyridine ring being twisted by 19.7 (1°. The 4-substituted aromatic ring is bent away from the pyridine ring by 62.9 (1° in order to avoid crowding the cyanide substituent. In the crystal, two molecules are linked by a pair of N—H...O hydrogen bonds to form a centrosymmetric dimer.

  17. Biogeochemical Cycle of Methanol in Anoxic Deep-Sea Sediments

    Science.gov (United States)

    Yanagawa, Katsunori; Tani, Atsushi; Yamamoto, Naoya; Hachikubo, Akihiro; Kano, Akihiro; Matsumoto, Ryo; Suzuki, Yohey

    2016-01-01

    The biological flux and lifetime of methanol in anoxic marine sediments are largely unknown. We herein reported, for the first time, quantitative methanol removal rates in subsurface sediments. Anaerobic incubation experiments with radiotracers showed high rates of microbial methanol consumption. Notably, methanol oxidation to CO2 surpassed methanol assimilation and methanogenesis from CO2/H2 and methanol. Nevertheless, a significant decrease in methanol was not observed after the incubation, and this was attributed to the microbial production of methanol in parallel with its consumption. These results suggest that microbial reactions play an important role in the sources and sinks of methanol in subseafloor sediments. PMID:27301420

  18. Prioritization of anti-malarial hits from nature: chemo-informatic profiling of natural products with in vitro antiplasmodial activities and currently registered anti-malarial drugs

    OpenAIRE

    Egieyeh, Samuel Ayodele; Syce, James; Malan, Sarel F.; Christoffels, Alan

    2016-01-01

    Background A large number of natural products have shown in vitro antiplasmodial activities. Early identification and prioritization of these natural products with potential for novel mechanism of action, desirable pharmacokinetics and likelihood for development into drugs is advantageous. Chemo-informatic profiling of these natural products were conducted and compared to currently registered anti-malarial drugs (CRAD). Methods Natural products with in vitro antiplasmodial activities (NAA) we...

  19. Mind the gaps - the epidemiology of poor-quality anti-malarials in the malarious world - analysis of the WorldWide Antimalarial Resistance Network database

    OpenAIRE

    Tabernero, Patricia; Facundo M Fernández; Green, Michael; Guerin, Philippe J; Newton, Paul N.

    2014-01-01

    Background Poor quality medicines threaten the lives of millions of patients and are alarmingly common in many parts of the world. Nevertheless, the global extent of the problem remains unknown. Accurate estimates of the epidemiology of poor quality medicines are sparse and are influenced by sampling methodology and diverse chemical analysis techniques. In order to understand the existing data, the Antimalarial Quality Scientific Group at WWARN built a comprehensive, open-access, global datab...

  20. Hainan Methanol Project Kicks off

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    @@ The State Development and Reform Commission has recently approved the feasibility study report on the 600,000-ton methanol unit project, which is a joint venture between CNOOC Chemicals Ltd and Hong Kong Jiantao Chemical Group. Negotiations and design of the auxiliary facilities will start soon. The project will use natural gas from the second phase of Dongfang Gas Field in South China Sea as raw material. The main units of the project will be procured through international bidding so as to select the world's latest patent technology and production process. Construction is scheduled to kick off before the end of this year. The project is expected to come into operation in the first half of this year.

  1. Recycling of greenhouse gases via methanol

    Energy Technology Data Exchange (ETDEWEB)

    Bill, A. [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Eliasson, B.; Kogelschatz, U. [ABB Corporate Research Center, Baden-Daettwil (Switzerland)

    1997-06-01

    Greenhouse gas emissions to the atmosphere can be mitigated by using direct control technologies (capture, disposal or chemical recycling). We report on carbon dioxide and methane recycling with other chemicals, especially with hydrogen and oxygen, to methanol. Methanol synthesis from CO{sub 2} is investigated on various catalysts at moderate pressures ({<=}30 bar) and temperatures ({<=}300{sup o}C). The catalysts show good methanol activities and selectivities. The conversion of CO{sub 2} and CH{sub 4} to methanol is also studied in a silent electrical discharge at pressures of 1 to 4 bar and temperatures close to room temperature. Methanol yields are given for mixtures of CO{sub 2}/H{sub 2}, CH{sub 4}/O{sub 2} and also for CH{sub 4} and air mixtures. (author) 2 figs., 5 refs.

  2. In vivo antimalarial activities of russelia equisetiformis in plasmodium berghei infected mice

    Directory of Open Access Journals (Sweden)

    O Ojurongbe

    2015-01-01

    Full Text Available The rising problem of resistance to most commonly used antimalarials remains a major challenge in the control of malaria suggesting the need for new antimalarial agents. This work explores the antiplasmodial potential of ethanol extract of Russelia equisetiformis in chloroquine Plasmodium berghei infected mice. Swiss albino mice were intraperitoneally infected with chloroquine-resistant P. berghei (ANKA. Experimental mice were treated for four days consecutively with graded doses of plant extracts and standard antimalarial drugs (artesunate and chloroquine at a dose of 10 mg/kg body weight used as control. The extract showed a dose-dependent activity in the chemosuppression of P. berghei parasites by 31.6, 44.7, 48.4 and 86.5% at doses of 100, 200, 400 and 800 mg/kg, while chloroquine (10 mg/kg and artesunate produced 59.4 and 68.4%, respectively. The extract showed a significant decrease in parasitaemia (P<0.05. The level of parasitemia and decrease in weight in all the treated groups was significantly lower (P<0.05 compared with the infected but untreated mice. The plant extract was devoid of toxicity at the highest dose tested (5000 mg/kg. The study concluded that the ethanol extract of R. equisetiformis possesses antimalarial effect, which supports the folk medicine claim of its use in the treatment of malaria.

  3. Deployment of ACT antimalarials for treatment of malaria: challenges and opportunities

    Directory of Open Access Journals (Sweden)

    Leslie Toby

    2008-12-01

    Full Text Available Abstract Following a long period when the effectiveness of existing mono-therapies for antimalarials was steadily declining with no clear alternative, most malaria-endemic countries in Africa and Asia have adopted artemisinin combination therapy (ACT as antimalarial drug policy. Several ACT drugs exist and others are in the pipeline. If properly targeted, they have the potential to reduce mortality from malaria substantially. The major challenge now is to get the drugs to the right people. Current evidence suggests that most of those who need the drugs do not get them. Simultaneously, a high proportion of those who are given antimalarials do not in fact have malaria. Financial and other barriers mean that, in many settings, the majority of those with malaria, particularly the poorest, do not access formal healthcare, so the provision of free antimalarials via this route has only limited impact. The higher cost of ACT creates a market for fake drugs. Addressing these problems is now a priority. This review outlines current evidence, possible solutions and research priorities.

  4. Tritium labelling and characterization of the antimalarial drug (+/-)-chloroquine by several methods

    Energy Technology Data Exchange (ETDEWEB)

    Egan, J.A.Judith A.; Laseter, Anne G.; Filer, C.N.Crist N. E-mail: crist.filer@perkinelmer.com

    2002-09-01

    To study its mechanism of antimalarial action, a tritium labelled analogue of (+/-)-chloroquine was required at high specific activity. Two synthetic methods were successfully employed. [3-{sup 3}H] (+/-)-Chloroquine 2 was prepared by the catalytic tritium dehalogenation of an iodo precursor and [N-ethyl-{sup 3}H] (+/-)-chloroquine 4 was synthesized by the alkylation of (+/-)-desethylchloroquine with [{sup 3}H] ethyl iodide.

  5. A novel multiple-stage antimalarial agent that inhibits protein synthesis

    NARCIS (Netherlands)

    Baragana, B.; Hallyburton, I.; Lee, M.C.; Norcross, N.R.; Grimaldi, R.; Otto, T.D.; Proto, W.R.; Blagborough, A.M.; Meister, S.; Wirjanata, G.; Ruecker, A.; Upton, L.M.; Abraham, T.S.; Almeida, M.J.; Pradhan, A.; Porzelle, A.; Martinez, M.S.; Bolscher, J.M.; Woodland, A.; Norval, S.; Zuccotto, F.; Thomas, J.; Simeons, F.; Stojanovski, L.; Osuna-Cabello, M.; Brock, P.M.; Churcher, T.S.; Sala, K.A.; Zakutansky, S.E.; Jimenez-Diaz, M.B.; Sanz, L.M.; Riley, J.; Basak, R.; Campbell, M.; Avery, V.M.; Sauerwein, R.W.; Dechering, K.J.; Noviyanti, R.; Campo, B.; Frearson, J.A.; Angulo-Barturen, I.; Ferrer-Bazaga, S.; Gamo, F.J.; Wyatt, P.G.; Leroy, D.; Siegl, P.; Delves, M.J.; Kyle, D.E.; Wittlin, S.; Marfurt, J.; Price, R.N.; Sinden, R.E.; Winzeler, E.A.; Charman, S.A.; Bebrevska, L.; Gray, D.W.; Campbell, S.; Fairlamb, A.H.; Willis, P.A.; Rayner, J.C.; Fidock, D.A.; Read, K.D.; Gilbert, I.H.

    2015-01-01

    There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. Here we describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activ

  6. Oxidative pentose phosphate pathway inhibition is a key determinant of antimalarial induced cancer cell death.

    Science.gov (United States)

    Salas, E; Roy, S; Marsh, T; Rubin, B; Debnath, J

    2016-06-01

    Despite immense interest in using antimalarials as autophagy inhibitors to treat cancer, it remains unclear whether these agents act predominantly via autophagy inhibition or whether other pathways direct their anti-cancer properties. By comparing the treatment effects of the antimalarials chloroquine (CQ) and quinacrine (Q) on KRAS mutant lung cancer cells, we demonstrate that inhibition of the oxidative arm of the pentose phosphate pathway (oxPPP) is required for antimalarial induced apoptosis. Despite inhibiting autophagy, neither CQ treatment nor RNAi against autophagy regulators (ATGs) promote cell death. In contrast, Q triggers high levels of apoptosis, both in vitro and in vivo, and this phenotype requires both autophagy inhibition and p53-dependent inhibition of the oxPPP. Simultaneous genetic targeting of the oxPPP and autophagy is sufficient to trigger apoptosis in lung cancer cells, including cells lacking p53. Thus, in addition to reduced autophagy, oxPPP inhibition serves as an important determinant of antimalarial cytotoxicity in cancer cells.

  7. Antimalarial qinghaosu/artemisinin:The therapy worthy of a Nobel Prize

    Institute of Scientific and Technical Information of China (English)

    Jerapan Krungkrai

    2016-01-01

    Malaria is a major cause of human morbidity and mortality in the tropical endemic countries worldwide. This is largely due to the emergence and spread of resistance to most antimalarial drugs currently available. Based on the World Health Organization recommendation, artemisinin-based combination therapies are now used as first-line treatment for Plasmodium falciparum malaria. Artemisinin or qinghaosu (Chinese name) and its derivatives are highly potent, rapidly acting antimalarial drugs. Artemisinin was discovered in 1971 by a Chinese medical scientist Youyou Tu, who was awarded the Nobel Prize in 2015 on her discovering the antimalarial properties of qinghaosu from the traditional Chinese qinghao plant. Nevertheless, artemisinin resistance in falciparum malaria patients has first emerged on the Thai-Cambodian border in 2009, which is now prevalent across mainland Southeast Asia from Vietnam to Myanmar. Here, we reviewed malaria disease severity, history of artemisinin discovery, chemical structure, mechanism of drug action, artemisinin-based combination therapies, emergence and spread of drug resistance, including the recent findings on mechanism of resistance in the falciparum malaria parasite. This poses a serious threat to global malaria control and prompts renewed efforts for the urgent development of new antimalarial drugs.

  8. Detecting the antimalarial artemisinin in plant extracts using near-infrared spectroscopy

    Science.gov (United States)

    The antimalarial artemisinin is produced by Artemisia annua L and can be used to kill the protozoan parasite Plasmodium, which is spread by mosquitoes. Artemisinin is extracted from these plants through tea preparation. The artemisinin content of the tea varies depending on how much artemisinin was ...

  9. Fixed dose combination of arterolane and piperaquine: a newer prospect in antimalarial therapy.

    Science.gov (United States)

    Patil, Cy; Katare, Ss; Baig, Ms; Doifode, Sm

    2014-07-01

    Malaria has been very prevalent vector-borne disease in India and until date bears enormous implications on health care services of the country. Over the period of time, the development of resistance to traditional antimalarials like chloroquine has been posed as major deterrent in efforts of malaria control. As the drug resistance is today universally prevalent, especially in Plasmodium falciparum species, major burden of malarial control resides with the new artemisinin drug class. However, arterolane is one of the first fully synthetic non-artemisinin antimalarial compound with rapid schizontocidal activity, hence offering an alternative to artemisinin drugs in malaria control. Piperaquine is a synthetic bisquinoline (4-amioquinoline Antimalarial) with slow and longer schizontocidal activity. Therefore their combination has been shown to provide rapid parasitemic clearance and quick relief of most malaria-related symptoms along with prevention of recrudescences. This combination was approved by Drugs Controller General of India in 2011 for treatment of uncomplicated P. falciparum malaria. The article is aimed at to review this newer prospect in antimalarial therapy for which comprehensive database search was done in Google, Google Scholar, PubMed using the terms "Malaria," "Arterolane," "OZ277," "Piperaquine," and "Artemisinin combination therapy." A total of 323 articles were screened and 28 articles were considered for this review along with the World Health Organization and National malarial program guidelines.

  10. Probing the antimalarial mechanism of artemisinin and OZ277 (arterolane) with nonperoxidic isosteres and nitroxyl radicals.

    Science.gov (United States)

    Fügi, Matthias A; Wittlin, Sergio; Dong, Yuxiang; Vennerstrom, Jonathan L

    2010-03-01

    Peroxidic antimalarials such as the semisynthetic artemisinins are critically important in the treatment of drug-resistant malaria. Nevertheless, their peroxide bond-dependent mode of action is still not well understood. Using combination experiments with cultured Plasmodium falciparum cells, we investigated the interactions of the nitroxide radical spin trap, 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), and four of its analogs with artemisinin and the ozonide drug development candidate OZ277. The antagonism observed for combinations of artemisinin or OZ277 with the TEMPO analogs supports the hypothesis that the formation of carbon-centered radicals is critical for the activity of these two antimalarial peroxides. The TEMPO analogs showed a trend toward greater antagonism with artemisinin than they did with OZ277, an observation that can be explained by the greater tendency of artemisinin-derived carbon-centered radicals to undergo internal self-quenching reactions, resulting in a lower proportion of radicals available for subsequent chemical reactions such as the alkylation of heme and parasite proteins. In a further mechanistic experiment, we tested both artemisinin and OZ277 in combination with their nonperoxidic analogs. The latter had no effect on the antimalarial activities of the former. These data indicate that the antimalarial properties of peroxides do not derive from reversible interactions with parasite targets. PMID:20028825

  11. Antimalarial qinghaosu/artemisinin: The therapy worthy of a Nobel Prize

    Directory of Open Access Journals (Sweden)

    Jerapan Krungkrai

    2016-05-01

    Full Text Available Malaria is a major cause of human morbidity and mortality in the tropical endemic countries worldwide. This is largely due to the emergence and spread of resistance to most antimalarial drugs currently available. Based on the World Health Organization recommendation, artemisinin-based combination therapies are now used as first-line treatment for Plasmodium falciparum malaria. Artemisinin or qinghaosu (Chinese name and its derivatives are highly potent, rapidly acting antimalarial drugs. Artemisinin was discovered in 1971 by a Chinese medical scientist Youyou Tu, who was awarded the Nobel Prize in 2015 on her discovering the antimalarial properties of qinghaosu from the traditional Chinese qinghao plant. Nevertheless, artemisinin resistance in falciparum malaria patients has first emerged on the Thai-Cambodian border in 2009, which is now prevalent across mainland Southeast Asia from Vietnam to Myanmar. Here, we reviewed malaria disease severity, history of artemisinin discovery, chemical structure, mechanism of drug action, artemisinin-based combination therapies, emergence and spread of drug resistance, including the recent findings on mechanism of resistance in the falciparum malaria parasite. This poses a serious threat to global malaria control and prompts renewed efforts for the urgent development of new antimalarial drugs.

  12. Atovaquone and quinine anti-malarials inhibit ATP binding cassette transporter activity

    OpenAIRE

    Rijpma, S.R.; Heuvel, J. J.; van de Velden, M.; Sauerwein, R. W.; Russel, F. G.; Koenderink, J.B.

    2014-01-01

    BACKGROUND: Therapeutic blood plasma concentrations of anti-malarial drugs are essential for successful treatment. Pharmacokinetics of pharmaceutical compounds are dependent of adsorption, distribution, metabolism, and excretion. ATP binding cassette (ABC) transport proteins are particularly involved in drug deposition, as they are located at membranes of many uptake and excretory organs and at protective barriers, where they export endogenous and xenobiotic compounds, including pharmaceutica...

  13. A SAR and QSAR Study of New Artemisinin Compounds with Antimalarial Activity

    Directory of Open Access Journals (Sweden)

    Cleydson Breno R. Santos

    2013-12-01

    Full Text Available The Hartree-Fock method and the 6-31G** basis set were employed to calculate the molecular properties of artemisinin and 20 derivatives with antimalarial activity. Maps of molecular electrostatic potential (MEPs and molecular docking were used to investigate the interaction between ligands and the receptor (heme. Principal component analysis and hierarchical cluster analysis were employed to select the most important descriptors related to activity. The correlation between biological activity and molecular properties was obtained using the partial least squares and principal component regression methods. The regression PLS and PCR models built in this study were also used to predict the antimalarial activity of 30 new artemisinin compounds with unknown activity. The models obtained showed not only statistical significance but also predictive ability. The significant molecular descriptors related to the compounds with antimalarial activity were the hydration energy (HE, the charge on the O11 oxygen atom (QO11, the torsion angle O1-O2-Fe-N2 (D2 and the maximum rate of R/Sanderson Electronegativity (RTe+. These variables led to a physical and structural explanation of the molecular properties that should be selected for when designing new ligands to be used as antimalarial agents.

  14. An environmentally benign one pot synthesis of substituted quinolines catalysed by fluoroboric acid based ionic liquid

    Indian Academy of Sciences (India)

    A Rajendran; C Karthikeyan; K Rajathi; D Ragupathy

    2012-07-01

    Organic synthesis generally required large amount of solvent, avoiding the use of organic solvents in synthesis is a paradigm shift directed at developing more benign chemistry, and with ionic liquids surprisingly can lead to access to new compounds. An elegant one-pot synthesis of quinoline derivatives has been achieved by reaction of substituted anilines with -ketoester at 60°C in ethanol using an ionic liquid [Et3NH]+[BF4]−as catalyst. All the reactions gave products with high degree of purity and excellent yield (78-93%) within the shorter span of time (20-65 min) than those reactions with conventional methods. The screening of solvents as well as the reuse of ionic liquid has been evaluated. The structure of the products has been elucidated by spectral and analytical data. The present scope and potential economic impact of the reaction are demonstrated by the synthesis of substituted quinolines. Remaining challenges and future perspectives of the new transformation are discussed.

  15. Rotational spectra of quinoline and of isoquinoline: spectroscopic constants and electric dipole moments

    Science.gov (United States)

    Kisiel, Z.; Desyatnyk, O.; Pszczółkowski, L.; Charnley, S. B.; Ehrenfreund, P.

    2003-01-01

    Rotational spectra of quinoline and of isoquinoline have been observed in the centimeter- and millimeter-wave regions. The spectra were assigned on the basis of bands formed by high- J transitions, which were measured up to J″⩽128 and ν⩽234 GHz. Complementary measurements were also made on low- J, centimeter-wave spectra observed in supersonic expansion and with fully resolved nuclear quadrupole hyperfine structure. Accurate rotational, centrifugal distortion and hyperfine splitting constants for the ground states of both molecules are reported. The electric dipole moments for the two molecules were also determined from Stark effect measurements and are μa=0.14355(19), μb=2.0146(17), μtot=2.0197(17) D for quinoline, and μa=2.3602(21), μb=0.9051(14), μtot=2.5278(20) D for isoquinoline. The experimental observables were found to be rather accurately predicted by MP2/6-31G** ab initio calculations, and corresponding molecular geometries are also reported.

  16. Synthesis, characterization and emission properties of quinolin-8-olato chelated ruthenium organometallics

    Indian Academy of Sciences (India)

    Bikash Kumar Panda

    2004-08-01

    The reaction of Ru(RL1)(PPh3)2(CO)Cl, 1, with quinolin-8-ol (HQ) has afforded complexes of the type [Ru(RL2)(PPh3)2(CO)(Q)], 3, in excellent yield (RL1 is C6H2O-2-CHNHC6H4R()-3-Me-5, RL2 is C6H2OH-2-CHNC6H4R()-3-Me-5 and R is Me, OMe, Cl). In this process, quinolin-8-olato (Q) undergoes five-membered chelation, the iminium-phenolato function tautomerizing to the imine-phenol function. In dichloromethane solution, 3 displays a quasireversible 3+/3 couple near 0×50 V vs SCE (3+ is the ruthenium (III) analogue of 3). Coulometrically generated solutions of 3+ display a strong absorption near 395 nm associated with a shoulder near 475 nm and rhombic EPR spectra with values near 2.55, 2.13, 1.89. Solutions of 3 absorb near 415 nm and emit near 510 nm at 298 K and 585 nm at 77 K. The fluorescence is believed to originate from the 3MLCT state.

  17. Application of Porous Nickel-Coated TiO2 for the Photocatalytic Degradation of Aqueous Quinoline in an Internal Airlift Loop Reactor

    Directory of Open Access Journals (Sweden)

    Mingxin Huo

    2012-02-01

    Full Text Available P25 film, prepared by a facile dip-coating method without any binder, was further developed in a recirculating reactor for quinoline removal from synthetic wastewater. Macroporous foam Ni, which has an open three-dimensional network structure, was utilized as a substrate to make good use of UV rays. Field emission scanning electron microscopy and X-ray diffraction analysis showed that the coated/calcinated P25 films consisted of two crystal phases, and had a number of uniform microcracks on the surface. The effects of initial quinoline concentration, light intensity, reaction temperature, aeration, and initial pH were studied. Increased reaction time, light intensity, environmental temperature, and gas aeration were found to significantly improve the quinoline removal efficiency. The aeration effect of oxygen dependency on the quinoline degradation had the trend pure oxygen > air > no gas > pure nitrogen with free O2. The solution pH crucially affected quinoline photodegradation; the high electrostatic adsorption of quinoline molecules on the TiO2 surface was strongly pH dependent. 2-Pyridine-carboxaldehyde, 3-pyridinecarboxaldehyde, and 2(1H-quinolinone were identified as the major intermediates of quinoline degradation. Based on these intermediates, a primary degradation mechanism was proposed. This reusable P25 film benefits the photodegradation of water contaminants and has potential in other various applications.

  18. Compound antimalarial ethosomal cataplasm: preparation, evaluation, and mechanism of penetration enhancement

    Directory of Open Access Journals (Sweden)

    Shen S

    2015-06-01

    Full Text Available Shuo Shen, Shu-Zhi Liu, Yu-Shi Zhang, Mao-Bo Du, Ai-Hua Liang, Li-Hua Song, Zu-Guang Ye Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China Abstract: Malaria is still a serious public health problem in some parts of the world. The problems of recurrence and drug resistance are increasingly more serious. Thus, it is necessary to develop a novel antimalarial agent. The objectives of this study were to construct a novel compound antimalarial transdermal nanosystem–ethosomal cataplasm, to investigate its characteristics and efficiency, and to systematically explore the penetration-enhancing mechanisms of ethosomal cataplasm. Artesunate-loaded ethosomes and febrifugine-loaded ethosomes were prepared, and their characteristics were evaluated. Drug-loaded ethosomes were incorporated in the matrix of cataplasm to form the compound antimalarial ethosomal cataplasm. With the help of ethosomal technology, the accumulated permeation quantity of artesunate significantly increased at 8 hours after administration, which was 1.57 times as much as that of conventional cataplasm. Soon after administration, the ethosomal cataplasm could make a large quantity of antimalarial drug quickly penetrate through skin, then the remaining drug in the ethosomal cataplasm could be steadily released. These characteristics of ethosomal cataplasm are favorable for antimalarial drugs to kill Plasmodium spp. quickly and prevent the resurgence of Plasmodium spp. As expected, the ethosomal cataplasm showed good antimalarial efficiency in this experiment. The negative conversion rates were 100% and the recurrence rates were 0% at all dosages. The mechanism of penetration enhancement of the ethosomal cataplasm was systematically explored using an optics microscope, polarization microscope, and transmission electron microscopy. The microstructure, ultrastructure, and birefringent structure in skin were observed. Data

  19. Hyperparasitaemia and low dosing are an important source of anti-malarial drug resistance

    Directory of Open Access Journals (Sweden)

    Lee Sue J

    2009-11-01

    Full Text Available Abstract Background Preventing the emergence of anti-malarial drug resistance is critical for the success of current malaria elimination efforts. Prevention strategies have focused predominantly on qualitative factors, such as choice of drugs, use of combinations and deployment of multiple first-line treatments. The importance of anti-malarial treatment dosing has been underappreciated. Treatment recommendations are often for the lowest doses that produce "satisfactory" results. Methods The probability of de-novo resistant malaria parasites surviving and transmitting depends on the relationship between their degree of resistance and the blood concentration profiles of the anti-malarial drug to which they are exposed. The conditions required for the in-vivo selection of de-novo emergent resistant malaria parasites were examined and relative probabilities assessed. Results Recrudescence is essential for the transmission of de-novo resistance. For rapidly eliminated anti-malarials high-grade resistance can arise from a single drug exposure, but low-grade resistance can arise only from repeated inadequate treatments. Resistance to artemisinins is, therefore, unlikely to emerge with single drug exposures. Hyperparasitaemic patients are an important source of de-novo anti-malarial drug resistance. Their parasite populations are larger, their control of the infection insufficient, and their rates of recrudescence following anti-malarial treatment are high. As use of substandard drugs, poor adherence, unusual pharmacokinetics, and inadequate immune responses are host characteristics, likely to pertain to each recurrence of infection, a small subgroup of patients provides the particular circumstances conducive to de-novo resistance selection and transmission. Conclusion Current dosing recommendations provide a resistance selection opportunity in those patients with low drug levels and high parasite burdens (often children or pregnant women. Patients with

  20. 1-{4-[(1-Isobutyl-1H-imidazo[4,5-c]quinolin-4ylamino]phenyl}ethanone

    Directory of Open Access Journals (Sweden)

    Dinesha

    2012-11-01

    Full Text Available The title compound (3 is synthesized by the nucleophilic substitution of 4-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline 2 with 4-amino acetophenone in n-butanol. Newly prepared imiquimod derivative (3 is characterized by IR, NMR and mass spectral data.

  1. B(HSO43: An efficient and recyclable catalyst for the preparation of substituted Friedländer quinoline synthesis

    Directory of Open Access Journals (Sweden)

    Saghanezhad Seyyed Jafar

    2013-01-01

    Full Text Available Substituted quinolines have been synthesized in the presence of catalytic amounts of boron sulfonic acid (BSA in solvent-free conditions. This methodology offers some advantages including high yield, short reaction time, low cost of the catalyst, green conditions by avoiding toxic solvents and recoverable catalyst.

  2. Noncovalent-bonded 1D-3D supramolecular architectures from 2-methylquinoline/quinoline with monocarboxylic acid and dicarboxylic acid

    Science.gov (United States)

    Gao, Xingjun; Jin, Shouwen; Jin, Li; Ye, XiangHang; Zheng, Lu; Li, JingWen; Jin, BinPeng; Wang, Daqi

    2014-10-01

    Studies concentrating on noncovalent weak interactions between the organic base of 2-methylquinoline/quinoline, and carboxylic acid derivatives have led to an increased understanding of the role 2-methylquinoline/quinoline have in binding with carboxylic acids. Here anhydrous multicomponent organic acid-base adducts of 2-methylquinoline/quinoline have been prepared with carboxylic acids that ranged from monocarboxylic acid to dicarboxylic acid such as p-nitrobenzoic acid, (4-chloro-phenoxy)-acetic acid, 4-hydroxy-benzoic acid, 5-bromosalicylic acid, 2,4-dihydroxybenzoic acid, α-ketoglutaric acid, and 4-nitrophthalic acid. The seven crystalline complexes were characterized by X-ray diffraction analysis, IR, m.p., and elemental analysis. These structures adopted the hetero supramolecular synthons. Analysis of the crystal packing of 1-7 suggests that there are Nsbnd H⋯O, Osbnd H⋯N, and Osbnd H⋯O hydrogen bonds (charge assisted or neutral) between the acid and quinoline moieties in the studied compounds. Except the classical hydrogen bonding interactions, the secondary propagating interactions also play important roles in structure extension. These weak interactions combined, these compounds displayed 1D-3D framework structure.

  3. 10-hydroxybenzo[h]quinoline: Switching between single and double-well proton transfer through structural modifications

    DEFF Research Database (Denmark)

    Hristova, S; Dobrikov, G; Kamounah, F. S.;

    2015-01-01

    Proton transfer in 10-hydroxybenzo[h]quinoline (HBQ) and structurally modified compounds was investigated experimentally (steady state UV-Vis absorption and emission spectroscopy, NMR and advanced chemometric techniques) and theoretically (DFT and TD-DFT M06-2X/TZVP calculations) in the ground an...

  4. Ruthenium-catalysed synthesis of 2- and 3-substituted quinolines from anilines and 1,3-diols

    DEFF Research Database (Denmark)

    Monrad, Rune Nygaard; Madsen, Robert

    2011-01-01

    A straightforward synthesis of substituted quinolines is described by cyclocondensation of anilines with 1,3-diols. The reaction proceeds in mesitylene solution with catalytic amounts of RuCl3·xH 2O, PBu3 and MgBr2·OEt2. The transformation does not require any stoichiometric additives and only...

  5. Quinoline-Substituted 10-(naphthalene-7-yl)anthracene Derivatives for Blue Fluorescent Organic Light-Emitting Diodes.

    Science.gov (United States)

    Kim, Chanwoo; Park, Soo Na; Lee, Seul Bee; Kim, Young Seok; Lee, Ho Won; Kim, Young Kwan; Yoon, Seung Soo

    2016-02-01

    In this study, we have designed and synthesized blue emitters based on quinoline-substituted 10-(naphthalene-7-yl)anthracene. Particularly, a material exhibited highly efficient blue electroluminescence with CIE coordinates of (0.15, 0.18). PMID:27433688

  6. Poor quality vital anti-malarials in Africa - an urgent neglected public health priority

    Directory of Open Access Journals (Sweden)

    Newton Paul N

    2011-12-01

    Full Text Available Abstract Background Plasmodium falciparum malaria remains a major public health problem. A vital component of malaria control rests on the availability of good quality artemisinin-derivative based combination therapy (ACT at the correct dose. However, there are increasing reports of poor quality anti-malarials in Africa. Methods Seven collections of artemisinin derivative monotherapies, ACT and halofantrine anti-malarials of suspicious quality were collected in 2002/10 in eleven African countries and in Asia en route to Africa. Packaging, chemical composition (high performance liquid chromatography, direct ionization mass spectrometry, X-ray diffractometry, stable isotope analysis and botanical investigations were performed. Results Counterfeit artesunate containing chloroquine, counterfeit dihydroartemisinin (DHA containing paracetamol (acetaminophen, counterfeit DHA-piperaquine containing sildenafil, counterfeit artemether-lumefantrine containing pyrimethamine, counterfeit halofantrine containing artemisinin, and substandard/counterfeit or degraded artesunate and artesunate+amodiaquine in eight countries are described. Pollen analysis was consistent with manufacture of counterfeits in eastern Asia. These data do not allow estimation of the frequency of poor quality anti-malarials in Africa. Conclusions Criminals are producing diverse harmful anti-malarial counterfeits with important public health consequences. The presence of artesunate monotherapy, substandard and/or degraded and counterfeit medicines containing sub-therapeutic amounts of unexpected anti-malarials will engender drug resistance. With the threatening spread of artemisinin resistance to Africa, much greater investment is required to ensure the quality of ACTs and removal of artemisinin monotherapies. The International Health Regulations may need to be invoked to counter these serious public health problems.

  7. In vitro antimalarial activity of extracts of some plants from a biological reserve in Costa Rica.

    Science.gov (United States)

    Chinchilla, Misael; Valerio, Idalia; Sánchez, Ronald; Mora, Víctor; Bagnarello, Vanessa; Martínez, Laura; Gonzalez, Antonieta; Vanegas, Juan Carlos; Apestegui, Alvaro

    2012-06-01

    Treatment with the usual antimalarial drugs, have induced parasite resistance, reinforcing the need to finding natural antimalarial components that would be found on plants from the forest. Therefore, we decided to look for these components in Costa Rican plants from a protected forest area. Fresh and dry extracts of roots, bark, leaves, flowers and fruits of 25 plants from a biological reserve in Costa Rica, Reserva Biol6gica Alberto Manuel Brenes (REBAMB), were studied in vitro for the presence of substances with antimalarial activity. By studying the inhibition of P berghei schizogony, we assessed the antimalarial activity of several plant extracts: Aphelandra aurantiaca, A. tridentata (Acanthaceae); Xanthosoma undipes (Araceae); Iriartea deltoidea (Arecaceae); Neurolaena lobata (Asteraceae); Senna papillosa, Pterocarpus hayessi, Lonchocarpus pentaphyllus (Fabaceae); Nectandra membranacea, Persea povedae, Cinamomum chavarrianum (Lauraceae); Hampea appendiculata (Malvaceae); Ruagea glabra, Guarea glabra (Meliaceae); Psidium guajava (Myrtaceae); Bocconia frutescens (Papaveraceae); Piper friedrichsthalii (Piperaceae); Clematis dioica (Ranunculaceae); Prunus annularis (Rosaceae); Siparuna thecaphora (Siparunaceae); Solanum arboreum, Witheringia solanacea (Solanaceae); Ticodendrum incognitum (Ticodendraceae); Heliocarpus appendiculatus (Tiliaceae) and Myriocarpa longipes (Urticaceae). We used different parts of the plants as well as fresh and dried extracts for testing IC50. The solid content of the extracts ranged from 1-71.9 microg/mL. The fresh extracts showed stronger activity than the dry ones. Since the plants showing the strongest antimalarial activity are very common in Central America, and some similar genera of these plants have shown positives results in South America, we considered important to present these findings for discussion. On the other hand, this is the first systematic study of this kind ever realized in a circumscribed and protected area of

  8. Substandard artemisinin-based antimalarial medicines in licensed retail pharmaceutical outlets in Ghana

    Directory of Open Access Journals (Sweden)

    M. El-Duah & K. Ofori-Kwakye

    2012-09-01

    Full Text Available Background & objectives: The artemisinin-based antimalarial medicines are first line medicines in the treatmentof severe and uncomplicated falciparum malaria. Numerous brands of these medicines manufactured in variouscountries are available in the Ghanaian market. The study was aimed at evaluating the authenticity and qualityof selected brands of artemisinin-based antimalarial medicines marketed in Ghana.Methods: In all, 14 artemisinin-based antimalarial medicines were purchased from pharmacies (P and licensedchemical shops (LCSs in the Kumasi metropolis, Ghana. Simple field tests based on colorimetry and thin layerchromatography were employed in determining the authenticity of the samples. Important quality assessmenttests, namely uniformity of mass, crushing strength, disintegration time, and the percentage content of activepharmaceutical ingredients (APIs were determined.Results: All the brands tested contained the stipulated APIs. Artesunate tablet AT2 failed the uniformity of masstest while artesunate tablets AT3 & AT4 as well as amodiaquine tablets AM4 & AM6 failed the crushing strengthtest. All the six artemether-lumefantrine tablet brands passed the uniformity of mass, crushing strength anddisintegration tests. Only artemether-lumefantrine tablet brand AL1 contained the correct amount of the drugs.The other 13 artemisinin products contained either a lower (underdose or higher (overdose amount of thespecified drug. Artesunate monotherapy tablets were readily available in pharmacies and licensed chemicalshops.Interpretation & conclusion: All the artemisinin-based medicines tested (except AL1 were of substandardquality. The results demonstrate the need for continuous monitoring and evaluation of the quality of artemisininbased antimalarials in the Ghanaian market. Also, the practice of artemisinin antimalarial monotherapy is prevalentin Ghana. Determined efforts should, therefore, be made to eradicate the practice to prevent the development

  9. Enol ethers as carbonyl surrogates in a modification of the Povarov synthesis of 3-aryl quinolines and their anti-Toxoplasma activity.

    Science.gov (United States)

    Brown, Carla E; McNulty, James; Bordón, Claudia; Yolken, Robert; Jones-Brando, Lorraine

    2016-07-01

    A novel method for the preparation of 2-carboxyl-3-aryl quinoline derivatives from anilines, ethyl glyoxalate and enol ethers as phenylacetaldehyde surrogates is reported. The three-component coupling reaction occurs rapidly under mild conditions in dichloromethane catalysed by TFA. The method allows a more direct access to 3-aryl quinolines, sidestepping issues encountered with phenylacetaldehyde derivatives. This chemistry was used to prepare quinolines with 3-diarylether functionality that showed low micromolar efficacy (IC50 range: 5-26 μM) against in vitro Toxoplasma gondii coupled with little or no cytotoxicity (TD50≥ 320 μM) towards the host cells. PMID:27256871

  10. Sorption phenomena of methanol on heat treated coal; Netsushori wo hodokoshita sekitan no methanol kyuchaku tokusei

    Energy Technology Data Exchange (ETDEWEB)

    Yasuda, H.; Kaiho, M.; Yamada, O.; Soneda, Y.; Kobayashi, M.; Makino, M. [National Institute for Resources and Environment, Tsukuba (Japan)

    1996-10-28

    Experiments were carried out to learn methanol sorption characteristics of heat-treated coal. When Taiheiyo coal is heat-treated at 125{degree}C, performed with a first methanol adsorption at 25{degree}C, and then desorption at 25{degree}C, a site with strong interaction with methanol and a site with relatively weak interaction are generated in test samples. A small amount of methanol remains in both sites. Then, when the methanol is desorbed at as low temperature as 70{degree}C, the methanol in the site with strong interaction remains as it has existed therein, but the methanol in the site with relatively weak interaction desorbs partially, hence the adsorption amount in a second adsorption at 25{degree}C increases. However, when desorption is performed at as high temperature as 125{degree}C, the methanol in the site with strong interaction also desorbs, resulting in increased adsorption heat in the second adsorption. The adsorption velocity drops, however. Existence of methanol in a site with strong interaction affects the adsorption velocity, but no effect is given by methanol in a site with weak interaction. 3 refs., 4 figs.

  11. Effect of methanol on winter rape seedlings

    OpenAIRE

    Stanisław Kaczmarczy; Robert M. Devlin; Irena I. Zbieć

    2013-01-01

    Oil seed rape seedlings which had been treated with 10-30% methanol grew faster, their yield of fresh matter exceeded that of untreated control plants by 102%, of dry matter by 80%. Although methanol did not affect the content of chlorophyll or carotene in the leaves, the overall pigment yield grew with the dry matter of one seedling. The biomass of rape leaves which had been sprayed with 10 or 20% methanol solutions was by 50-90% higher as compared to untreated plants. The activity of some ...

  12. Hydrogen Production from Methanol Using Corona Discharges

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Hydrogen production at room temperature from liquid methanol has been conductedusing corona discharge. The content of water in methanol solution has a significant effect on thisproduction. When water concentration increases from 1.0 % to 16.7 %, the methanol conversionrate changes from 0.196 to 0.284 mol/h. An important finding in this investigation is theformation of ethylene glycol as a major by-product. The yield of ethylene glycol is ranged from0.0045 to 0.0075 mol/h based on the water content.

  13. Quinoline and derivatives at a tar oil contaminated site: hydroxylated products as indicator for natural attenuation?

    Energy Technology Data Exchange (ETDEWEB)

    Anne-Kirsten Reineke; Thomas Goeen; Alfred Preiss; Juliane Hollender [RWTH Aachen, Aachen (Germany). Institute of Hygiene and Environmental Medicine

    2007-08-01

    LC-MS-MS analysis of groundwater of a tar oil contaminated site (a former coal mine and coking plant in Castrop-Rauxel, Germany) showed the occurrence of the N-heterocycles quinoline and isoquinoline as well as their hydroxylated and hydrogenated metabolites. The concentrations of the hydroxylated compounds, 2(1H)-quinolinone and 1(2H)-isoquinolinone, were significantly higher than those of the nonsubstituted parent compounds. Therefore, exclusive quantification of the parent compounds leads to an underestimation of the amount of N-heterocycles present in the groundwater. Microbial degradation experiments of quinoline and isoquinoline with aquifer material of the site as inocculum showed the formation of hydroxylated and hydrogenated products under sulfate-reducing conditions, the prevailing conditions in the field. However, since analyses of seven tar products showed that these compounds are also primary constituents, their detection in groundwater is found to be a nonsufficient indicator for the occurrence of biological natural attenuation processes. Instead, the ratio of hydroxylated to parent compound (R{sub metabolite}) is proposed as a useful indicator. We found that 65-83% of all groundwater samples showed R{sub metabolite} for 2(1H)-quinolinone, 1(2H)-isoquinolinone, 3,4-dihydro-2(1H)-quinolinone, and 3,4-dihydro-1(2H)-isoquinolinone, which was higher than the highest ratio found in tar products. With respect to the observed partition coefficient between tar oil and water of 3.5 for quinoline and isoquinoline and 0.3 for 2(1H)-quinolinone and 1(2H)-isoquinolinone, the ratio in groundwater would be approximately 10 times higher than the ratio in tar oil. When paying attention to these two parameters, 19-31% of groundwater samples exceed the highest tar oil ratio. This indicates that biological processes take place in the aquifer of the site and R{sub metabolite} is an applicable indicator for natural attenuation. 42 refs., 6 figs., 2 tabs.

  14. Synthesis and evaluation of antimalarial activity of curcumin derivatives; Sintese e avaliacao da atividade antimalarica de compostos derivados da curcumina

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, Patricia Ramos; Miguel, Fabio Balbino; Almeida, Mauro Vieira de; Couri, Mara Rubia Costa [Universidade Federal de Juiz de Fora (UFSJ), MG (Brazil). Instituto de Ciencias Exatas. Departamento de Quimica; Oliveira, Michael Eder de; Ferreira, Vanessa Viana; Guimaraes, Daniel Silqueira Martins; Lima, Aline Brito de; Barbosa, Camila de Souza; Oliveira, Mariana Amorim de; Almeida, Mauro Vieira de; Viana, Gustavo Henrique Ribeiro; Varotti, Fernando de Pilla, E-mail: varotti@ufsj.edu.br [Universidade Federal de Sao Joao Del Rei (UFSJ), MG (Brazil). Centro de Ciencias da Saude; and others

    2014-05-15

    ne of the main challenges in the development of new antimalarial drugs is to achieve a viable lead candidate with good pharmacokinetic properties. Curcumin has a broad range of biological activities, including antimalarial activity. Herein, we report the antimalarial activity of six curcumin derivatives (6-12) and an initial analysis of their pharmacokinetic properties. Five compounds have demonstrated potent activity against the P. falciparum in vitro (IC{sub 50} values ranging from 1.7 to 15.2 μg mL{sup -1}), with moderate or low cytotoxicity against the HeLa cell line. The substitution of the carbonyl group in 6 by a 2,4-dinitrophenylhydrazone group (to afford 11) increases the Selective Index. These preliminary results indicate curcumin derivatives as potential antimalarial compounds. (author)

  15. Case management of malaria fever in Cambodia: results from national anti-malarial outlet and household surveys

    Directory of Open Access Journals (Sweden)

    Littrell Megan

    2011-10-01

    Full Text Available Abstract Background Continued progress towards global reduction in morbidity and mortality due to malaria requires scale-up of effective case management with artemisinin-combination therapy (ACT. The first case of artemisinin resistance in Plasmodium falciparum was documented in western Cambodia. Spread of artemisinin resistance would threaten recent gains in global malaria control. As such, the anti-malarial market and malaria case management practices in Cambodia have global significance. Methods Nationally-representative household and outlet surveys were conducted in 2009 among areas in Cambodia with malaria risk. An anti-malarial audit was conducted among all public and private outlets with the potential to sell anti-malarials. Indicators on availability, price and relative volumes sold/distributed were calculated across types of anti-malarials and outlets. The household survey collected information about management of recent "malaria fevers." Case management in the public versus private sector, and anti-malarial treatment based on malaria diagnostic testing were examined. Results Most public outlets (85% and nearly half of private pharmacies, clinics and drug stores stock ACT. Oral artemisinin monotherapy was found in pharmacies/clinics (9%, drug stores (14%, mobile providers (4% and grocery stores (2%. Among total anti-malarial volumes sold/distributed nationally, 6% are artemisinin monotherapies and 72% are ACT. Only 45% of people with recent "malaria fever" reportedly receive a diagnostic test, and the most common treatment acquired is a drug cocktail containing no identifiable anti-malarial. A self-reported positive diagnostic test, particularly when received in the public sector, improves likelihood of receiving anti-malarial treatment. Nonetheless, anti-malarial treatment of reportedly positive cases is low among people who seek treatment exclusively in the public (61% and private (42% sectors. Conclusions While data on the anti-malarial

  16. Evaluation of antimalarial activity of leaves of Acokanthera schimperi and Croton macrostachyus against Plasmodium berghei in Swiss albino mice

    OpenAIRE

    Mohammed, Tigist; Erko, Berhanu; Giday, Mirutse

    2014-01-01

    Background Malaria is one of the most important tropical diseases and the greatest cause of hospitalization and death. Recurring problems of drug resistance are reinforcing the need for finding new antimalarial drugs. In this respect, natural plant products are the main sources of biologically active compounds and have potential for the development of novel antimalarial drugs. A study was conducted to evaluate extracts of the leaves of Croton macrostachyus and Acokanthera schimperi for their ...

  17. In vitro and in vivo anti-malarial activity of tigecycline, a glycylcycline antibiotic, in combination with chloroquine

    OpenAIRE

    Sahu, Rajnish; Walker, Larry A.; Tekwani, Babu L.

    2014-01-01

    Background Several antibiotics have shown promising anti-malarial effects and have been useful for malarial chemotherapy, particularly in combination with standard anti-malarial drugs. Tigecycline, a semi-synthetic derivative of minocycline with a unique and novel mechanism of action, is the first clinically available drug in a new class of glycylcycline antibiotics. Methods Tigecycline was tested in vitro against chloroquine (CQ)-sensitive (D6) and resistant strains (W2) of Plasmodium falcip...

  18. Monoclonal Antibodies That Recognize the Alkylation Signature of Antimalarial Ozonides OZ277 (Arterolane) and OZ439 (Artefenomel)

    OpenAIRE

    Jourdan, Joëlle; Matile, Hugues; Reift, Ellen; Biehlmaier, Oliver; Dong, Yuxiang; Wang, Xiaofang; Mäser, Pascal; Vennerstrom, Jonathan L.; Wittlin, Sergio

    2015-01-01

    The singular structure of artemisinin, with its embedded 1,2,4-trioxane heterocycle, has inspired the discovery of numerous semisynthetic artemisinin and structurally diverse synthetic peroxide antimalarials, including ozonides OZ277 (arterolane) and OZ439 (artefenomel). Despite the critical importance of artemisinin combination therapies (ACTs), the precise mode of action of peroxidic antimalarials is not fully understood. However, it has long been proposed that the peroxide bond in artemisi...

  19. Development of a Specific Monoclonal Antibody-Based ELISA to Measure the Artemether Content of Antimalarial Drugs

    OpenAIRE

    Suqin Guo; Yongliang Cui; Lishan He; Liang Zhang; Zhen Cao; Wei Zhang; Rui Zhang; Guiyu Tan; Baomin Wang; Liwang Cui

    2013-01-01

    Artemether is one of the artemisinin derivatives that are active ingredients in antimalarial drugs. Counterfeit and substandard antimalarial drugs have become a serious problem, which demands reliable analytical tools and implementation of strict regulation of drug quality. Structural similarity among artemisinin analogs is a challenge to develop immunoassays that are specific to artemisinin derivatives. To produce specific antibodies to artemether, we used microbial fermentation of artemethe...

  20. Production of methanol/DME from biomass

    DEFF Research Database (Denmark)

    Ahrenfeldt, Jesper; Henriksen, Ulrik Birk; Münster-Swendsen, Janus;

    types have been investigated in this project: • The Two-Stage Gasifier (Viking Gasifier), designed to produce a very clean gas to be used in a gas engine, has been connected to a lab-scale methanol plant, to prove that the gas from the gasifier could be used for methanol production with a minimum of gas...... cleaning. This was proved by experiments. Thermodynamic computer models of DME and methanol plants based on using the Two-Stage Gasification concept were created to show the potential of such plants. The models showed that the potential biomass to DME/methanol + net electricity energy efficiency was 51...... of these different methods to provide biomass based transport fuels has shown that the gasification based route is an attractive and efficient technology....

  1. Methanol gasoline blend from petroleum coke sources

    Energy Technology Data Exchange (ETDEWEB)

    Netzer, David [Consulting Chemical Engineer (United States); Wallsgrove, Chris [Process Engineering Manager (United States)

    2011-07-01

    In Alberta, a large amount of petroleum coke is produced as a byproduct from processes relating to bitumen upgrading and refining. Unfortunately, there is little to no market for this product in the province. This presentation addresses concerns relating to the concept of converting the otherwise wasted petcoke into methanol and using it as a blending component in gasoline. The presentation tackles issues relating to environmental impact, economics, renewability, toxicity, safety, and vehicle design by analyzing and comparing the proposed methanol/gasoline (M-10) to that of an ethanol/gasoline (E-10). The presentation covers analysis of the CO2 emissions, an analysis of the finances, and a number of scenarios involving the improper use or accidental spillage of M-10. Through the comparison of methanol/gasoline and ethanol/gasoline, the presentation demonstrated that converting the petcoke byproduct into methanol for use as a gasoline blend is a viable option.

  2. Quiet Changes in the Methanol Supply Mode

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ The coal chemicals sector, the new coal chemicals sector in particular, has been emerging fast in China in recent years. The production scale of methanol as an important coal chemical product has expanded constantly.

  3. Investigations into low pressure methanol synthesis

    DEFF Research Database (Denmark)

    Sharafutdinov, Irek

    The central topic of this work has been synthesis, characterization and optimization of novel Ni-Ga based catalysts for hydrogenation of CO2 to methanol. The overall goal was to search for materials that could be used as a low temperature (and low pressure) methanol synthesis catalyst....... This is required for small scale delocalized methanol production sites, where installation of energy demanding compression units should be avoided. The work was triggered by DFT calculations, which showed that certain bimetallic systems are active towards methanol synthesis from CO2 and H2 at ambient pressure....... Among them, Ni-Ga has been chosen, primarily due to low price of constituent metals. After the preliminary optimization work, an optimal catalyst composition and preparation method has been suggested. Indeed, for an optimal catalyst, which is a SiO2 supported Ni-Ga prepared from a solution of nitrates...

  4. Silicon Based Direct Methanol Fuel Cells

    OpenAIRE

    Larsen, Jackie Vincent; Thomsen, Erik Vilain

    2013-01-01

    The purpose of this project has been to investigate and fabricate small scale Micro Direct Methanol Fuel Cells (μDMFC). They are investigated as a possible alternative for Zinc-air batteries in small size consumer devices such as hearing aids. In such devices the conventional rechargeable batteries such as lithium-ion batteries have insufficiently low energy density. Methanol is a promising fuel for such devices due to the high energy density and ease of refueling compared to charging batteri...

  5. Potential of methanol in dual fuel combustion

    OpenAIRE

    Tuominen, Tino

    2016-01-01

    Depleting oil resources together with the climate change due to the use of fossil fuels are motivating to investigate alternative fuels and new combustion strategies used with them. At the moment, dual fuel combustion is one of the most promising new combustion strategies. Combining it to the use of renewable methanol as a primary fuel, it offers an interesting option for the conventional combustion engine. This thesis focuses on investigating the theoretical potential of methanol in dua...

  6. Excess Transport Properties of Binary Mixtures of Quinoline with Xylenes at Different Temperatures

    Directory of Open Access Journals (Sweden)

    Sk. Fakruddin

    2012-01-01

    Full Text Available The ultrasonic velocity and density of binary liquid mixtures of quinoline with o-xylene, m-xylene, and p-xylene have been measured over the entire range of composition at = 303.15, 308.15, 313.15, and 318.15 K. Using these data, various parameters like adiabatic compressibility (β, intermolecular free length (, and acoustic impedance ( and some excess parameters like excess adiabatic compressibility (, excess intermolecular free length (, excess acoustic impedance (, and excess ultrasonic velocity ( have been calculated for all the three mixtures. The calculated deviations and excess functions have been fitted to Redlich-Kister polynomial equation. The observed deviations have been explained on the basis of the intermolecular interactions present in these mixtures.

  7. Deuterium isotope effects on 13C chemical shifts of 10-Hydroxybenzo[h]quinolines

    DEFF Research Database (Denmark)

    Hansen, Poul Erik; Kamounah, Fadhil S.; Gryko, Daniel T.

    2013-01-01

    Deuterium isotope effects on 13C-NMR chemical shifts are investigated in a series of 10-hydroxybenzo[h]quinolines (HBQ’s) The OH proton is deuteriated. The isotope effects on 13C chemical shifts in these hydrogen bonded systems are rather unusual. The formal four-bond effects are found...... to be negative, indicating transmission via the hydrogen bond. In addition unusual long-range effects are seen. Structures, NMR chemical shifts and changes in nuclear shieldings upon deuteriation are calculated using DFT methods. Two-bond deuterium isotope effects on 13C chemical shifts are correlated...... with calculated OH stretching frequencies. Isotope effects on chemical shifts are calculated for systems with OH exchanged by OD. Hydrogen bond potentials are discussed. New and more soluble nitro derivatives are synthesized....

  8. A fluorescence turn-on chemosensor for hydrogen sulfate anion based on quinoline and naphthalimide.

    Science.gov (United States)

    Luo, Zaoli; Yin, Kai; Yu, Zhu; Chen, Mengxue; Li, Yan; Ren, Jun

    2016-12-01

    A new fluorescence turn-on chemosensor 1 based on quinoline and naphthalimide was prepared and its anion sensing toward various anions behavior was explored in this paper. Sensor 1 exhibited a highly selective fluorescent response toward HSO4(-) with an 8-fold fluorescence intensity enhancement in the presence of 10equiv. of HSO4(-) in DMSO-H2O (1/1, v/v) solution. The sensor also displayed high sensitivity to hydrogen sulfate and the detection limit was calculated to be 7.79×10(-7)M. The sensing mechanism has been suggested to proceed via a hydrolysis process of the Schiff base group. The hydrolysis product has been isolated and further identified by (1)H NMR and MS. PMID:27323316

  9. Fluorescence in complexes based on quinolines-derivatives: a search for better fluorescent probes.

    Science.gov (United States)

    Mecca, Carolina Z P; Fonseca, Fernando L A; Bagatin, Izilda A

    2016-11-01

    Quinoline-derived fluorescent complexes were designed; synthesized by the reaction of 5-nitro-8-hydroxyquinoline and 5-chloro-8-hydroxyquinoline with Al(3+), Mg(2+), Zn(2+), and Cd(2+) salts (1-8); and characterized. The (1)H NMR spectra of complexes 1 and 5, containing Al(3+), were consistent with an octahedral structure having approximate D3 symmetry, and the results supported the favored facial isomer (fac). Data for complexes 2-4 and 6-8 supported the formation of tetrahedral structures. Intense luminescence was detected for complexes 5-8, even with the naked eye, as indicated by quantum yield values of 0.087, 0.094, 0.051, and 0.021, respectively. Furthermore, in contrast to 5-nitro-8-hydroxyquinoline, the 5-chloro-8-hydroxyquinoline ligand exhibited bands at different energies depending on the coordinated metal, which supported its potential application in ionic and biological probes, as well as in cell imaging. PMID:27288961

  10. Second-order optical effects in several pyrazolo-quinoline derivatives

    Science.gov (United States)

    Makowska-Janusik, M.; Gondek, E.; Kityk, I. V.; Wisła, J.; Sanetra, J.; Danel, A.

    2004-11-01

    Using optical poling of several pyazolo-quinoline (PAQ) derivatives we have found an existence of sufficiently high second order optical susceptibility at wavelength 1.76 μm varying in the range 0.9-2.8 pm/V. The performed quantum chemical simulations of the UV-absorption for isolated, solvated and incorporated into the polymethacrylate (PMMA) polymer films have shown that the PM3 method is the best among the semi-empirical ones to simulate the optical properties. The calculations of the hyperpolarizabilites have shown a good correlation with experimentally measured susceptibilities obtained from the optical poling. We have found that experimental susceptibility depends on linear molecular polarizability and photoinducing changes of the molecular dipole moment. It is clearly seen for the PAQ4-PAQ6 molecules possessing halogen atoms with relatively large polarizabilities.

  11. Second-order optical effects in several pyrazolo-quinoline derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Makowska-Janusik, M. [Solid State Department, Institute of Physics, WSP Czestochowa, Al. Armii Krajowej 13/15, Czestochowa PL42201 (Poland); Gondek, E. [Institute of Physics, Cracow University of Technology, ul. Podchorazych 1, 30-084 (Poland); Kityk, I.V. [Department of Biology and Biophysics, Technical University of Czestochowa, Al. Armii Krajowej 36, Czestochowa PL-42210 (Poland)]. E-mail: i.kityk@wsp.czest.pl; WisIa, J. [Departament of Chemistry, Hugon Kollataj Agricultural University, Al. Mickiewicza 24/28, 30-059 Cracow (Poland); Sanetra, J. [Institute of Physics, Cracow University of Technology, ul. Podchorazych 1, 30-084 (Poland); Danel, A. [Department of Chemistry, Hugon Kollataj Agricultural University, Al. Mickiewicza 24/28, 30-059 Cracow (Poland)

    2004-11-15

    Using optical poling of several pyazolo-quinoline (PAQ) derivatives we have found an existence of sufficiently high second order optical susceptibility at wavelength 1.76 {mu}m varying in the range 0.9-2.8 pm/V. The performed quantum chemical simulations of the UV-absorption for isolated, solvated and incorporated into the polymethacrylate (PMMA) polymer films have shown that the PM3 method is the best among the semi-empirical ones to simulate the optical properties. The calculations of the hyperpolarizabilites have shown a good correlation with experimentally measured susceptibilities obtained from the optical poling. We have found that experimental susceptibility depends on linear molecular polarizability and photoinducing changes of the molecular dipole moment. It is clearly seen for the PAQ4-PAQ6 molecules possessing halogen atoms with relatively large polarizabilities.

  12. Transesterification of waste vegetable oil under pulse sonication using ethanol, methanol and ethanol–methanol mixtures

    International Nuclear Information System (INIS)

    Highlights: • Pulse sonication effect on transesterification of waste vegetable oil was studied. • Effects of ethanol, methanol, and alcohol mixtures on FAMEs yield were evaluated. • Effect of ultrasonic intensity, power density, and its output rates were evaluated. • Alcohol mixtures resulted in higher biodiesel yields due to better solubility. - Abstract: This study reports on the effects of direct pulse sonication and the type of alcohol (methanol and ethanol) on the transesterification reaction of waste vegetable oil without any external heating or mechanical mixing. Biodiesel yields and optimum process conditions for the transesterification reaction involving ethanol, methanol, and ethanol–methanol mixtures were evaluated. The effects of ultrasonic power densities (by varying sample volumes), power output rates (in W), and ultrasonic intensities (by varying the reactor size) were studied for transesterification reaction with ethanol, methanol and ethanol–methanol (50%-50%) mixtures. The optimum process conditions for ethanol or methanol based transesterification reaction of waste vegetable oil were determined as: 9:1 alcohol to oil ratio, 1% wt. catalyst amount, 1–2 min reaction time at a power output rate between 75 and 150 W. It was shown that the transesterification reactions using ethanol–methanol mixtures resulted in biodiesel yields as high as >99% at lower power density and ultrasound intensity when compared to ethanol or methanol based transesterification reactions

  13. SYNTHESIS AND EVALUATION OF ANTIMICROBIAL ACTIVITY OF 1-BENZOYL-1H-PYRAZOLO [4,3-C]QUINOLIN-4(5H-ONES

    Directory of Open Access Journals (Sweden)

    Shivashankar Murugesh

    2011-01-01

    Full Text Available A series of 1-benzoyl-1H-pyrazolo [4,3-C]quinolin-4(5H-one, carrying appropriate substituents at the Quinoline ring have been synthesized in good yields via the condensation of 4-chloro-3-formylquinolin-2[1H]ones with benzohydrazide using triethylamine as a base. All the synthesized compounds were evaluated for their antibacterial activities.

  14. Efficient One-pot Synthesis of Pyrrolo[2,1-a]isoquinoline and Pyrrolo[1,2-a]quinoline Derivatives

    Institute of Scientific and Technical Information of China (English)

    LIU Zhen-ming; WU Lei; SUN Jing; YAN Chao-guo

    2012-01-01

    A one-pot sequential reaction for efficient synthesis of pyrrolo[2,1-a]isoquinoline and pyrrolo[1,2-a]-quinoline derivatives has been developed.The reaction included firstly the Cu-catalyzed three-component reaction of isoquinoline(quinoline),acetylenedicarboxylate and alkynylbenzene and then Cs2CO3-promoted intramolecular cyclization reaction of initially formed 1-alkeny1-2-alkynyl-1,2-dihydroisoquinoline(1,2-dihydroquinoline).

  15. Molecular iodine catalyzed synthesis of tetrazolo[1,5-a]-quinoline based imidazoles as a new class of antimicrobial and antituberculosis agents

    Institute of Scientific and Technical Information of China (English)

    Divyesh C. Mungra; Harshad G. Kathrotiya; Niraj K. Ladani; Manish P. Patel; Ranjan G. Patel

    2012-01-01

    A series of some new tetrazolo[1,5-a]quinoline based tetrasubstituted imidazole derivatives 6a-I have been synthesized by a reaction of tetrazolo[1,5-a]quinoline-4-carbaldehyde 3a-d,benzil 4,aromatic amine 5a-c and ammonium acetate in the presence of iodine through one-pot multi-component reaction (MCR) approach.All the derivatives were screened for antimicrobial and antituberculosis activities and results worth further investigations.

  16. Photocytotoxicity of a 5-nitrofuran-ethenyl-quinoline antiseptic (Quinifuryl to P388 mouse leukemia cells

    Directory of Open Access Journals (Sweden)

    Daghastanli N.A.

    2004-01-01

    Full Text Available Quinifuryl (MW 449.52, 2-(5'-nitro-2'-furanylethenyl-4-{N-[4'-(N,N-diethylamino-1'-methylbutyl]carbamoyl} quinoline, is a water soluble representative of a family of 5-nitrofuran-ethenyl-quinoline drugs which has been shown to be highly toxic to various lines of transformed cells in the dark. In the present study, the toxicity of Quinifuryl to P388 mouse leukemia cells was compared in the dark and under illumination with visible light (390-500 nm. Illumination of water solutions of Quinifuryl (at concentrations ranging from 0.09 to 9.0 µg/ml in the presence of P388 cells resulted in its photodecomposition and was accompanied by elevated cytotoxicity. A significant capacity to kill P388 cells was detected at a drug concentration as low as 0.09 µg/ml. The toxic effect detected at this drug concentration under illumination exceeded the effect observed in the dark by more than three times. Moreover, the general toxic effect of Quinifuryl, which included cell proliferation arrest, was nearly 100%. Both dose- and time-dependent toxic effects were measured under illumination. The LC50 value of Quinifuryl during incubation with P388 cells was ~0.45 µg/ml under illumination for 60 min and >12 µg/ml in the dark. We have demonstrated that the final products of the Quinifuryl photolysis are not toxic, which means that the short-lived intermediates of Quinifuryl photodecomposition are responsible for the phototoxicity of this compound. The data obtained in the present study are the first to indicate photocytotoxicity of a nitroheterocyclic compound and demonstrate the possibility of its application as a photosensitizer drug for photochemotherapy.

  17. On the molecular basis of the activity of the antimalarial drug chloroquine: EXAFS-assisted DFT evidence of a direct Fe-N bond with free heme in solution

    Science.gov (United States)

    Macetti, Giovanni; Rizzato, Silvia; Beghi, Fabio; Silvestrini, Lucia; Lo Presti, Leonardo

    2016-02-01

    4-aminoquinoline antiplasmodials interfere with the biocrystallization of the malaria pigment, a key step of the malaria parasite metabolism. It is commonly believed that these drugs set stacking π···π interactions with the Fe-protoporphyrin scaffold of the free heme, even though the details of the heme:drug recognition process remain elusive. In this work, the local coordination of Fe(III) ions in acidic solutions of hematin at room temperature was investigated by extended x-ray absorption fine structure (EXAFS) spectroscopy in the 4.0-5.5 pH range, both in the presence and in the absence of the antimalarial drug chloroquine. EXAFS results were complemented by DFT simulations in polarizable continuum media to model solvent effects. We found evidence that a complex where the drug quinoline nitrogen is coordinated with the iron center might coexist with formerly proposed adduct geometries, based on stacking interactions. Charge-assisted hydrogen bonds among lateral chains of the two molecules play a crucial role in stabilizing this complex, whose formation is favored by the presence of lipid micelles. The direct Fe-N bond could reversibly block the axial position in the Fe 1st coordination shell in free heme, acting as an inhibitor for the crystallization of the malaria pigment without permanently hampering the catalytic activity of the redox center. These findings are discussed in the light of possible implications on the engineering of drugs able to thwart the adaptability of the malaria parasite against classical aminoquinoline-based therapies.

  18. Stage-specific activity of potential antimalarial compounds measured in vitro by flow cytometry in comparison to optical microscopy and hypoxanthine uptake

    Directory of Open Access Journals (Sweden)

    Carmen E Contreras

    2004-03-01

    Full Text Available The evaluation of new antimalarial agents using older methods of monitoring sensitivity to antimalarial drugs are laborious and poorly suited to discriminate stage-specific activity. We used flow cytometry to study the effect of established antimalarial compounds, cysteine protease inhibitors, and a quinolone against asexual stages of Plasmodium falciparum. Cultured P. falciparum parasites were treated for 48 h with different drug concentrations and the parasitemia was determined by flow cytometry methods after DNA staining with propidium iodide. P. falciparum erythrocytic life cycle stages were readily distinguished by flow cytometry. Activities of established and new antimalarial compounds measured by flow cytometry were equivalent to results obtained with microscopy and metabolite uptake assays. The antimalarial activity of all compounds was higher against P. falciparum trophozoite stages. Advantages of flow cytometry analysis over traditional assays included higher throughput for data collection, insight into the stage-specificity of antimalarial activity avoiding use of radioactive isotopes.

  19. Quinolinic Acid Responses during Interferon-α-Induced Depressive Symptomatology in Patients with Chronic Hepatitis C Infection - A Novel Aspect for Depression and Inflammatory Hypothesis

    Science.gov (United States)

    Baranyi, Andreas; Meinitzer, Andreas; Breitenecker, Robert J.; Amouzadeh-Ghadikolai, Omid; Stauber, Rudolf; Rothenhäusler, Hans-Bernd

    2015-01-01

    Background The aim of this exploratory study is to gain for the first time a more comprehensive picture of the impact of changes of quinolinic acid concentrations on depressive symptomatology during and after IFN-α therapy. Methods The quinolinic acid concentrations of 35 HCV patients are examined in a prospective survey over the entire period of IFN-α treatment as well as three months later at six different times (baseline, one, three, six and nine months after the beginning of IFN-α treatment, and after the end of treatment). Results During IFN-α treatment Hamilton Depression Rating Scale scores rise significantly. At the same time there is greater activity of indoleamine 2,3-dioxygenase, with a resulting increase in plasma kynurenine concentrations. Compared to baseline values quinolinic acid concentrations increase significantly during therapy, reflecting an increased neurotoxic challenge. In addition, patients with higher scores in the Hamilton Depression Rating Scale at six and nine months after starting therapy show significantly higher levels of quinolinic acid concentration. Conclusions The increase of quinolinic acid during IFN-α therapy might contribute to depressive symptomatology through the neurotoxic challenge caused by quinolinic acid. Subsequently, our exploratory study results support the inflammatory hypothesis of depression. The awareness of relevant risk factors of IFN-α treatment-induced depression is essential to develop preventative treatment strategies. PMID:26368809

  20. Effect of 8-hydroxy-, 8-mercapto- and 5-chloro-7-iodo-8-hydroxy-quinoline on the uptake and distribution of nickel in mice

    Energy Technology Data Exchange (ETDEWEB)

    Borg-Neczak, K.; Tjaelve, H. (Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala Biomedical Centre, Uppsala (Sweden))

    1994-01-01

    Oral administration of Ni[sup 2+] together with 8-hydroxyquinoline (8-OH-quinoline), 8-mercaptoquinoline (8-SH-quinoline) or 5-chloro-7-iodo-8-hydroxyquinoline (clioquinol) resulted in increased tissue levels of the metal in several tissues of mice in comparison with animals given the Ni[sup 2+] alone. Ni[sup 2+] forms lipophilic complexes with these compounds and it can be assumed that this will facilitate the uptake of Ni[sup 2+] over the walls of the gastrointestinal tract. Our results showed that 8-SH-quinoline, in contrast to 8-OH-quinoline and clioquinol, induces a markedly changed distribution pattern of the Ni[sup 2+] in the body, with uptake of the metal in tissues such as the central nervous system, pigmented tissues, the pancreatic islets and the thyroid. It is probable that the Ni[sup 2+] -complex with 8-SH-quinoline is stable enough to persist for a time period in the tissues and that the obtained pattern partly reflects the distribution of the complexed metal. In contrast, following the absorption from the gastrointestinal tract there may be a dissociation of the complexes between Ni[sup 2+] and 8-OH-quinoline or clioquinol, resulting in increased metal levels in various tissues, but with similar distribution as when the Ni[sup 2+] is given alone. (au) (21 refs.).

  1. Screening of the antimalarial activity of plants of the Cucurbitaceae family

    Directory of Open Access Journals (Sweden)

    Cláudia Zuany Amorim

    1991-01-01

    Full Text Available Crude ethanolic extracts (CEEs from two species of Cucurbitaceae, Cucurbita maxima and Momordica charantia (commonly called "abóbora moranga" and melão de São Caetano", respectively were assayed for antimalarial activity by the 4-d suppressive test. The CEE of dry C. maxima seeds showed strong antimalarial activity following oral administration (259 and 500 mg/kg, reducing by 50% the levels of parasistemia in Plasmodium berghey-infected mice. Treatment of normal animals with 500 mg/Kg of the extract three days before intravenous injection of P. berghei caused a significant 30% reduction in parasitemic levels. No effect was observed when the animals were treated with the CEE only on the day of inoculation. Oral administration of the CEE of dry M. charantia leaves adminstered orally was ineffective up to 500 mg/Kg in lowering the parasitemic levels of malarious mice.

  2. In vitro inhibition of Plasmodium falciparum by substances isolated from Amazonian antimalarial plants

    Directory of Open Access Journals (Sweden)

    Valter F de Andrade-Neto

    2007-06-01

    Full Text Available In the present study, a quassinoid, neosergeolide, isolated from the roots and stems of Picrolemma sprucei (Simaroubaceae, the indole alkaloids ellipticine and aspidocarpine, isolated from the bark of Aspidosperma vargasii and A. desmanthum (Apocynaceae, respectively, and 4-nerolidylcatechol, isolated from the roots of Pothomorphe peltata (Piperaceae, all presented significant in vitro inhibition (more active than quinine and chloroquine of the multi-drug resistant K1 strain of Plasmodium falciparum. Neosergeolide presented activity in the nanomolar range. This is the first report on the antimalarial activity of these known, natural compounds. This is also the first report on the isolation of aspidocarpine from A. desmanthum. These compounds are good candidates for pre-clinical tests as novel lead structures with the aim of finding new antimalarial prototypes and lend support to the traditional use of the plants from which these compounds are derived.

  3. Detection of In Vitro Antimalarial Activity of Some Myanmar Medicinal Plants

    International Nuclear Information System (INIS)

    In order to find out the novel effective antimalarials. six medicinal plants, namely Erythrina stricta Roxb. (Kathit), Luffa acutangula Roxb. (Thabut - Kja), Cordia rothii Roem. and Schult. (Thanet), Tribulus terrestris Linn. (Sule). Zizphus oenoplia Mill. (Paung - pe) and Mimusops elengi Roxb. (Khaye) were selected and tested for their antimalarial activity by using in vitro microdilution technique. According to the in vitro test results, Erythrina stricta Roxb. (Kathit) was found to possess significant suppressive effect on Plasmodium falciparum. With the serially diluted extract dosage concentrations ranging from 1.250 ng/ml to 40,000 ng/ml, the schizont suppressive percentage of Eryhrina stricta Roxb. (Kathi) was observed to be 19.57%, 35.44%, 55.18%, 96.04%,100% and 100% respectively

  4. Production of methanol/DME from biomass

    Energy Technology Data Exchange (ETDEWEB)

    Ahrenfeldt, J.; Birk Henriksen, U.; Muenster-Swendsen, J.; Fink, A.; Roengaard Clausen, L.; Munkholt Christensen, J.; Qin, K.; Lin, W.; Arendt Jensen, P.; Degn Jensen, A.

    2011-07-01

    In this project the production of DME/methanol from biomass has been investigated. Production of DME/methanol from biomass requires the use of a gasifier to transform the solid fuel to a synthesis gas (syngas) - this syngas can then be catalytically converted to DME/methanol. Two different gasifier types have been investigated in this project: 1) The Two-Stage Gasifier (Viking Gasifier), designed to produce a very clean gas to be used in a gas engine, has been connected to a lab-scale methanol plant, to prove that the gas from the gasifier could be used for methanol production with a minimum of gas cleaning. This was proved by experiments. Thermodynamic computer models of DME and methanol plants based on using the Two-Stage Gasification concept were created to show the potential of such plants. The models showed that the potential biomass to DME/methanol + net electricity energy efficiency was 51-58% (LHV). By using waste heat from the plants for district heating, the total energy efficiencies could reach 87-88% (LHV). 2) A lab-scale electrically heated entrained flow gasifier has been used to gasify wood and straw. Entrained flow gasifiers are today the preferred gasifier type for commercial coal gasification, but little information exists on using these types of gasifiers for biomass gasification. The experiments performed provided quantitative data on product and gas composition as a function of operation conditions. Biomass can be gasified with less oxygen consumption compared to coal. The organic fraction of the biomass that is not converted to gas appears as soot. Thermodynamic computer models of DME and methanol plants based on using entrained flow gasification were created to show the potential of such plants. These models showed that the potential torrefied biomass to DME/methanol + net electricity energy efficiency was 65-71% (LHV). Different routes to produce liquid transport fuels from biomass are possible. They include production of RME (rapeseed oil

  5. Novel Inhibitors of Plasmodium falciparum Dihydroorotate Dehydrogenase with Anti-malarial Activity in the Mouse Model*

    OpenAIRE

    Booker, Michael L.; Bastos, Cecilia M.; Kramer, Martin L.; Barker, Robert H.; Skerlj, Renato; Sidhu, Amar Bir; Deng, Xiaoyi; Celatka, Cassandra; Cortese, Joseph F.; Guerrero Bravo, Jose E.; Crespo Llado, Keila N.; Serrano, Adelfa E.; Angulo-Barturen, Iñigo; Jiménez-Díaz, María Belén; Viera, Sara

    2010-01-01

    Plasmodium falciparum, the causative agent of the most deadly form of human malaria, is unable to salvage pyrimidines and must rely on de novo biosynthesis for survival. Dihydroorotate dehydrogenase (DHODH) catalyzes the rate-limiting step in the pyrimidine biosynthetic pathway and represents a potential target for anti-malarial therapy. A high throughput screen and subsequent medicinal chemistry program identified a series of N-alkyl-5-(1H-benzimidazol-1-yl)thiophene-2-carboxamides with low ...

  6. ANTIMALARIAL DRUGS IN THERAPY OF SYSTEMIC LUPUS ERYTHEMATOSUS: PAST, PRESENT, FUTURE

    Directory of Open Access Journals (Sweden)

    Tatyana Andreyevna Lisitsyna

    2010-01-01

    Full Text Available The data available in the literature on experience in using antimalarial drugs in the treatment of systemic lupus erythematosus are summarized. A major emphasis is placed on therapy with hydroxychlorochine (plaquenil versus chlorine. Possible mechanisms of action of the drug and its effect on the course of the disease itself and concomitant abnormalities are described. Data on the toxicity of the drug and its safe use in pregnancy and lactation are also discussed

  7. Surveillance of antimalarial drug resistance in China in the 1980s–1990s

    OpenAIRE

    Liu, De-Quan

    2014-01-01

    Since the successful preparation of the microplates and the medium for field application, the resistance degree and its geographical distribution of chloroquine-resistant Plasmodium falciparum, the fluctuation of the resistance degree of P. falciparum to chloroquine, and the sensitivity of the parasite to commonly used antimalarial drugs were investigated between 1980 and 2003 by the in vitro microtest and the in vivo four-week test recommended by the World Health Organization (WHO). The resu...

  8. A genome wide association study of Plasmodium falciparum susceptibility to 22 antimalarial drugs in Kenya.

    Directory of Open Access Journals (Sweden)

    Jason P Wendler

    Full Text Available BACKGROUND: Drug resistance remains a chief concern for malaria control. In order to determine the genetic markers of drug resistant parasites, we tested the genome-wide associations (GWA of sequence-based genotypes from 35 Kenyan P. falciparum parasites with the activities of 22 antimalarial drugs. METHODS AND PRINCIPAL FINDINGS: Parasites isolated from children with acute febrile malaria were adapted to culture, and sensitivity was determined by in vitro growth in the presence of anti-malarial drugs. Parasites were genotyped using whole genome sequencing techniques. Associations between 6250 single nucleotide polymorphisms (SNPs and resistance to individual anti-malarial agents were determined, with false discovery rate adjustment for multiple hypothesis testing. We identified expected associations in the pfcrt region with chloroquine (CQ activity, and other novel loci associated with amodiaquine, quinazoline, and quinine activities. Signals for CQ and primaquine (PQ overlap in and around pfcrt, and interestingly the phenotypes are inversely related for these two drugs. We catalog the variation in dhfr, dhps, mdr1, nhe, and crt, including novel SNPs, and confirm the presence of a dhfr-164L quadruple mutant in coastal Kenya. Mutations implicated in sulfadoxine-pyrimethamine resistance are at or near fixation in this sample set. CONCLUSIONS/SIGNIFICANCE: Sequence-based GWA studies are powerful tools for phenotypic association tests. Using this approach on falciparum parasites from coastal Kenya we identified known and previously unreported genes associated with phenotypic resistance to anti-malarial drugs, and observe in high-resolution haplotype visualizations a possible signature of an inverse selective relationship between CQ and PQ.

  9. Medicines informal market in Congo, Burundi and Angola: counterfeit and sub-standard antimalarials

    OpenAIRE

    Bertocchi Paola; Antoniella Eleonora; Cocchieri Emilia; Di Maggio Anna; Gaudiano Maria; Alimonti Stefano; Valvo Luisa

    2007-01-01

    Abstract Background The presence of counterfeits and sub-standards in African medicines market is a dramatic problem that causes many deaths each year. The increase of the phenomenon of pharmaceutical counterfeiting is due to the rise of the illegal market and to the impossibility to purchase branded high cost medicines. Methods In this paper the results of a quality control on antimalarial tablet samples purchased in the informal market in Congo, Burundi and Angola are reported. The quality ...

  10. Antimalarial Chemotherapy: Natural Product Inspired Development of Preclinical and Clinical Candidates with Diverse Mechanisms of Action.

    Science.gov (United States)

    Fernández-Álvaro, Elena; Hong, W David; Nixon, Gemma L; O'Neill, Paul M; Calderón, Félix

    2016-06-23

    Natural products have played a pivotal role in malaria chemotherapy progressing from quinine and artemisinin to ozonide-based compounds. Many of these natural products have served as template for the design and development of antimalarial drugs currently in the clinic or in the development phase. In this review, we will detail those privileged scaffolds that have guided medicinal chemistry efforts yielding molecules that have reached the clinic. PMID:26791529

  11. Synthesis and in vitro antimalarial activity of novel chalcone derivatives / Frans Johannes Smit

    OpenAIRE

    Smit, Frans Johannes

    2014-01-01

    Malaria is endemic in 106 countries worldwide. This disease is caused by a parasite from the genus Plasmodium. Of the five species that infect humans, Plasmodium falciparum is the most virulent, with over three billion people at risk and around 660 000 deaths reported in 2011. Of these deaths, 91% were in the African region, while 86% were children under the age of five. In light of the widespread development of resistance by malaria parasites against the classic antimalarial drugs, such as c...

  12. Amazonian plant natural products:perspectives for discovery of new antimalarial drug leads

    OpenAIRE

    Lucio H Freitas-Junior; Pedro Cravo; Marcus Vinícius Guimarães Lacerda; André Machado Siqueira; Carolina Borsoi Moraes; Gina Frausin; Luiz Francisco Rocha e Silva; Stefanie Costa Pinto Lopes; Renata Braga Souza Lima; Fabio Trindade Maranhão Costa; Adrian Martin Pohlit

    2013-01-01

    Plasmodium falciparum and P. vivax malaria parasites are now resistant, or showing signs of resistance, to most drugs used in therapy. Novel chemical entities that exhibit new mechanisms of antiplasmodial action are needed. New antimalarials that block transmission of Plasmodium spp. from humans to Anopheles mosquito vectors are key to malaria eradication efforts. Although P. vivax causes a considerable number of malaria cases, its importance has for long been neglected. Vivax malaria can cau...

  13. ANTIMALARIAL DRUGS IN THERAPY OF SYSTEMIC LUPUS ERYTHEMATOSUS: PAST, PRESENT, FUTURE

    OpenAIRE

    Tatyana Andreyevna Lisitsyna; N. M. Kosheleva

    2010-01-01

    The data available in the literature on experience in using antimalarial drugs in the treatment of systemic lupus erythematosus are summarized. A major emphasis is placed on therapy with hydroxychlorochine (plaquenil) versus chlorine. Possible mechanisms of action of the drug and its effect on the course of the disease itself and concomitant abnormalities are described. Data on the toxicity of the drug and its safe use in pregnancy and lactation are also discussed

  14. Effect of membrane filtration of antimalarial drug solutions on in vitro activity against Plasmodium falciparum*

    OpenAIRE

    Baird, J K; Lambros, C.

    1984-01-01

    Antimalarial activities of chloroquine, mefloquine, amodiaquine, and quinine in vitro against Plasmodium falciparum were diminished as a consequence of membrane filtration. Filtered drug solutions gave ID50 values up to 25-fold greater than those of non-filtered (ethanol-sterilized) drug solutions. Loss of activity by filtration was overcome by increasing the drug concentration prior to filtration. Water solutions filtered through Millex-GS filter units consistently showed an absorbance maxim...

  15. Altered plasmodial surface anion channel activity and in vitro resistance to permeating antimalarial compounds

    OpenAIRE

    Lisk, Godfrey; Pain, Margaret; Sellers, Morgan; Gurnev, Philip A.; Pillai, Ajay D.; Bezrukov, Sergey M.; Desai, Sanjay A.

    2010-01-01

    Erythrocytes infected with malaria parasites have increased permeability to various solutes. These changes may be mediated by an unusual small conductance ion channel known as the plasmodial surface anion channel (PSAC). While channel activity benefits the parasite by permitting nutrient acquisition, it can also be detrimental because water-soluble antimalarials may more readily access their parasite targets via this channel. Recently, two such toxins, blasticidin S and leupeptin, were used t...

  16. Molecular surveillance of antimalarial drug resistance related genes in Plasmodium falciparum isolates from Eritrea.

    Science.gov (United States)

    Menegon, Michela; Nurahmed, Abduselam M; Talha, Albadawi A; Nour, Bakri Y M; Severini, Carlo

    2016-05-01

    The introduction of artemisinin-based combination therapy has led to extraordinary results in malaria control, however the recent emergence of partial resistance to artemisinin therapy in Southeast Asia jeopardizes these successes. This study aimed at investigating resistance to the antimalarial drugs by evaluating the polymorphisms in the PfK13, Pfcrt and Pfmdr1 genes in Plasmodium falciparum isolates obtained from patients in Eritrea.

  17. Serine Proteases of Malaria Parasite Plasmodium falciparum: Potential as Antimalarial Drug Targets

    OpenAIRE

    Asrar Alam

    2014-01-01

    Malaria is a major global parasitic disease and a cause of enormous mortality and morbidity. Widespread drug resistance against currently available antimalarials warrants the identification of novel drug targets and development of new drugs. Malarial proteases are a group of molecules that serve as potential drug targets because of their essentiality for parasite life cycle stages and feasibility of designing specific inhibitors against them. Proteases belonging to various mechanistic classes...

  18. Hallazgos complementarios sobre la actividad antimalarica del azul de metileno = Complementary findings on the antimalarial activity and toxicity of methylene blue

    OpenAIRE

    G. Garavito; Bertani, S; Deharo, Eric

    2008-01-01

    Methylene blue was reported as the first synthetic antimalarial by Ehrlich in 1881. It is currently no longer used for that purpose but it should be reconsidered since new economic alternatives are urgently needed in the arsenal of antimalarial drugs. The antimalarial activity of methylene blue is investigated here in vivo against rodent malaria parasites. 15 mg/kg daily dose of methylene blue inhibits 50% of the erythrocytic parasite growth of Plasmodium berghei and R yoelii nigeriensis, whi...

  19. Natural polyhydroxyalkanoate–gold nanocomposite based biosensor for detection of antimalarial drug artemisinin

    International Nuclear Information System (INIS)

    The worrisome trend of antimalarial resistance has already highlighted the importance of artemisinin as a potent antimalarial agent. The current investigation aimed at fabricating a biosensor based on natural polymer polyhydroxyalkanoate–gold nanoparticle composite mounting on an indium-tin oxide glass plate for the analysis of artemisinin. The biosensor was fabricated using an adsorbing horse-radish peroxidase enzyme on the electrode surface for which cyclic voltammetry was used to monitor the electro-catalytic reduction of artemisinin under diffusion controlled conditions. Electrochemical interfacial properties and immobilization of enzyme onto a polyhydroxyalkanoate–gold nanoparticle film were evaluated, and confirmed by cyclic voltammetry, electrochemical impedance spectroscopy and scanning electron microscopy. The differential pulse voltammetric peak current for artemisinin was increased linearly (concentration range of 0.01–0.08 μg mL−1) with sensitivity of 0.26 μA μg mL−1. The greater sensitivity of the fabricated biosensor to artemisinin (optimum limits of detection were 0.0035 μg mL−1 and 0.0036 μg mL−1 in bulk and spiked human serum, respectively) could be of much aid in medical diagnosis. - Highlights: • Extraction of PHA from indigenously isolated Pseudomonas aeruginosa BPC2 • Developed PHA/AuNPs/HRP/ITO based biosensor without the use of chemical cross linker • Detection of antimalarial drug artemisinin using the nanocomposite based biosensor

  20. Metabolic Dysregulation Induced in Plasmodium falciparum by Dihydroartemisinin and Other Front-Line Antimalarial Drugs.

    Science.gov (United States)

    Cobbold, Simon A; Chua, Hwa H; Nijagal, Brunda; Creek, Darren J; Ralph, Stuart A; McConville, Malcolm J

    2016-01-15

    Detailed information on the mode of action of antimalarial drugs can be used to improve existing drugs, identify new drug targets, and understand the basis of drug resistance. In this study we describe the use of a time-resolved, mass spectrometry (MS)-based metabolite profiling approach to map the metabolic perturbations induced by a panel of clinical antimalarial drugs and inhibitors on Plasmodium falciparum asexual blood stages. Drug-induced changes in metabolite levels in P. falciparum-infected erythrocytes were monitored over time using gas chromatography-MS and liquid chromatography-MS and changes in specific metabolic fluxes confirmed by nonstationary [(13)C]-glucose labeling. Dihydroartemisinin (DHA) was found to disrupt hemoglobin catabolism within 1 hour of exposure, resulting in a transient decrease in hemoglobin-derived peptides. Unexpectedly, it also disrupted pyrimidine biosynthesis, resulting in increased [(13)C]-glucose flux toward malate production, potentially explaining the susceptibility of P. falciparum to DHA during early blood-stage development. Unique metabolic signatures were also found for atovaquone, chloroquine, proguanil, cycloguanil and methylene blue. We also show that this approach can be used to identify the mode of action of novel antimalarials, such as the compound Torin 2, which inhibits hemoglobin catabolism. PMID:26150544

  1. Pyrazoleamide compounds are potent antimalarials that target Na+ homeostasis in intraerythrocytic Plasmodium falciparum.

    Science.gov (United States)

    Vaidya, Akhil B; Morrisey, Joanne M; Zhang, Zhongsheng; Das, Sudipta; Daly, Thomas M; Otto, Thomas D; Spillman, Natalie J; Wyvratt, Matthew; Siegl, Peter; Marfurt, Jutta; Wirjanata, Grennady; Sebayang, Boni F; Price, Ric N; Chatterjee, Arnab; Nagle, Advait; Stasiak, Marcin; Charman, Susan A; Angulo-Barturen, Iñigo; Ferrer, Santiago; Belén Jiménez-Díaz, María; Martínez, María Santos; Gamo, Francisco Javier; Avery, Vicky M; Ruecker, Andrea; Delves, Michael; Kirk, Kiaran; Berriman, Matthew; Kortagere, Sandhya; Burrows, Jeremy; Fan, Erkang; Bergman, Lawrence W

    2014-01-01

    The quest for new antimalarial drugs, especially those with novel modes of action, is essential in the face of emerging drug-resistant parasites. Here we describe a new chemical class of molecules, pyrazoleamides, with potent activity against human malaria parasites and showing remarkably rapid parasite clearance in an in vivo model. Investigations involving pyrazoleamide-resistant parasites, whole-genome sequencing and gene transfers reveal that mutations in two proteins, a calcium-dependent protein kinase (PfCDPK5) and a P-type cation-ATPase (PfATP4), are necessary to impart full resistance to these compounds. A pyrazoleamide compound causes a rapid disruption of Na(+) regulation in blood-stage Plasmodium falciparum parasites. Similar effect on Na(+) homeostasis was recently reported for spiroindolones, which are antimalarials of a chemical class quite distinct from pyrazoleamides. Our results reveal that disruption of Na(+) homeostasis in malaria parasites is a promising mode of antimalarial action mediated by at least two distinct chemical classes. PMID:25422853

  2. In-vitro antimalarial activity of azithromycin against chloroquine sensitive and chloroquine resistant Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Biswas S

    2001-10-01

    Full Text Available BAKGROUND: The spread of drug resistance in Plasmodium falciparum has made the situation essential to look into new effective therapeutic agents like antibiotics. Azithromycin is a potential, chemotherapeutic agent which possesses antimalarial activity and favourable pharmacokinetic properties. It is an azalide microbiocide derived semi-synthetically from macrolide erythromycin. Like other antibiotics, the azalide azithromycin has ability to inhibit protein synthesis on 70S ribosomes. SETTINGS: Experimental study. SUBJECTS AND METHODS: The parasiticidal profile was studied in five chloroquine sensitive and five chloroquine resistant P. falciparum isolates obtained from various places of India. The antimalarial activity was evaluated in P. falciparum schizont maturation by short term culture for 24 hours and by exposing the parasites to the drug for 96 hours. Parasites synchronized at ring stage were put for culture with various concentrations of azithromycin dihydrate (0.01-40 micro/ml. RESULTS: At highest concentration (40 micro/ml, parasite growth was inhibited totally in all 10 isolates. Antimalarial activity at 96 hours was greater than at 24 hours in both chloroquine sensitive and resistant parasites, which may indicate that the inhibition of parasite growth may occur at clinically achievable concentration of the drug when parasites were exposed for several asexual cycles. CONCLUSION: Azithromycin shows a potential for eventual use alone or in combination in the treatment of chloroquine sensitive and resistant P. falciparum malaria.

  3. The contribution of microscopy to targeting antimalarial treatment in a low transmission area of Tanzania

    Directory of Open Access Journals (Sweden)

    Mwerinde Ombeni

    2006-01-01

    Full Text Available Abstract Background There is a need for improved targeting of antimalarial treatment if artemisinin combination therapy is to be successfully introduced in Africa. This study aimed to explore why malaria slides are requested and how their results guide treatment decisions in an area of low transmission of P. falciparum. Methods Outpatients attending a district hospital in a highland area of Tanzania were studied over a 3-week period. Clinical and social data were collected from patients who had been prescribed an antimalarial or sent for a malaria slide. Hospital slides were re-read later by research methods. Results Of 1,273 consultations 132(10% were treated presumptively for malaria and 214(17% were sent for a malaria slide; only 13(6% of these were reported positive for P. falciparum but 96(48% of the 201 slide-negative cases were treated for malaria anyway. In a logistic regression model, adults (OR 3.86, P Conclusion Progress in targeting of antimalarials in low malaria transmission settings is likely to depend on consistent use of malaria microscopy and on the willingness of health workers to be guided by negative slide results. Further studies are needed to identify how this can be achieved.

  4. Natural and Semi synthetic Antimalarial Compounds: Emphasis on the Terpene Class.

    Science.gov (United States)

    Silva, G N S; Rezende, L C D; Emery, F S; Gosmann, G; Gnoatto, S C B

    2015-01-01

    Malaria is one of the most important tropical diseases since more than 40% of the world population is at risk. This disease is endemic to more than 100 nations and remains one of the main leading causes of death in children less than five years of age worldwide. Natural product-derived compounds have played a major role in drug discovery, often as prototypes to obtain more active semi synthetic derivatives. Antimalarial pharmacotherapy is a significant example of plant-derived medicines, such as quinine and artemisinin. This review highlights studies on terpenes and their semi synthetic derivatives from natural sources with antimalarial activity reported in the literature during eleven years (2002-2013). A total of 114 compounds are found among terpenes and their semi synthetic derivatives. Cytotoxicity of the compounds is also found in this review. Furthermore, the physicochemical properties of the terpenes addressed are discussed based on seven well established descriptors, which provide a useful source for the elaboration of a terpene library of antimalarial compounds. PMID:25553426

  5. Natural polyhydroxyalkanoate–gold nanocomposite based biosensor for detection of antimalarial drug artemisinin

    Energy Technology Data Exchange (ETDEWEB)

    Phukon, Pinkee [Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur 784028, Assam (India); Radhapyari, Keisham [Analytical Chemistry Division, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam (India); Konwar, Bolin Kumar [Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur 784028, Assam (India); Nagaland University (Central), Lumami, Zunheboto, Nagaland 798627 (India); Khan, Raju, E-mail: khan.raju@gmail.com [Analytical Chemistry Division, CSIR-North East Institute of Science and Technology, Jorhat 785006, Assam (India)

    2014-04-01

    The worrisome trend of antimalarial resistance has already highlighted the importance of artemisinin as a potent antimalarial agent. The current investigation aimed at fabricating a biosensor based on natural polymer polyhydroxyalkanoate–gold nanoparticle composite mounting on an indium-tin oxide glass plate for the analysis of artemisinin. The biosensor was fabricated using an adsorbing horse-radish peroxidase enzyme on the electrode surface for which cyclic voltammetry was used to monitor the electro-catalytic reduction of artemisinin under diffusion controlled conditions. Electrochemical interfacial properties and immobilization of enzyme onto a polyhydroxyalkanoate–gold nanoparticle film were evaluated, and confirmed by cyclic voltammetry, electrochemical impedance spectroscopy and scanning electron microscopy. The differential pulse voltammetric peak current for artemisinin was increased linearly (concentration range of 0.01–0.08 μg mL{sup −1}) with sensitivity of 0.26 μA μg mL{sup −1}. The greater sensitivity of the fabricated biosensor to artemisinin (optimum limits of detection were 0.0035 μg mL{sup −1} and 0.0036 μg mL{sup −1} in bulk and spiked human serum, respectively) could be of much aid in medical diagnosis. - Highlights: • Extraction of PHA from indigenously isolated Pseudomonas aeruginosa BPC2 • Developed PHA/AuNPs/HRP/ITO based biosensor without the use of chemical cross linker • Detection of antimalarial drug artemisinin using the nanocomposite based biosensor.

  6. A better resolution for integrating methods for monitoring Plasmodium falciparum resistance to antimalarial drugs.

    Science.gov (United States)

    Abdul-Ghani, Rashad; Al-Maktari, Mohamed T; Al-Shibani, Latifa A; Allam, Amal F

    2014-09-01

    Effective chemotherapy is the mainstay of malaria control. However, resistance of falciparum malaria to antimalarial drugs compromised the efforts to eliminate the disease and led to the resurgence of malaria epidemics. Three main approaches are used to monitor antimalarial drug efficacy and drug resistance; namely, in vivo trials, in vitro/ex vivo assays and molecular markers of drug resistance. Each approach has its implications of use as well as its advantages and drawbacks. Therefore, there is a need to use an integrated approach that would give the utmost effect to detect resistance as early as its emergence and to track it once spread. Such integration becomes increasingly needed in the era of artemisinin-based combination therapy as a forward action to deter resistance. The existence of regional and global networks for the standardization of methodology, provision of high quality reagents for the assessment of antimalarial drug resistance and dissemination of open-access data would help in approaching an integrated resistance surveillance system on a global scale.

  7. Methanol Improves Methane Uptake in Starved Methanotrophic Microorganisms

    OpenAIRE

    Jensen, Sigmund; Priemé, Anders; Bakken, Lars

    1998-01-01

    Methanotrophs in enrichment cultures grew and sustained atmospheric methane oxidation when supplied with methanol. If they were not supplied with methanol or formate, their atmospheric methane oxidation came to a halt, but it was restored within hours in response to methanol or formate. Indigenous forest soil methanotrophs were also dependent on a supply of methanol upon reduced methane access but only when exposed to a methane-free atmosphere. Their immediate response to each methanol additi...

  8. Synthesis and anti-cancer activity of 1,4-disubstituted imidazo[4,5-c]quinolines.

    Science.gov (United States)

    Thigulla, Yadagiri; Akula, Mahesh; Trivedi, Prakruti; Ghosh, Balaram; Jha, Mukund; Bhattacharya, Anupam

    2016-01-21

    The synthesis and anti-cancer activity evaluation of fused imidazoquinoline compounds is reported in this paper. Yb(OTf)3 has been utilized as a catalyst for the synthesis of 1,4-diaryl substituted imidazo[4,5-c]quinolines via a modified Pictet-Spengler approach. The desired imidazole ring was synthesized from imines using TosMIC (toluenesulfonylmethyl isocyanide) and subsequently functionalized at the C-4 position yielding an imidazoquinoline skeleton. Importantly, the final step was carried out without the aid of any prefunctionalization to obtain the resultant compounds in good yields. The synthesized compounds, when screened for anti-cancer activity, revealed the highest activity with 4-(2-bromophenyl)-1-phenyl-1H-imidazo[4,5-c]quinoline (IC50: 103.3 μM). PMID:26592542

  9. A Novel and Facile Synthesis of 2-(Benzofuran-2-yl)benzo[h]- quinoline-3-carboxylic Acid Derivatives

    Institute of Scientific and Technical Information of China (English)

    高文涛; 姜云; 李阳; 李凤; 闫岩

    2012-01-01

    A simple and concise approach for the synthesis of a series of new heterocyclic systems of 2-(benzofuran-2-yl)- benzo[h]quinoline-3-carboxylic acid derivatives (3a--3g) is described. The synthetic strategy features the one-pot reaction of ethyl 2-(chloromethyl)benzo[h]quinoline-3-carboxylate (2) with various substituted salicylaldehydes as well as 2-hydroxy-l-naphthaldehyde as a key step. The substrate 2 was prepared in good yield by a mild, efficient and direct reaction of 1-naphthylamine (1) with Vilsmeier-Haack reagent. The structures of all the new compounds were identified by spectral data and elemental analysis.

  10. CsxH3-xPW12O40 heteropoly salts catalyzed quinoline synthesis via Friedlander reaction

    Institute of Scientific and Technical Information of China (English)

    Ezzat Rafiee; Fereshte Khajooei Nejad; Mohammad Joshaghani

    2011-01-01

    Various type of cesium partially substituted phosphotungstate, CsxH3-xPW12O40 (x = 1.0, 2.0 and 2.5), were synthesized and their catalytic activities were investigated in the synthesis of quinoline. It was shown that catalytic activities of these catalysts correlated to surface acidity and total number of acidic sites. Finally, a series of quinoline derivatives were synthesized with Cs2.5H0.5PW12O40 via the Friedlander reaction in high to excellent yields and the plausible mechanism was proposed. Simple experiment, catalyst reusability, short reaction time and preclusion of toxic solvent are the advantages of this method.

  11. Discovery of Novel 3-Quinoline Carboxamides as Potent, Selective, and Orally Bioavailable Inhibitors of Ataxia Telangiectasia Mutated (ATM) Kinase.

    Science.gov (United States)

    Degorce, Sébastien L; Barlaam, Bernard; Cadogan, Elaine; Dishington, Allan; Ducray, Richard; Glossop, Steven C; Hassall, Lorraine A; Lach, Franck; Lau, Alan; McGuire, Thomas M; Nowak, Thorsten; Ouvry, Gilles; Pike, Kurt G; Thomason, Andrew G

    2016-07-14

    A novel series of 3-quinoline carboxamides has been discovered and optimized as selective inhibitors of the ataxia telangiectasia mutated (ATM) kinase. From a modestly potent HTS hit (4), we identified molecules such as 6-[6-(methoxymethyl)-3-pyridinyl]-4-{[(1R)-1-(tetrahydro-2H-pyran-4-yl)ethyl]amino}-3-quinolinecarboxamide (72) and 7-fluoro-6-[6-(methoxymethyl)pyridin-3-yl]-4-{[(1S)-1-(1-methyl-1H-pyrazol-3-yl)ethyl]amino}quinoline-3-carboxamide (74) as potent and highly selective ATM inhibitors with overall ADME properties suitable for oral administration. 72 and 74 constitute excellent oral tools to probe ATM inhibition in vivo. Efficacy in combination with the DSB-inducing agent irinotecan was observed in a disease relevant model. PMID:27259031

  12. Proficient Procedure for Preparation of Quinoline Derivatives Catalyzed by NbCl5 in Glycerol as Green Solvent

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Nasseri

    2015-01-01

    Full Text Available Quinolines, an important class of potentially bioactive compounds, have been synthesized by treatment of o-aminoaryl ketones and carbonyl compound utilizing niobium (V chloride (NbCl5 as an available and inexpensive catalyst. The quinoline derivatives were prepared in glycerol, an excellent solvent in terms of environmental impact, with high yields (76–98% and short reaction times (20–90 min. Not only diketones but also ketones afforded the desired products in good to excellent yields. The reaction time of 2-amino-5-chlorobenzophenone and dicarbonyl compounds was longer than that of 2-aminobenzophenone. The reaction of cyclic diketones took place faster than open chain analogues. These reactions also proceeded with acetophenone derivatives. In these cases the reaction times are longer.

  13. Synthesis of spiro[benzo[ℎ]quinoline-7,3'- indolines] via a three-component condensation reaction

    Indian Academy of Sciences (India)

    Abbas Rahmati; Miranda Eskandari-Vashareh

    2014-01-01

    An efficient one-pot synthesis of a new series of spiro[benzo[ℎ]quinoline-7,3'-indoline] was accomplished simply by the reaction of an isatin, naphthalen-1-amine and a CH-acid (,-dimethylbarbituric acid, barbituric acid, dimedone or 1,3-indandion) in acetic acid. During this process, the effects of solvent and temperature have been investigated on the yield of reactions.

  14. Quantum mechanical and astrophysical studies of methanol

    Directory of Open Access Journals (Sweden)

    Pineau des Forêts G.

    2012-10-01

    Full Text Available Interstellar methanol has been observed extensively at radio frequencies from the ground, and, very recently, it has been observed at higher frequencies, by means of the Herschel satellite. Being a complex molecule, methanol has a rich spectrum exhibiting rotational and internal torsional motions. However, by the same token, the determination of the cross sections and rate coefficients for the excitation of methanol by the principal perturbers, helium and molecular hydrogen, is a far from trivial task. We have recently extended and considerably improved previous calculations of these data. In the case of molecular hydrogen, results are now available for the excitation of both A- and E-type methanol, not only by para- but also by ortho-H2. These data have been used to model the HIFI observations of the outflow source L1157 B1. The methanol emission is computed self-consistently, in parallel with the dynamics and the chemistry, allowing for the optical depths in the emission lines by means of the LVG approximation. The results of these calculations are summarized.

  15. Methanol exchange between grassland and the atmosphere

    Directory of Open Access Journals (Sweden)

    A. Brunner

    2007-01-01

    Full Text Available Concentrations and fluxes of methanol were measured above two differently managed grassland fields (intensive and extensive in central Switzerland during summer 2004. The measurements were performed with a proton-transfer-reaction mass-spectrometer and fluxes were determined by the eddy covariance method. The observed methanol emission showed a distinct diurnal cycle and was strongly correlated with global radiation and water vapour flux. Mean and maximum daily emissions were found to depend on grassland species composition and, for the intensive field, also on the growing state. The extensive field with a more complex species composition had higher emissions than the graminoid-dominated intensive field, both on an area and on a biomass basis. A simple parameterisation depending on the water vapour flux and the leaf area index allowed a satisfying simulation of the temporal variation of methanol emissions over the growing phase. Accumulated carbon losses due to methanol emissions accounted for 0.024 and 0.048% of net primary productivity for the intensive and extensive field, respectively. The integral methanol emissions over the growing periods were more than one order of magnitude higher than the emissions related to cut and drying events.

  16. Opportunities for coal to methanol conversion

    Energy Technology Data Exchange (ETDEWEB)

    1980-04-01

    The accumulations of mining residues in the anthracite coal regions of Pennsylvania offer a unique opportunity to convert the coal content into methanol that could be utilized in that area as an alternative to gasoline or to extend the supplies through blending. Additional demand may develop through the requirements of public utility gas turbines located in that region. The cost to run this refuse through coal preparation plants may result in a clean coal at about $17.00 per ton. After gasification and synthesis in a 5000 ton per day facility, a cost of methanol of approximately $3.84 per million Btu is obtained using utility financing. If the coal is to be brought in by truck or rail from a distance of approximately 60 miles, the cost of methanol would range between $4.64 and $5.50 per million Btu depending upon the mode of transportation. The distribution costs to move the methanol from the synthesis plant to the pump could add, at a minimum, $2.36 per million Btu to the cost. In total, the delivered cost at the pump for methanol produced from coal mining wastes could range between $6.20 and $7.86 per million Btu.

  17. [Bis(quinolin-2-ylcarbonylamido-κ3N,N′,N′′]bromido(N,N-dimethylformamide-κOcopper(II

    Directory of Open Access Journals (Sweden)

    Md. Serajul Haque Faizi

    2014-06-01

    Full Text Available In the mononuclear title complex, [CuBr(C20H12N3O2(C3H7NO], synthesized from the quinoline-derived reduced Schiff base 4-(quinolin-2-ylmethylaminophenol, the coordination geometry around Cu2+ is distorted square-pyramidal, comprising a bromide anion at the apex [Cu—Br = 2.4671 (5 Å]. The base of the pyramid is built up from one dimethylformamide O-atom donor [Cu—O = 2.078 (2 Å] and three N-atom donors from the monoanionic, tridentate bis(quinolin-2-ylcarbonyldiimide ligand [Cu—Ndiimide = 1.941 (3 Å, and Cu—Nquinolyl = 2.060 (3 and 2.049 (3 Å]. An intramolecular C—H...O occurs. In the crystal, weak methyl and aromatic C—H...Br and formyl C—H...Ocarbonyl hydrogen-bonding interactions generate an overall layered structure lying parallel to (001.

  18. Synthesis and anticonvulsant activity of 7-benzylamino-4, 5-dihydro- [ 1, 2, 4] triazolo[ 4, 3-a] quinolines

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A series of 7-substituted-benzylamino-4, 5-dihydro-[ 1,2, 4]triazolo[4, 3-a] quinoline derivatives was synthesized and evaluated for their anticonvulsant activity. The subcutaneous pentylenetetrazole test (sc-PTZ) demonstrated that the most effective compound in controlling the sc-PTZ induced seizure was 7-(3-bromine-benzylamino)-4, 5-dihydro-[ 1,2, 4]triazolo[4, 3-a]quinoline (4j) with an ED50 of 5.0 mg/kg and the PI of 20.7, which was also safer than the reference drugs. And the maximal electroshock test (MES)demonstrated that among these derivatives, 7-(3-fluorobenzylamino) -4, 5-dihydro-[ 1,2, 4]trizolo[4, 3-a]quinoline (4i), with an ED50 of 15.3 mg/kg and the PI of 7.2, was the safest in MES test. Furthermore, their neurotoxicities were measured by the rotarod neurotoxicity test, and the results showed that all derivatives possessed lower neurotoxicity.

  19. Efficient green methanol synthesis from glycerol

    Science.gov (United States)

    Haider, Muhammad H.; Dummer, Nicholas F.; Knight, David W.; Jenkins, Robert L.; Howard, Mark; Moulijn, Jacob; Taylor, Stuart H.; Hutchings, Graham J.

    2015-12-01

    The production of biodiesel from the transesterification of plant-derived triglycerides with methanol has been commercialized extensively. Impure glycerol is obtained as a by-product at roughly one-tenth the mass of the biodiesel. Utilization of this crude glycerol is important in improving the viability of the overall process. Here we show that crude glycerol can be reacted with water over very simple basic or redox oxide catalysts to produce methanol in high yields, together with other useful chemicals, in a one-step low-pressure process. Our discovery opens up the possibility of recycling the crude glycerol produced during biodiesel manufacture. Furthermore, we show that molecules containing at least two hydroxyl groups can be converted into methanol, which demonstrates some aspects of the generality of this new chemistry.

  20. Photocatalytic conversion of methane to methanol

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, C.E.; Noceti, R.P.; D`Este, J.R. [Pittsburgh Energy Technology Center, PA (United States)

    1995-12-31

    A long-term goal of our research group is the exploration of novel pathways for the direct oxidation of methane to liquid fuels, chemicals, and intermediates. The use of three relatively abundant and inexpensive reactants, light, water, and methane, to produce methanol is attractive. The products of reaction, methanol and hydrogen, are both commercially desirable, methanol being used as is or converted to a variety of other chemicals, and the hydrogen could be utilized in petroleum and/or chemical manufacturing. Methane is produced as a by-product of coal gasification. Depending upon reactor design and operating conditions, up to 18% of total gasifier product may be methane. In addition, there are vast proven reserves of geologic methane in the world. Unfortunately, a large fraction of these reserves are in regions where there is little local demand for methane and it is not economically feasible to transport it to a market. There is a global research effort under way in academia, industry, and government to find methods to convert methane to useful, more readily transportable and storable materials. Methanol, the initial product of methane oxidation, is a desirable product of conversion because it retains much of the original energy of the methane while satisfying transportation and storage requirements. Investigation of direct conversion of methane to transportation fuels has been an ongoing effort at PETC for over 10 years. One of the current areas of research is the conversion of methane to methanol, under mild conditions, using light, water, and a semiconductor photocatalyst. The use of three relatively abundant and inexpensive reactants, light, water, and methane, to produce methanol, is attractive. Research in the laboratory is directed toward applying the techniques developed for the photocatalytic splitting of the water and the photochemical conversion of methane.

  1. Abacavir methanol 2.5-solvate

    Directory of Open Access Journals (Sweden)

    Phuong-Truc T. Pham

    2009-08-01

    Full Text Available The structure of abacavir (systematic name: {(1S,4R-4-[2-amino-6-(cyclopropylamino-9H-purin-9-yl]cyclopent-2-en-1-yl}methanol, C14H18N6O·2.5CH3OH, consists of hydrogen-bonded ribbons which are further held together by additional hydrogen bonds involving the hydroxyl group and two N atoms on an adjacent purine. The asymmetric unit also contains 2.5 molecules of methanol solvate which were grossly disordered and were excluded using SQUEEZE subroutine in PLATON [Spek, (2009. Acta Cryst. D65, 148–155].

  2. Abacavir methanol 2.5-solvate

    OpenAIRE

    Pham, Phuong-Truc T

    2009-01-01

    The structure of abacavir (systematic name: {(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl}methanol), C14H18N6O·2.5CH3OH, consists of hydrogen-bonded ribbons which are further held together by additional hydrogen bonds involving the hydroxyl group and two N atoms on an adjacent purine. The asymmetric unit also contains 2.5 molecules of methanol solvate which were grossly disordered and were excluded using SQUEEZE subroutine in PLATON [Spek, (2009...

  3. Environmental controls over methanol emission from leaves

    Directory of Open Access Journals (Sweden)

    P. Harley

    2007-12-01

    Full Text Available Methanol is found throughout the troposphere, with average concentrations second only to methane among atmospheric hydrocarbons. Proposed global methanol budgets are highly uncertain, but all agree that at least 60% of the total source arises from the terrestrial biosphere and primary emissions from plants. However, the magnitude of these emissions is also highly uncertain, and the environmental factors which control them require further elucidation.

    Using a temperature-controlled leaf enclosure, we measured methanol emissions from leaves of six plant species by proton transfer reaction mass spectrometry, with simultaneous measurements of leaf evapotranspiration and stomatal conductance. Rates of emission at 30°C varied from 0.2 to 38 μg g (dry mass−1 h−1, with higher rates measured on young leaves, consistent with the production of methanol via pectin demethylation in expanding foliage. On average, emissions increased by a factor of 2.3 for each 10°C increase in leaf temperature. At constant temperature, emissions were also correlated with co-varying incident photosynthetic photon flux density and rates of stomatal conductance. The data were analyzed using the emission model developed by Niinemets and Reichstein (2003a, b, with the incorporation of a methanol production term that increased exponentially with temperature. It was concluded that control of emissions, during daytime, was shared by leaf temperature and stomatal conductance, although rates of production may also vary diurnally in response to variations in leaf growth rate in expanding leaves. The model, which generally provided reasonable simulations of the measured data during the day, significantly overestimated emissions on two sets of measurements made through the night, suggesting that production rates of methanol were reduced at night, perhaps because leaf growth was reduced or possibly through a direct effect of light on production

  4. Environmental controls over methanol emission from leaves

    Directory of Open Access Journals (Sweden)

    P. Harley

    2007-08-01

    Full Text Available Methanol is found throughout the troposphere, with average concentrations second only to methane among atmospheric hydrocarbons. Proposed global methanol budgets are highly uncertain, but all agree that at least 60% of the total source arises from the terrestrial biosphere and primary emissions from plants. However, the magnitude of these emissions is also highly uncertain, and the environmental factors which control them require further elucidation.

    Using a temperature-controlled leaf enclosure, we measured methanol emissions from leaves of six plant species by proton transfer reaction mass spectrometry, with simultaneous measurements of leaf evapotranspiration and stomatal conductance. Rates of emission at 30°C varied from 0.3 to 38 μg g (dry mass−1 h−1, with higher rates measured on young leaves, consistent with the production of methanol via pectin demethylation in expanding foliage. On average, emissions increased by a factor of 2.4 for each 10°C increase in leaf temperature. At constant temperature, emissions were also correlated with co-varying incident photosynthetic photon flux density and rates of stomatal conductance. The data were analyzed using the emission model developed by Niinemets and Reichstein (2003a, b, with the incorporation of a methanol production term that increased exponentially with temperature. It was concluded that control of emissions, during daytime, was shared by leaf temperature and stomatal conductance, although rates of production may also vary diurnally in response to variations in leaf growth rate in expanding leaves. The model, which generally provided reasonable simulations of the measured data during the day, significantly overestimated emissions on two sets of measurements made through the night, suggesting that production rates of methanol were reduced at night, perhaps because leaf growth was reduced or possibly through a direct effect of light on production

  5. 37 GHz Methanol Masers : Horsemen of the Apocalypse for the Class II Methanol Maser Phase?

    Science.gov (United States)

    Ellingsen, S. P.; Breen, S. L.; Sobolev, A. M.; Voronkov, M. A.; Caswell, J. L.; Lo, N.

    2011-12-01

    We report the results of a search for class II methanol masers at 37.7, 38.3, and 38.5 GHz toward a sample of 70 high-mass star formation regions. We primarily searched toward regions known to show emission either from the 107 GHz class II methanol maser transition, or from the 6.035 GHz excited OH transition. We detected maser emission from 13 sources in the 37.7 GHz transition, eight of these being new detections. We detected maser emission from three sources in the 38 GHz transitions, one of which is a new detection. We find that 37.7 GHz methanol masers are only associated with the most luminous 6.7 and 12.2 GHz methanol maser sources, which in turn are hypothesized to be the oldest class II methanol sources. We suggest that the 37.7 GHz methanol masers are associated with a brief evolutionary phase (of 1000-4000 years) prior to the cessation of class II methanol maser activity in the associated high-mass star formation region.

  6. 37 GHz METHANOL MASERS : HORSEMEN OF THE APOCALYPSE FOR THE CLASS II METHANOL MASER PHASE?

    Energy Technology Data Exchange (ETDEWEB)

    Ellingsen, S. P.; Breen, S. L. [School of Mathematics and Physics, University of Tasmania, Private Bag 37, Hobart, TAS 7001 (Australia); Sobolev, A. M. [Astronomical Observatory, Ural Federal University, Lenin avenue 51, 620000 Ekaterinburg (Russian Federation); Voronkov, M. A.; Caswell, J. L. [CSIRO Astronomy and Space Science, Australia Telescope National Facility, P.O. Box 76, Epping, NSW 1710 (Australia); Lo, N., E-mail: Simon.Ellingsen@utas.edu.au [Departamento de Astronomia, Universidad de Chile, Camino El Observatorio 1515, Las Condes, Santiago, Casilla 36-D (Chile)

    2011-12-01

    We report the results of a search for class II methanol masers at 37.7, 38.3, and 38.5 GHz toward a sample of 70 high-mass star formation regions. We primarily searched toward regions known to show emission either from the 107 GHz class II methanol maser transition, or from the 6.035 GHz excited OH transition. We detected maser emission from 13 sources in the 37.7 GHz transition, eight of these being new detections. We detected maser emission from three sources in the 38 GHz transitions, one of which is a new detection. We find that 37.7 GHz methanol masers are only associated with the most luminous 6.7 and 12.2 GHz methanol maser sources, which in turn are hypothesized to be the oldest class II methanol sources. We suggest that the 37.7 GHz methanol masers are associated with a brief evolutionary phase (of 1000-4000 years) prior to the cessation of class II methanol maser activity in the associated high-mass star formation region.

  7. 37 GHz METHANOL MASERS : HORSEMEN OF THE APOCALYPSE FOR THE CLASS II METHANOL MASER PHASE?

    International Nuclear Information System (INIS)

    We report the results of a search for class II methanol masers at 37.7, 38.3, and 38.5 GHz toward a sample of 70 high-mass star formation regions. We primarily searched toward regions known to show emission either from the 107 GHz class II methanol maser transition, or from the 6.035 GHz excited OH transition. We detected maser emission from 13 sources in the 37.7 GHz transition, eight of these being new detections. We detected maser emission from three sources in the 38 GHz transitions, one of which is a new detection. We find that 37.7 GHz methanol masers are only associated with the most luminous 6.7 and 12.2 GHz methanol maser sources, which in turn are hypothesized to be the oldest class II methanol sources. We suggest that the 37.7 GHz methanol masers are associated with a brief evolutionary phase (of 1000-4000 years) prior to the cessation of class II methanol maser activity in the associated high-mass star formation region.

  8. 37 GHz methanol masers : Horsemen of the Apocalypse for the class II methanol maser phase?

    CERN Document Server

    Ellingsen, S P; Sobolev, A M; Voronkov, M A; Caswell, J L; Lo, N

    2011-01-01

    We report the results of a search for class II methanol masers at 37.7, 38.3 and 38.5 GHz towards a sample of 70 high-mass star formation regions. We primarily searched towards regions known to show emission either from the 107 GHz class II methanol maser transition, or from the 6.035 GHz excited OH transition. We detected maser emission from 13 sources in the 37.7 GHz transition, eight of these being new detections. We detected maser emission from three sources in the 38 GHz transitions, one of which is a new detection. We find that 37.7 GHz methanol masers are only associated with the most luminous 6.7 and 12.2 GHz methanol maser sources, which in turn are hypothesised to be the oldest class II methanol sources. We suggest that the 37.7 GHz methanol masers are associated with a brief evolutionary phase (of 1000-4000 years) prior to the cessation of class II methanol maser activity in the associated high-mass star formation region.

  9. The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Pierozan, Paula; Ferreira, Fernanda; Ortiz de Lima, Bárbara; Gonçalves Fernandes, Carolina [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003 (Brazil); Totarelli Monteforte, Priscila; Castro Medaglia, Natalia de; Bincoletto, Claudia; Soubhi Smaili, Soraya [Departamento de Farmacologia, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, SP (Brazil); Pessoa-Pureur, Regina, E-mail: rpureur@ufrgs.br [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003 (Brazil)

    2014-04-01

    Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24 h incubation with 100 µM QUIN, cells were exposed to {sup 32}P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca{sup 2+}/calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 μM), KN93 (10 μM) and staurosporin (10 nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca{sup 2+} quelators (1 mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca{sup 2+} influx through voltage-dependent Ca{sup 2+} channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24 h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative

  10. The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid

    International Nuclear Information System (INIS)

    Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24 h incubation with 100 µM QUIN, cells were exposed to 32P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca2+/calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 μM), KN93 (10 μM) and staurosporin (10 nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca2+ quelators (1 mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca2+ influx through voltage-dependent Ca2+ channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24 h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative disorders. - Highlights:

  11. A review of age-old antimalarial drug to combat malaria:efficacy upgradation by nanotechnology based drug delivery

    Institute of Scientific and Technical Information of China (English)

    Satyajit; Tripathy; Somenath; Roy

    2014-01-01

    Malaria is uncontrolled burden in the world till now.Despite of different efforts to develop antimalarial drug for decades,any anti-malarial drug can able to eradicate completely till now.Many anti-malarial substances are practically ineffectual because of their physicochemical limitations,cytotoxicity,chemical instability and degradation,and limited activities against intracellular parasites.Taking into consideration,the amount of research is going to conduct in the field of nanoparticle based drug delivery systems,lead to new ways of improving the treatment of infectious diseases.The study has focused on the progress and advancement of research on nanotechnology based drug delivery to eradicate the malaria.We like to focus the efficacy of nanotechnology based drug application for the opening out of novel chemotherapeutics in laboratory research,which may show the way to better use with age-old antimalarial drug and may draw the attention of pharmaceutical industries for the improvement and designing of effective anti-malarial drugs in future.

  12. Identification and deconvolution of cross-resistance signals from antimalarial compounds using multidrug-resistant Plasmodium falciparum strains.

    Science.gov (United States)

    Chugh, Monika; Scheurer, Christian; Sax, Sibylle; Bilsland, Elizabeth; van Schalkwyk, Donelly A; Wicht, Kathryn J; Hofmann, Natalie; Sharma, Anil; Bashyam, Sridevi; Singh, Shivendra; Oliver, Stephen G; Egan, Timothy J; Malhotra, Pawan; Sutherland, Colin J; Beck, Hans-Peter; Wittlin, Sergio; Spangenberg, Thomas; Ding, Xavier C

    2015-02-01

    Plasmodium falciparum, the most deadly agent of malaria, displays a wide variety of resistance mechanisms in the field. The ability of antimalarial compounds in development to overcome these must therefore be carefully evaluated to ensure uncompromised activity against real-life parasites. We report here on the selection and phenotypic as well as genotypic characterization of a panel of sensitive and multidrug-resistant P. falciparum strains that can be used to optimally identify and deconvolute the cross-resistance signals from an extended panel of investigational antimalarials. As a case study, the effectiveness of the selected panel of strains was demonstrated using the 1,2,4-oxadiazole series, a newly identified antimalarial series of compounds with in vitro activity against P. falciparum at nanomolar concentrations. This series of compounds was to be found inactive against several multidrug-resistant strains, and the deconvolution of this signal implicated pfcrt, the genetic determinant of chloroquine resistance. Targeted mode-of-action studies further suggested that this new chemical series might act as falcipain 2 inhibitors, substantiating the suggestion that these compounds have a site of action similar to that of chloroquine but a distinct mode of action. New antimalarials must overcome existing resistance and, ideally, prevent its de novo appearance. The panel of strains reported here, which includes recently collected as well as standard laboratory-adapted field isolates, is able to efficiently detect and precisely characterize cross-resistance and, as such, can contribute to the faster development of new, effective antimalarial drugs.

  13. METHANOL REMOVAL FROM METHANOL-WATER MIXTURE USING ACTIVATED SLUDGE, AIR STRIPPING AND ADSORPTION PROCESS: COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    SALAM K. AL-DAWERY

    2015-12-01

    Full Text Available An experimental research has been carried out in order to examine the removal of methanol from methanol-water mixtures using three different methods; activated sludge; activated carbon and air stripping. The results showed that the methanol was totally consumed by the bacteria as quickly as the feed entered the activated sludge vessel. Air stripping process has a limited ability for removing of methanol due to strong intermolecular forces between methanol and water; however, the results showed that the percentage of methanol removed using air pressure at 0.5 bar was higher than that of using air pressure of 0.25 bar. Removal of methanol from the mixture with a methanol content of 5% using activated carbon was not successful due to the limited capacity of the of the activated carbon. Thus, the activated sludge process can be considered as the most suitable process for the treatment of methanol-water mixtures.

  14. Direct applications of stabilized methanol from the liquid phase methanol (LPMEOH) process

    Energy Technology Data Exchange (ETDEWEB)

    Bhatt, B.L.; Heydorn, E.C.; Tijm, P.J.A.; Kornosky, R.M.

    1999-07-01

    The Liquid Phase Methanol (LPMEOH) process uses a slurry bubble column reactor to convert synthesis (syngas) gas to methanol. Because of its superior heat management, the process can directly utilize the carbon monoxide (CO)-rich syngas characteristic of the gasification of coal, petroleum coke, residual oil, wastes, or other hydrocarbon feedstocks. When added to an integrated gasification combined cycle (IGCC) power plant for peak shaving, the LPMEOH process converts a portion of the CO-rich syngas produced by the gasifier to methanol, and the unconverted gas is used to fuel the gas turbine combined-cycle power plant. A 260 short tons per day LPMEOH Process Demonstration Plant has been in operation at Eastman Chemical Company's chemicals-from-coal complex in Kingsport, Tennessee since April 1997. One of the advantages of the LPMEOH Process for coproduction of electric power and methanol from coal-derived syngas is that the as-produced, stabilized (degassed) methanol product is of unusually high quality (e.g. less than 1 wt% water) which may be suitable for direct use premium fuel applications. When compared to conventional methanol synthesis processes, cost savings of $0.04 to $0.11 per gallon of methanol can be achieved in coproduction facilities. However, the suitability of the stabilized product as a fuel must be demonstrated. A product-use test program has been developed to enhance the early commercial acceptance of central clean coal technology processing facilities, coproducing electricity and methanol. The objective of this program is to demonstrate commercial market applications for the ``as produced'' or stabilized methanol as a replacement fuel and as a fuel supplement. Fuel economics will be evaluated for the ``as produced'' methanol for use in municipal, industrial, and utility applications and as fuel supplements for gasoline, diesel, and natural gas. The applications (for example, as a hydrogen source for fuel cells, and as a

  15. Role of retinal metabolism in methanol-induced retinal toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Garner, C.D. [General Motors Corp., Warren, MI (United States)]|[Wayne State Univ., Detroit, MI (United States); Lee, E.W.; Terzo, T.S. [General Motors Corp., Warren, MI (United States); Louis-Ferdinand, R.T. [Wayne State Univ., Detroit, MI (United States)

    1995-08-01

    Methanol is a toxicant that causes systemic and ocular toxicity after acute exposure. The folate-reduced (FR) rat is an excellent animal model that mimics characteristic human methanol toxic responses. The present study examines the role of the methanol metabolites formaldehyde and formate in the initiation of methanol-induced retinal toxicity. After a single oral dose of 3.0 g/kg methanol, blood methanol concentrations were not significantly different in FR rats compared with folate-sufficient (FS) (control) rats. However, FR rats treated with 3.0 g/kg methanol displayed elevated blood (14.6 mM) and vitreous humor (19.5 mM) formate levels and abnormal electroretinograms (loss of b-wave) 48 h postdose. FR rats pretreated with disulfiram (DSF) prior to 3.0 g/kg methanol treatment failed to display these symptoms. Formaldehyde was not detected in blood or vitreous humor with or without DSF treatment, suggesting that formate is the toxic metabolite in methanol-induced retinal toxicity. Additionally, creating a blood formate profile (14.2 mM at 48 h) similar to that observed in methanol-treated rats by iv infusion of pH-buffered formate does not alter the electroretinogram as is observed with methanol treatment. These data suggest that intraretinal metabolism of methanol is necessary for the formate-mediated initiation of methanol-induced retinal toxicity. 31 refs., 5 figs., 2 tabs.

  16. Engineering Escherichia coli for methanol conversion

    NARCIS (Netherlands)

    Müller, Jonas E N; Meyer, Fabian; Litsanov, Boris; Kiefer, Patrick; Potthoff, Eva; Heux, Stéphanie; Quax, Wim J; Wendisch, Volker F; Brautaset, Trygve; Portais, Jean-Charles; Vorholt, Julia A

    2015-01-01

    Methylotrophic bacteria utilize methanol and other reduced one-carbon compounds as their sole source of carbon and energy. For this purpose, these bacteria evolved a number of specialized enzymes and pathways. Here, we used a synthetic biology approach to select and introduce a set of "methylotrophy

  17. Approach to the Treatment of Methanol Intoxication.

    Science.gov (United States)

    Kraut, Jeffrey A

    2016-07-01

    Methanol intoxication is an uncommon but serious poisoning. Its adverse effects are due primarily to the impact of its major metabolite formic acid and lactic acid resulting from cellular hypoxia. Symptoms including abdominal pain and loss of vision can appear a few hours to a few days after exposure, reflecting the time necessary for accumulation of the toxic byproducts. In addition to a history of exposure, increases in serum osmolal and anion gaps can be clues to its presence. However, increments in both parameters can be absent depending on the nature of the toxic alcohol, time of exposure, and coingestion of ethanol. Definitive diagnosis requires measurement with gas or liquid chromatography, which are laborious and expensive procedures. Tests under study to detect methanol or its metabolite formate might facilitate the diagnosis of this poisoning. Treatment can include administration of ethanol or fomepizole, both inhibitors of the enzyme alcohol dehydrogenase to prevent formation of its metabolites, and hemodialysis to remove methanol and formate. In this Acid-Base and Electrolyte Teaching Case, a patient with methanol intoxication due to ingestion of model airplane fuel is described, and the value and limitations of current and new diagnostic and treatment measures are discussed. PMID:27180631

  18. Parameters affecting methanol utilization by yeasts

    Energy Technology Data Exchange (ETDEWEB)

    Foda, M.S.; El-Masry, H.G.

    1981-01-01

    Screening of 28 yeast cultures, representing 22 species of various yeasts, with respect to their capabilities to assimilate methanol, has shown that this property was mostly found in certain species of the two genera Hansenula and Candida. When methanol was used as a sole carbon source for a methanol-adapted strain of Hansenula polymorpha, a linear yield response could be obtained with increasing alcohol up to 2% concentration. The amount of inoculum proved to be the decisive factor in determining a priori the ability of the organism to grow at 6% methanol as final concentration. The optimum pH values for growth ranged between 4.5-5.5 with no growth at pH 6.5 or higher. A marked growth stimulation was obtained when the medium was supplied with phosphate up to 0.08 M as final concentration. Within the nitrogen sources tested, corn steep liquor concentrate gave the highest yield of cells. The significance of the obtained results are discussed with reference to feasibilities of application.

  19. HYDROGEN BONDING IN THE METHANOL DIMER

    Science.gov (United States)

    In this work, two methanol molecules are placed in different arrangements to study hydrogen bonding in carbohydrate materials such as cellulose. Energy was calculated as a function of both hydrogen bond length and angle over wide ranges, using quantum mechanics (QM). The QM wavefunctions are analyze...

  20. Synthesis and Optimization of a Methanol Proces

    DEFF Research Database (Denmark)

    Grue, J.; Bendtsen, Jan Dimon

    2003-01-01

    In the present paper, a simulation model for a methanol process is proposed. The objective is to develop a model for flowsheet optimization, which requires simple thermodynamic and unit operation models. Simplified thermodynamic models are combined with a more advanced model for the rate of...

  1. Synthesis and Optimization of a Methanol Process

    DEFF Research Database (Denmark)

    Grue, J.; Bendtsen, Jan Dimon

    2003-01-01

    In the present paper, a simulation model for a methanol process is proposed. The objective is to develop a model for flowsheet optimization, which requires simple thermodynamic and unit operation models. Simplified thermodynamic models are combined with a more advanced model for the rate of...

  2. Optimized fuel cell grade hydrogen from methanol

    Science.gov (United States)

    Choi, Yongtaek

    2003-10-01

    To evaluate reaction rates liar making hydrogen from methanol, kinetic studies of methanol decomposition, methanol steam reforming, water gas shift reaction, and CO selective oxidation have been performed. These reactions were studied in a micro reactor testing unit using a commercial Cu-ZnO/Al2O3 catalyst for the first three reactions and Pt-Fe/gamma-alumina catalyst for the last reaction. The activity tests were performed between 120˜325°C and atmospheric pressure with a range of feed rates and compositions. For methanol decomposition, water addition to the feed increased the yield of hydrogen and reduced the formation of by-products. XPS analysis of used catalyst samples and time on-stream data showed that the Cu2+ oxidation state of copper favors methanol decomposition. A simplified reaction network of 5 elementary reactions was proposed and all five rate expressions were obtained using non-linear least squares optimization, numerical integration of a one-dimensional PFR model, and extensive experimental data. Similar numerical analysis was carried out to obtain the rate expressions for methanol steam reaction, the water gas shift reaction, and CO selective oxidation. For the kinetics of the water gas shift reaction, an empirical rate expression was obtained from the experimental data. Based on a review of published work on the WGS reaction mechanism, our study found that a rate expression derived from a regenerative mechanism and another rate expression derived from adsorptive mechanism fit the experimental data equally well. For the kinetics of CO preferential oxidation, a reaction model in which three reactions (CO oxidation, H2 oxidation and the WGS reaction) occur simultaneously was chosen to predict the reactor performance. In particular the reverse water gas shift reaction had an important role when fitting the experimental data precisely and explained the selectivity decrease at higher reaction temperatures. Combining the three reactors and several

  3. 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

  4. Effects of impregnation methods and drying conditions on quinoline hydrodenitrogenation over Ni-W based catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Fang; Qiu, Zegang; Zhao, Liangfu; Xiang, Hongwei [Institute of Coal Chemistry, Chinese Academy of Sciences (China); Guo, Shaoqing [Taiyuan University of Science and Technology (China)

    2014-04-15

    The effects of impregnation methods (co-impregnation and sequential impregnation) and drying conditions (air and vacuum) on the structure and catalytic behavior of MCM-41 supported Ni-W catalysts were investigated. The catalysts were characterized by powder X-ray diffraction (XRD) analysis, Fourier-transform infrared spectroscopy (FT-IR), diffuse reflectance UV-Vis absorbance spectroscopy (DRS), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and pyridine adsorbed infrared spectroscopy (Py-IR) techniques. They were tested for hydrodenitrogenation (HDN) of quinoline at temperatures of 300-400 deg C. The HDN results showed that the catalysts prepared by co-impregnation were more active than the catalysts prepared by sequential impregnation and the catalysts prepared by drying under vacuum were more active than the catalysts dried in air. Characterization revealed that the co-impregnation method and drying under vacuum promoted the dispersion of W, the formation of the active phases, and the formation of acidic sites on the catalysts. (author)

  5. Green synthesis of novel quinoline based imidazole derivatives and evaluation of their antimicrobial activity

    Directory of Open Access Journals (Sweden)

    N.C. Desai

    2014-12-01

    Full Text Available We have described the conventional and microwave method for the synthesis of N-(4-((2-chloroquinolin-3-ylmethylene-5-oxo-2-phenyl-4,5-dihydro-1H-imidazol-1-yl(arylamides 3a–l. It is observed that the solvent-free microwave thermolysis is a convenient, rapid, high-yielding, and environmental friendly protocol for the synthesis of quinoline based imidazole derivatives when compared with conventional reaction in a solution phase. Antimicrobial activity of the newly synthesized compounds is screened in vitro on the following microbial cultures: Escherichia coli (MTCC 443, Pseudomonas aeruginosa (MTCC 1688, Staphylococcus aureus (MTCC 96, Streptococcus pyogenes (MTCC 442, Candida albicans (MTCC 227, Aspergillus niger (MTCC 282, Aspergillus clavatus (MTCC 1323. All the synthesized bio-active molecules are tested for their in vitro antimicrobial activity by bioassay namely serial broth dilution. Among these compounds 3c, 3d, 3f, 3h and 3j show significant potency against different microbial strains. All the compounds have been characterized by IR, 1H NMR, 13C NMR and mass spectral data. On the basis of statistical analysis, it is observed that these compounds give significant co-relation.

  6. Establishment of true niacin deficiency in quinolinic acid phosphoribosyltransferase knockout mice.

    Science.gov (United States)

    Terakata, Miki; Fukuwatari, Tsutomu; Sano, Mitsue; Nakao, Natsuki; Sasaki, Ryuzo; Fukuoka, Shin-Ichi; Shibata, Katsumi

    2012-12-01

    Pyridine nucleotide coenzymes are involved in >500 enzyme reactions and are biosynthesized from the amino acid L-tryptophan (L-Trp) as well as the vitamin niacin. Hence, "true" niacin-deficient animals cannot be "created" using nutritional techniques. We wanted to establish a truly niacin-deficient model animal using a protocol that did not involve manipulating dietary L-Trp. We generated mice that are missing the quinolinic acid (QA) phosphoribosyltransferase (QPRT) gene. QPRT activity was not detected in qprt(-/-)mice. The qprt(+/+), qprt(+/-), or qprt(-/-) mice (8 wk old) were fed a complete diet containing 30 mg nicotinic acid (NiA) and 2.3 g L-Trp/kg diet or an NiA-free diet containing 2.3 g L-Trp/kg diet for 23 d. When qprt(-/-)mice were fed a complete diet, food intake and body weight gain did not differ from those of the qprt(+/+) and qprt(+/-) mice. On the contrary, in the qprt(-/-) mice fed the NiA-free diet, food intake and body weight were reduced to 60% (P niacin, such as blood and liver NAD concentrations, were also lower in the qprt(-/-) mice than in the qprt(+/+) and the qprt(+/-) mice. Urinary excretion of QA was greater in the qprt(-/-) mice than in the qprt(+/+) and qprt(+/-) mice (P niacin-deficient mice.

  7. Determination of three physical properties of quinoline ionic liquids with hexafluorophosphate

    Directory of Open Access Journals (Sweden)

    Tang Dan

    2016-01-01

    Full Text Available Densities of one acidic ionic liquid (IL Quinolinum hexafluorophosphate ([HBpy][PF6], and four neutral dicationic ionic liquids (ILs based on quinoline and hexafluoro-phosphate and linked with poly(ethylene glycol (PEG: ([PEG200-DIL][PF6]2, [PEG400-DIL][PF6]2, [PEG800-DIL][PF6]2 and [PEG1000-DIL][PF6]2 were determined. In addition, the solubilities of six ILs in six lower alcohols, water, acetonitrile and diethyl ether were measured at 288.15 K; and the hydroscopicity of above five ILs were measured at the temperature of 298.15 K and relative humidity of 79% for 24 h. Densities of five ionic liquids were determined between 283.15 and 333.15 K. Then the densities of five binary system (ILs/acetonitrile were explored between 283.15 and 333.15 K, the type of the ionic liquid, the concentration of five ILs in CH3CN, and the effect of temperature on the binary systems, were correlated with the measured data.

  8. Investigations into low pressure methanol synthesis

    Energy Technology Data Exchange (ETDEWEB)

    Sharafutdinov, I.

    2013-03-15

    The central topic of this work has been synthesis, characterization and optimization of novel Ni-Ga based catalysts for hydrogenation of CO{sub 2} to methanol. The overall goal was to search for materials that could be used as a low temperature (and low pressure) methanol synthesis catalyst. This is required for small scale delocalized methanol production sites, where installation of energy demanding compression units should be avoided. The work was triggered by DFT calculations, which showed that certain bimetallic systems are active towards methanol synthesis from CO{sub 2} and H{sub 2} at ambient pressure. Among them, Ni-Ga has been chosen, primarily due to low price of constituent metals. After the preliminary optimization work, an optimal catalyst composition and preparation method has been suggested. Indeed, for an optimal catalyst, which is a SiO{sub 2} supported Ni-Ga prepared from a solution of nitrates containing 5:3 molar ratio of Ni:Ga, the intrinsic activity (methanol production rate per active surface area) is comparable to that of highly optimised Cu/ZnO/Al{sub 2}O{sub 3}. Formation of the catalyst was investigated with the aid of in-situ XRD and in-situ XAS techniques. The mechanism of alloying was proposed. It was found that the Ni-Ga nanoparticle formation always proceeds through a more Ni-rich phase. These studies were backed up with the electron microscopy, x-ray fluorescence, thermogravimetric analysis and mass spectroscopy. The catalyst was found to deactivate both at normal reaction conditions (presumably due to carbon formation) and under accelerated ageing conditions (due to dealloying). However, the initial activity could always be restored after treatment in hydrogen flow at elevated temperatures. The work in the direction of suppression of deactivation and by-product formation is still in progress. (Author)

  9. In vitro and in vivo characterization of the antimalarial lead compound SSJ-183 in Plasmodium models

    Directory of Open Access Journals (Sweden)

    Schleiferböck S

    2013-11-01

    Full Text Available Sarah Schleiferböck,1,2 Christian Scheurer,1,2 Masataka Ihara,3,4 Isamu Itoh,3,4 Ian Bathurst,5,† Jeremy N Burrows,5 Pascal Fantauzzi,5 Julie Lotharius,5 Susan A Charman,6 Julia Morizzi,6 David M Shackleford,6 Karen L White,6 Reto Brun,1,2 Sergio Wittlin1,21Swiss Tropical and Public Health Institute, Basel, 2University of Basel, Basel, Switzerland; 3Drug Discovery Science Research Center, Hoshi University, Shinagawa, Tokyo, Japan; 4Synstar Japan Co, Ltd, Odawara, Japan; 5Medicines for Malaria Venture, Geneva, Switzerland; 6Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Parkville, VIC, Australia †Ian Bathurst passed away on 26 June 2011Abstract: The objective of this work was to characterize the in vitro (Plasmodium falciparum and in vivo (Plasmodium berghei activity profile of the recently discovered lead compound SSJ-183. The molecule showed in vitro a fast and strong inhibitory effect on growth of all P. falciparum blood stages, with a tendency to a more pronounced stage-specific action on ring forms at low concentrations. Furthermore, the compound appeared to be equally efficacious on drug-resistant and drug-sensitive parasite strains. In vivo, SSJ-183 showed a rapid onset of action, comparable to that seen for the antimalarial drug artesunate. SSJ-183 exhibited a half-life of about 10 hours and no significant differences in absorption or exposure between noninfected and infected mice. SSJ-183 appears to be a promising new lead compound with an attractive antimalarial profile.Keywords: antimalarial studies, cross-resistance, stage-specificity, Plasmodium falciparum

  10. Molecular Farming in Artemisia annua, a Promising Approach to Improve Anti-malarial Drug Production.

    Science.gov (United States)

    Pulice, Giuseppe; Pelaz, Soraya; Matías-Hernández, Luis

    2016-01-01

    Malaria is a parasite infection affecting millions of people worldwide. Even though progress has been made in prevention and treatment of the disease; an estimated 214 million cases of malaria occurred in 2015, resulting in 438,000 estimated deaths; most of them occurring in Africa among children under the age of five. This article aims to review the epidemiology, future risk factors and current treatments of malaria, with particular focus on the promising potential of molecular farming that uses metabolic engineering in plants as an effective anti-malarial solution. Malaria represents an example of how a health problem may, on one hand, influence the proper development of a country, due to its burden of the disease. On the other hand, it constitutes an opportunity for lucrative business of diverse stakeholders. In contrast, plant biofarming is proposed here as a sustainable, promising, alternative for the production, not only of natural herbal repellents for malaria prevention but also for the production of sustainable anti-malarial drugs, like artemisinin (AN), used for primary parasite infection treatments. AN, a sesquiterpene lactone, is a natural anti-malarial compound that can be found in Artemisia annua. However, the low concentration of AN in the plant makes this molecule relatively expensive and difficult to produce in order to meet the current worldwide demand of Artemisinin Combination Therapies (ACTs), especially for economically disadvantaged people in developing countries. The biosynthetic pathway of AN, a process that takes place only in glandular secretory trichomes of A. annua, is relatively well elucidated. Significant efforts have been made using plant genetic engineering to increase production of this compound. These include diverse genetic manipulation approaches, such as studies on diverse transcription factors which have been shown to regulate the AN genetic pathway and other biological processes. Results look promising; however, further

  11. A new antimalarial agent; effect of extracts of Artemisia diffusa against Plasmodium berghei

    Directory of Open Access Journals (Sweden)

    Abdolhossein Rustaiyan

    2009-01-01

    Full Text Available Malaria is one of the most serious health problems in many parts of the world, particularly in Africa and Latin America with a high mortality rate. The situation is further complicated by the spread of drug-resistant parasites in many parts where plasmodium falciparum is endemic. A few alternative drugs are under development, necessitating urgent efforts to identify new classes of antimalarial agents. There is therefore a need to find new, effective and affordable remedies for malaria, including those derived from plants. The clinical utility of the Chinese discovery of artemisinin from the herb Artemisia annua has stimulated much interest in traditional plants as potential sources of new antimalarial drugs. In this study, the antimalarial activity of Artemisia diffusa extracts and the fraction which contains sesquiterpene lactones including Tehranolide, on Plasmodium berghei in vivo on the mice model of malaria was investigated. We did our best to carry out the biological tests as well as the phytochemical investigations from the same collection. It demonstrates that crude extracts of Artemisia diffusa inhibit the growth of Plasmodium berghei in vivo in NMRI mice. The microscopic examination of Giemsa stained slides showed a virtual absence of all blood-stage of murine malaria treated with three concentrations of herbal extracts including 27, 2.7 and 0.27 mg/ml. These observations suggest that the active constituents in the extract may be cytotoxic for P. berghei, thereby inhibiting their development to the erythrocytic stage. The results specifically indicated the inhibitory effects of the A.diffusa crude extracts and the fraction which contains sesquiterpene lactones including Tehranolide, on the developmental stages of P. berghei by decreasing parasitaemia.

  12. Antimalarial activity of potential inhibitors of Plasmodium falciparum lactate dehydrogenase enzyme selected by docking studies.

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    Julia Penna-Coutinho

    Full Text Available The Plasmodium falciparum lactate dehydrogenase enzyme (PfLDH has been considered as a potential molecular target for antimalarials due to this parasite's dependence on glycolysis for energy production. Because the LDH enzymes found in P. vivax, P. malariae and P. ovale (pLDH all exhibit ∼90% identity to PfLDH, it would be desirable to have new anti-pLDH drugs, particularly ones that are effective against P. falciparum, the most virulent species of human malaria. Our present work used docking studies to select potential inhibitors of pLDH, which were then tested for antimalarial activity against P. falciparum in vitro and P. berghei malaria in mice. A virtual screening in DrugBank for analogs of NADH (an essential cofactor to pLDH and computational studies were undertaken, and the potential binding of the selected compounds to the PfLDH active site was analyzed using Molegro Virtual Docker software. Fifty compounds were selected based on their similarity to NADH. The compounds with the best binding energies (itraconazole, atorvastatin and posaconazole were tested against P. falciparum chloroquine-resistant blood parasites. All three compounds proved to be active in two immunoenzymatic assays performed in parallel using monoclonals specific to PfLDH or a histidine rich protein (HRP2. The IC(50 values for each drug in both tests were similar, were lowest for posaconazole (<5 µM and were 40- and 100-fold less active than chloroquine. The compounds reduced P. berghei parasitemia in treated mice, in comparison to untreated controls; itraconazole was the least active compound. The results of these activity trials confirmed that molecular docking studies are an important strategy for discovering new antimalarial drugs. This approach is more practical and less expensive than discovering novel compounds that require studies on human toxicology, since these compounds are already commercially available and thus approved for human use.

  13. Studies on laser flash photolysis and pulse radiolysis of quinoline and some of its derivatives%喹啉及其衍生物的脉冲辐解和激光光解研究

    Institute of Scientific and Technical Information of China (English)

    ZHU Dazhang; WANG Shilong; SUN Xiaoyu; LI Wenzhe; ZENG Kailing; NI Yaming; WANG Wenfeng; YAO Side

    2005-01-01

    Quinoline and some of its derivatives were reported to be carcinogenic, toxic and mutagenic[1-3]. The widespread use of quinoline and its derivatives entails that these compounds are distributed in the environment, polluting soil and water together with many other environmental chemicals.Time-resolved laser flash photolysis and pulse radiolysis have been used to study the reaction of quinoline (Q), 2, 6-dimethyl-quinoline (DMQ) and isoquinoline (IQ) with hydrated electrons, hydroxyl radicals and hydrogen radicals. Transient absorption spectra were obtained and reaction rate constants to the reactions were determined, as showed in Table 1. Rossible mechanisms of the reactions were suggested.In addition, oxidization reactions of SO4·-, Br2·- and N3·- with isoquinoline, quinoline and its derivatives were studied. It showed that SO4- could oxidize quinoline, 2, 6-dimethylquinoline and isoquinoline; Br2·-could oxidize isoquinoline to its cation radicals, but it could not oxidize quinoline or 2, 6-diemethylquinoline; N3·- could oxidize none of them.With a better understandings on photolysis and radiolysis of isoquinoline, quinoline and its derivates, the study is of help for degradation of the chemicals and for environment protection.

  14. Understanding private sector antimalarial distribution chains: a cross-sectional mixed methods study in six malaria-endemic countries.

    Directory of Open Access Journals (Sweden)

    Benjamin Palafox

    Full Text Available BACKGROUND: Private for-profit outlets are important treatment sources for malaria in most endemic countries. However, these outlets constitute only the last link in a chain of businesses that includes manufacturers, importers and wholesalers, all of which influence the availability, price and quality of antimalarials patients can access. We present evidence on the composition, characteristics and operation of these distribution chains and of the businesses that comprise them in six endemic countries (Benin, Cambodia, Democratic Republic of Congo, Nigeria, Uganda and Zambia. METHODS AND FINDINGS: We conducted nationally representative surveys of antimalarial wholesalers during 2009-2010 using an innovative sampling approach that captured registered and unregistered distribution channels, complemented by in-depth interviews with a range of stakeholders. Antimalarial distribution chains were pyramidal in shape, with antimalarials passing through a maximum of 4-6 steps between manufacturer and retailer; however, most likely pass through 2-3 steps. Less efficacious non-artemisinin therapies (e.g. chloroquine dominated weekly sales volumes among African wholesalers, while volumes for more efficacious artemisinin-based combination therapies (ACTs were many times smaller. ACT sales predominated only in Cambodia. In all countries, consumer demand was the principal consideration when selecting products to stock. Selling prices and reputation were key considerations regarding supplier choice. Business practices varied across countries, with large differences in the proportions of wholesalers offering credit and delivery services to customers, and the types of distribution models adopted by businesses. Regulatory compliance also varied across countries, particularly with respect to licensing. The proportion of wholesalers possessing any up-to-date licence from national regulators was lowest in Benin and Nigeria, where vendors in traditional markets are

  15. Understanding Private Sector Antimalarial Distribution Chains: A Cross-Sectional Mixed Methods Study in Six Malaria-Endemic Countries

    Science.gov (United States)

    Palafox, Benjamin; Patouillard, Edith; Tougher, Sarah; Goodman, Catherine; Hanson, Kara; Kleinschmidt, Immo; Rueda, Sergio Torres; Kiefer, Sabine; O’Connell, Kathryn A.; Zinsou, Cyprien; Phok, Sochea; Akulayi, Louis; Arogundade, Ekundayo; Buyungo, Peter; Mpasela, Felton; Chavasse, Desmond

    2014-01-01

    Background Private for-profit outlets are important treatment sources for malaria in most endemic countries. However, these outlets constitute only the last link in a chain of businesses that includes manufacturers, importers and wholesalers, all of which influence the availability, price and quality of antimalarials patients can access. We present evidence on the composition, characteristics and operation of these distribution chains and of the businesses that comprise them in six endemic countries (Benin, Cambodia, Democratic Republic of Congo, Nigeria, Uganda and Zambia). Methods and Findings We conducted nationally representative surveys of antimalarial wholesalers during 2009–2010 using an innovative sampling approach that captured registered and unregistered distribution channels, complemented by in-depth interviews with a range of stakeholders. Antimalarial distribution chains were pyramidal in shape, with antimalarials passing through a maximum of 4–6 steps between manufacturer and retailer; however, most likely pass through 2–3 steps. Less efficacious non-artemisinin therapies (e.g. chloroquine) dominated weekly sales volumes among African wholesalers, while volumes for more efficacious artemisinin-based combination therapies (ACTs) were many times smaller. ACT sales predominated only in Cambodia. In all countries, consumer demand was the principal consideration when selecting products to stock. Selling prices and reputation were key considerations regarding supplier choice. Business practices varied across countries, with large differences in the proportions of wholesalers offering credit and delivery services to customers, and the types of distribution models adopted by businesses. Regulatory compliance also varied across countries, particularly with respect to licensing. The proportion of wholesalers possessing any up-to-date licence from national regulators was lowest in Benin and Nigeria, where vendors in traditional markets are important

  16. Evaluation of the ex vivo antimalarial activity of organotin (IV) ethylphenyldithiocarbamate on erythrocytes infected with Plasmodium berghei NK 65.

    Science.gov (United States)

    Awang, Normah; Jumat, Hafizah; Ishak, Shafariatul Akmar; Kamaludin, Nurul Farahana

    2014-06-01

    Malaria is the most destructive and dangerous parasitic disease. The commonness of this disease is getting worse mainly due to the increasing resistance of Plasmodium falciparum against antimalarial drugs. Therefore, the search for new antimalarial drug is urgently needed. This study was carried out to evaluate the effects of dibutyltin (IV) ethylphenyldithiocarbamate (DBEP), diphenyltin (IV) ethylphenyldithiocarbamate (DPEP) and triphenyltin (IV) ethylphenyldithiocarbamate (TPEP) compounds as antimalarial agents. These compounds were evaluated against erythrocytes infected with Plasmodium berghei NK65 via ex vivo. Organotin (IV) ethylphenyldithiocarbamate, [R(n)Sn(C9H10NS2)(4-n)] with R = C4H9 and C6H5 for n = 2; R = C6H5 for n = 3 is chemically synthesised for its potential activities. pLDH assay was employed for determination of the concentration that inhibited 50% of the Plasmodium's activity (IC50) after 24 h treatment at concentration range of 10-0.0000001 mg mL(-1). Plasmodium berghei NK65 was cultured in vitro to determine the different morphology of trophozoite and schizont. Only DPEP and TPEP compounds have antimalarial activity towards P. berghei NK65 at IC50 0.094±0.011 and 0.892±0.088 mg mL(-1), respectively. The IC50 of DPEP and TPEP were lowest at 30% parasitemia with IC50 0.001±0.00009 and 0.0009±0.0001 mg mL(-1), respectively. In vitro culture showed that TPEP was effective towards P. berghei NK65 in trophozoite and schizont morphology with IC50 0.0001±0.00005 and 0.00009±0.00003 μg mL(-1), respectively. In conclusion, DPEP and TPEP have antimalarial effect on erythrocytes infected with P. berghei NK65 and have potential as antimalarial and schizonticidal agents. PMID:26035957

  17. Minimizing the Entropy Production of the Methanol Producing Reaction in a Methanol Reactor

    OpenAIRE

    Kjelstrup, Signe; Bedeaux, Dick; Johannessen, Eivind; Rosjorde, Audun; Nummedal, Lars

    2000-01-01

    The entropy production of the reaction that produces methanol in a methanol reactor, has been minimized. The results show that the entropy production of the reaction can be reduced by more than 70%. The optimal path through the reactor is characterized by a driving force for the chemical reaction that is close to constant. The entropy production due to heat transfer across the reactor walls in this state is large, however. Variations of the reactor design show that it is possible to accomplis...

  18. In vitro antimalarial drug susceptibility in Thai border areas from 1998–2003

    Directory of Open Access Journals (Sweden)

    Mungthin Mathirut

    2005-08-01

    Full Text Available Abstract Background The Thai-Myanmar and Thai-Cambodia borders have been historically linked with the emergence and spread of Plasmodium falciparum parasites resistant to antimalarial drugs. Indeed, the areas are often described as harbouring multi-drug resistant parasites. These areas of Thailand have experienced significant changes in antimalarial drug exposure patterns over the past decade. This study describes the in vitro antimalarial susceptibility patterns of 95 laboratory-adapted P. falciparum isolates, collected between 1998 and 2003,. Methods Ninety five P. falciparum isolates were collected from five sites in Thailand between 1998 and 2003. After laboratory adaptation to in vitro culture, the susceptibility of these parasites to a range of established antimalarial drugs (chloroquine [CQ], mefloquine [MQ], quinine [QN] and dihydroartemisinin [DHA] was determined by the isotopic microtest. Results Mefloquine (MQ sensitivity remained poorest in areas previously described as MQ-resistant areas. Sensitivity to MQ of parasites from this area was significantly lower than those from areas reported to harbour moderate (p = 0.002 of low level MQ resistance (p = 000001. Importantly for all drugs tested, there was a considerable range in absolute parasite sensitivities. There was a weak, but statistically positive correlation between parasite sensitivity to CQ and sensitivity to both QN and MQ and a positive correlation between MQ and QN. In terms of geographical distribution, parasites from the Thai-Cambodia were tended to be less sensitive to all drugs tested compared to the Thai-Myanmar border. Parasite sensitivity to all drugs was stable over the 6-year collection period with the exception of QN. Conclusion This study highlights the high degree of variability in parasite drug sensitivity in Thailand. There were geographical differences in the pattern of resistance which might reflect differences in drug usage in each area. In contrast to many

  19. Anti-malarial market and policy surveys in sub-Saharan Africa

    Directory of Open Access Journals (Sweden)

    Sevcsik Ann-Marie

    2010-04-01

    Full Text Available Abstract At a recent meeting (Sept 18, 2009 in which reasons for the limited access to artemisinin-based combination therapy (ACT in sub-Saharan Africa were discussed, policy and market surveys on anti-malarial drug availability and accessibility in Burundi and Sierra Leone were presented in a highly interactive brainstorming session among key stakeholders across private, public, and not-for-profit sectors. The surveys, the conduct of which directly involved the national malaria control programme managers of the two countries, provides the groundwork for evidence-based policy implementation. The results of the surveys could be extrapolated to other countries with similar socio-demographic and malaria profiles. The meeting resulted in recommendations on key actions to be taken at the global, national, and community level for better ACT accessibility. At the global level, both public and private sectors have actions to take to strengthen policies that lead to the replacement of loose blister packs with fixed-dose ACT products, develop strategies to ban inappropriate anti-malarials and regulate those bans, and facilitate technology and knowledge transfer to scale up production of fixed-dose ACT products, which should be readily available and affordable to those patients who are in the greatest need of these medicines. At the national level, policies that regulate the anti-malarial medicines market should be enacted and enforced. The public sector, including funding donors, should participate in ensuring that the private sector is engaged in the ACT implementation process. Research similar to the surveys discussed is important for other countries to develop and evaluate the right incentives at a local level. At the community level, community outreach and education about appropriate preventive and treatment measures must continue and be strengthened, with service delivery systems developed within both public and private sectors, among other measures

  20. Molecular Farming in Artemisia annua, a sustainable approach to improve anti-malarial drug production

    Directory of Open Access Journals (Sweden)

    Giuseppe ePulice

    2016-03-01

    Full Text Available Malaria is a parasite infection affecting millions of people worldwide. Even though progresses in prevention and treatment have been developed, 198 million cases of malaria occurred in 2013, resulting in 584000 estimated deaths. 90% of all malaria deaths occurred in Africa, mostly among children under the age of five. This article aims to review malaria’s history, epidemiology and current treatments, with a particular focus on the potential of molecular farming that use metabolic engineering in plants as effective anti-malarial solution. Malaria indeed represents an example of how a health problem on one hand, may eventually influence the proper development of a country due to the burden of the disease, and on the other hand, constitutes an opportunity for lucrative business of diverse stakeholders. In contrast, plant biofarming is here proposed as a sustainable alternative for the production not only of natural herbal repellents used for malaria prevention but also for the production of sustainable anti-malarial drugs like artemisinin used for primary parasite infection treatments.Artemisinin, a sesquiterpene lactone, is a natural anti-malarial compound that can be found in Artemisia annua plant. However, the low concentration of artemisinin in plant makes this molecule relatively expensive and difficult to meet the worldwide demand of Artemisinin Combination Therapies, especially for economically disadvantaged people in developing countries. The biosynthetic pathway of artemisinin, a process that only takes place in glandular secretory trichomes of A. annua, is relatively well elucidated, and significant efforts using plant genetic engineering have been made to increase the production of this compound. These include studies on diverse transcription factors, which all have been shown to regulate artemisinin genetic pathway and other biological processes. Therefore, genetic manipulation of these genes may be used as a cost-effective potential

  1. A new phloroglucinol derivative from Hypericum calycinum with antifungal and in vitro antimalarial activity.

    Science.gov (United States)

    Decosterd, L A; Hoffmann, E; Kyburz, R; Bray, D; Hostettmann, K

    1991-12-01

    The new phloroglucinol derivative 1 has been isolated from the light petroleum ether extract of the aerial parts of Hypericum calycinum. Its structure has been established by means of 1H- and 13C-NMR spectroscopy and by nOe, MHQC, and HMBC experiments on its monomethyl ether derivative 3. Compound 1 was fungicidal against Cladosporium cucumerinum in a TLC bioassay. In addition, this new phloroglucinol derivative was also found to exert an interesting antimalarial activity in an in vitro test system. PMID:1818346

  2. Characterization of PfTrxR inhibitors using antimalarial assays and in silico techniques

    OpenAIRE

    Munigunti, Ranjith; Gathiaka, Symon; Acevedo, Orlando; Sahu, Rajnish; Tekwani, Babu; Angela I. Calderón

    2013-01-01

    Background The compounds 1,4-napthoquinone (1,4-NQ), bis-(2,4-dinitrophenyl)sulfide (2,4-DNPS), 4-nitrobenzothiadiazole (4-NBT), 3-dimethylaminopropiophenone (3-DAP) and menadione (MD) were tested for antimalarial activity against both chloroquine (CQ)-sensitive (D6) and chloroquine (CQ)-resistant (W2) strains of Plasmodium falciparum through an in vitro assay and also for analysis of non-covalent interactions with P. falciparum thioredoxin reductase (PfTrxR) through in silico docking studies...

  3. Synthesis, antimalarial properties and 2D-QSAR studies of novel triazole-quinine conjugates.

    Science.gov (United States)

    Faidallah, Hassan M; Panda, Siva S; Serrano, Juan C; Girgis, Adel S; Khan, Khalid A; Alamry, Khalid A; Therathanakorn, Tanya; Meyers, Marvin J; Sverdrup, Francis M; Eickhoff, Christopher S; Getchell, Stephen G; Katritzky, Alan R

    2016-08-15

    Click chemistry technique led to novel 1,2,3-triazole-quinine conjugates 8a-g, 10a-o, 11a-h and 13 utilizing benzotriazole-mediated synthetic approach with excellent yields. Some of the synthesized analogs (11a, 11d-h) exhibited antimalarial properties against Plasmodium falciparum strain 3D7 with potency higher than that of quinine (standard reference used) through in vitro standard procedure bio-assay. Statistically significant BMLR-QSAR model describes the bio-properties, validates the observed biological observations and identifies the most important parameters governing bio-activity. PMID:27298002

  4. Compound antimalarial ethosomal cataplasm: preparation, evaluation, and mechanism of penetration enhancement

    OpenAIRE

    Shen S; Liu SZ; Zhang YS; Du MB; Liang AH; Song LH; Ye ZG

    2015-01-01

    Shuo Shen, Shu-Zhi Liu, Yu-Shi Zhang, Mao-Bo Du, Ai-Hua Liang, Li-Hua Song, Zu-Guang Ye Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, People’s Republic of China Abstract: Malaria is still a serious public health problem in some parts of the world. The problems of recurrence and drug resistance are increasingly more serious. Thus, it is necessary to develop a novel antimalarial agent. The objectives of this study were to construct a novel ...

  5. Quality of anti-malarials collected in the private and informal sectors in Guyana and Suriname

    Directory of Open Access Journals (Sweden)

    Evans Lawrence

    2012-06-01

    Full Text Available Abstract Background Despite a significant reduction in the number of malaria cases in Guyana and Suriname, this disease remains a major problem in the interior of both countries, especially in areas with gold mining and logging operations, where malaria is endemic. National malaria control programmes in these countries provide treatment to patients with medicines that are procured and distributed through regulated processes in the public sector. However, availability to medicines in licensed facilities (private sector and unlicensed facilities (informal sector is common, posing the risk of access to and use of non-recommended treatments and/or poor quality products. Methods To assess the quality of circulating anti-malarial medicines, samples were purchased in the private and informal sectors of Guyana and Suriname in 2009. The sampling sites were selected based on epidemiological data and/or distance from health facilities. Samples were analysed for identity, content, dissolution or disintegration, impurities, and uniformity of dosage units or weight variation according to manufacturer, pharmacopeial, or other validated method. Results Quality issues were observed in 45 of 77 (58% anti-malarial medicines sampled in Guyana of which 30 failed visual & physical inspection and 18 failed quality control tests. The proportion of monotherapy and ACT medicines failing quality control tests was 43% (13/30 and 11% (5/47 respectively. A higher proportion of medicines sampled from the private sector 34% (11/32 failed quality control tests versus 16% (7/45 in the informal sector. In Suriname, 58 medicines were sampled, of which 50 (86% were Artecom®, the fixed-dose combination of piperaquine-dihydroartemisinin-trimethoprim co-blistered with a primaquine phosphate tablet. All Artecom samples were found to lack a label claim for primaquine, thus failing visual and physical inspection. Conclusions The findings of the studies in both countries point to

  6. Saleability of anti-malarials in private drug shops in Muheza, Tanzania

    DEFF Research Database (Denmark)

    Ringsted, Frank M; Massawe, Isolide S; Lemnge, Martha M;

    2011-01-01

    Background: Artemether-lumefantrine (ALu) replaced sulphadoxine-pymimethamine (SP) as the official first-line anti-malarial in Tanzania in November 2006. So far, artemisinin combination therapy (ACT) is contra-indicated during pregnancy by the national malaria treatment guidelines, and pregnant...... women depend on SP for Intermittent Preventive Treatment (IPTp) during pregnancy. SP is still being dispensed by private drug stores, but it is unknown to which extent. If significant, it may undermine its official use for IPTp through induction of resistance. The main study objective was to perform...... of fever or malaria, and are important providers,...

  7. Antimalarial drug resistance of Plasmodium falciparum in India: changes over time and space

    OpenAIRE

    Shah, Naman K.; Dhillon, Gajender P S; Dash, Adtiya P; Arora, Usha; Meshnick, Steven R.; Valecha, Neena

    2011-01-01

    After the launch of the National Malaria Control Programme in 1953, the number of malaria cases reported in India fell to an all-time low of 0·1 million in 1965. However, the initial success could not be maintained and a resurgence of malaria began in the late 1960s. Resistance of Plasmodium falciparum to chloroquine was first reported in 1973 and increases in antimalarial resistance, along with rapid urbanisation and labour migration, complicated the challenge that India’s large geographical...

  8. Methanol production from Eucalyptus wood chips. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Fishkind, H.H.

    1982-06-01

    This feasibility study includes all phases of methanol production from seedling to delivery of finished methanol. The study examines: production of 55 million, high quality, Eucalyptus seedlings through tissue culture; establishment of a Eucalyptus energy plantation on approximately 70,000 acres; engineering for a 100 million gallon-per-day methanol production facility; potential environmental impacts of the whole project; safety and health aspects of producing and using methanol; and development of site specific cost estimates.

  9. In Vitro and In Vivo Antimalarial Activity of Ficus thonningii Blume (Moraceae and Lophira alata Banks (Ochnaceae, Identified from the Ethnomedicine of the Nigerian Middle Belt

    Directory of Open Access Journals (Sweden)

    M. O. Falade

    2014-01-01

    Full Text Available Drug resistance in Plasmodium falciparum requires that new drugs must be developed. Plants are a potential source for drug discovery and development. Two plants that used to treat febrile illnesses in Nigeria were tested for in vitro and in vivo antimalarial activity and cytotoxicity in cancer cell lines. Methanol, hexane, and ethyl acetate leaf extracts of Ficus thonningii and Lophira alata were active in in vitro assays against P. falciparum NF54 (sensitive and K1 (multiresistant strains. Hexane extracts of F. thonningii and L. alata were the most effective extracts in in vitro assays with IC50 of 2.7±1.6 μg/mL and 2.5±0.3 μg/mL for NF54 and 10.4±1.6 μg/mL and 2.5±2.1 μg/mL for K1 strain. All extracts were nontoxic in cytotoxicity assays against KB human cell line with IC50 of over 20 μg/mL, demonstrating selectivity against P. falciparum. In vivo analysis shows that hexane extracts of both plants reduced parasitaemia. At the maximum dose tested, L. alata had a 74.4% reduction of parasitaemia while F. thonningii had a reduction of 84.5%, both extracts prolonged animal survival in mice infected with P. berghei NK65 when compared with vehicle treated controls. The antiplasmodial activity observed justifies the use of both plants in treating febrile conditions.

  10. Prediction of potential antimalarial targets of artemisinin based on protein information from whole genome of Plasmodium falciparum

    Institute of Scientific and Technical Information of China (English)

    HAN LiPing; HUANG Qiang; NAN Peng; ZHONG Yang

    2009-01-01

    On the basis of the genomic data and protein pathway information about Plasmodium falciparum clone 3D7 from the NCBI taxonomy database and the KEGG database,eight key protein enzymes in the signal pathways were selected to perform molecular docking with artemisinin.The binding modes obtained from the molecular docking suggested that purine nucleoside phosphorylase (pfPNP),peptide deformylase (pfPDF),and ribose 5-phosphate isomerase (pfRpiA) may be involved in the antimalarial mode of action of artemisinin.Artemisinin exhibited its antimalarial activity probably by interfering with the metabolic pathways of purine,pyrimidine,methionine,glyoxylate and dicarboxylate,or pentose phosphate.

  11. Acidities of Water and Methanol in Aqueous Solution and DMSO

    Science.gov (United States)

    Gao, Daqing

    2009-01-01

    The relative acidities of water and methanol have been a nagging issue. In gas phase, methanol is more acidic than water by 36.0 kJ/mol; however, in aqueous solution, the acidities of methanol and water are almost identical. The acidity of an acid in solution is determined by both the intrinsic gas-phase ionization Gibbs energy and the solvent…

  12. Synthesis in aqueous medium and organic praseodymium complexes with ligands derived from Schiff base quinolinic. Characterization and physicochemical study; Sintesis en medio acuoso y organico de complejos de praseodimio con ligantes derivados de base de Schiff quinolicos. Caracterizacion y estudio fisicoquimico

    Energy Technology Data Exchange (ETDEWEB)

    Garcia G, A.

    2015-07-01

    It was investigated the coordination ability of the quinolinic Schiff base organic tetradentate quinolinic ligand (Q Schiff-(OH){sub 2}) towards the trivalent praseodymium by UV/Vis spectrophotometric titration (St). By St, was studied the formed species between the Q Schiff-(OH){sub 2} ligand and the praseodymium nitrate salt in equimolar concentrations (5.86 x 10{sup -4} M: 5.22 x 10{sup -4} M) in methanol. The statistical analysis of the experimental results suggested three complexed species with 1Pr:3L, 1Pr:2L y 1Pr:1L stoichiometries. The predominant stoichiometries were the second and the latter. Based on these results and data from the scientific literature, the methodology for the syntheses of the complexes Q Schiff-(OH){sub 2}-Pr in aqueous-organic and organic media was established and a molar ratio M:L= 1:2 of praseodymium nitrate and the ligand was used. The new complexes were characterized by UV/Vis, Infrared, X-ray Photoelectron Spectroscopy (XP S), Diffuse Reflectance (Dr) and Thermogravimetric Analysis/Differential Scanning Calorimetry (TGA/DSC). Elemental analysis of C, N, O and Pr by XP S suggested 1Pr:2L:1Na (PrC{sub 32}H{sub 20}N{sub 4}O{sub 4}Na) stoichiometry of the complex synthesized by the aqueous-organic medium while for the complex synthesized by the organic medium it was 1Pr:3L (PrC{sub 48}H{sub 33}N{sub 6}O{sub 6}). In the first case, the praseodymium ion charge was neutralized by the anionic ligands whose remaining charge was compensated by the sodium ion. In the second case, the ion charge was neutralized by the ligands. The minimum formula was Pr(Q Schiff){sub 2}Na for the pure coordination compound from the aqueous-organic medium and the minimum formula Pr(Q Schiff){sub 3} for that from the organic medium. XP S also indicated that the oxidation state of praseodymium ion was maintained. Both complexes were stable in methanol, ethanol and acetonitrile at least for 5 days. The photophysical properties of the studied complexes were

  13. 3-(2,3,5,6,7,8-Hexahydro-1H-cyclopenta[b]quinolin-9-yl-1,5-bis(4-methoxyphenylbiuret

    Directory of Open Access Journals (Sweden)

    Koichiro Nishibe

    2010-03-01

    Full Text Available Ipidacrine (2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinolin-9-amine was reacted with 4-methoxyphenyl isocyanate to give the title compound, C28H30N4O4. An intramolecular N—H...O hydrogen bond results in an essentially planar [r.m.s. deviation from the mean plane is 0.126 (1 Å] conformation for the biuret unit. The central ring of the quinoline unit is twisted by 78.2 (1° with respect to the biuret mean plane, whereas the two 4-methoxybenzene rings are twisted out of this plane by 24.3 (1° and 48.5 (1°, resulting in an overall propeller-like structure. An intermolecular N—H...N hydrogen bond between the biuret NH atom and the quinoline ring nitrogen defines the crystal packing.

  14. An efficient access to the synthesis of novel 12-phenylbenzo[6,7]oxepino[3,4-b]quinolin-13(6H-one derivatives

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    Wentao Gao

    2012-10-01

    Full Text Available An efficient access to the tetracyclic-fused quinoline systems, 12-phenylbenzo[6,7]oxepino[3,4-b]quinolin-13(6H-one derivatives 4a–l, is described, involving the intramolecular Friedel–Crafts acylation reaction of 2-(phenoxymethyl-4-phenylquinoline-3-carboxylic acid derivatives 3a–l aided by the treatment with PPA (polyphosphoric acid or Eaton’s reagent. The required starting compound (2 was obtained by Friedländer reaction of 2-aminobenzophenone (1 with 4-chloroethylacetoacetate by using CAN (cerium ammonium nitrate, 10 mol % as catalyst at room temperature. The substrates 3a–l were prepared through one-pot reaction of ethyl 2-(chloromethyl-4-phenylquinoline-3-carboxylate (2 and substituted phenols. Our developed strategy, involving a three-step route, offers easy access to tetracyclic-fused quinoline systems in short reaction times, and the products are obtained in moderate to good yields.

  15. Enhanced electrokinetic remediation of quinoline-contaminated soils%喹啉污染土壤的电动强化修复研究

    Institute of Scientific and Technical Information of China (English)

    任大军; 周思思; 刘剑; 张元元

    2012-01-01

    Kaolin was selected as a test soil and quinoline was investigated as a typical pollutant. The characteristic of migration and its effect of quinoline in Kaolin under different voltage gradient and experimental time were studied, revealing the mechanism of using electrokinetic technology to remediate the quinoline-contaminated in soils. The results show that the electrokinetic transport processes can effectively stimulate the desorption and movement of the quinoline in the test soils. Migration rate and distance of quinoline will increase along with the voltage gradient growth under some conditions. Electromigration and electroosmosis are the main mechanisms both driving the quinoline migrate toward the cathode.%以高岭土为实验土壤,喹啉为代表污染物,研究了不同电压梯度和运行时间下土壤中喹啉的迁移特征和效果,揭示了利用电动力学技术迁移土壤中喹啉的作用机理.结果表明:电动力学过程能有效地促进土壤中喹啉的解吸附和迁移,迁移速率和距离在一定条件下随电压强度升高而增大;电渗析和电迁移是其主要作用机理,均推动喹啉向阴极移动.

  16. SYNTHESIS AND CYTOTOXIC ACTIVITY OF NEW 5H-INDOLO[2,3-B]QUINOLINE O-AMINOGLYCOSIDES.

    Science.gov (United States)

    Badowska-Rosłonek, Katarzyna; Ciesielska, Agnieszka; Switalska, Marta; Piskozub, Małgorzata; Peczyńska-Czoch, Wanda; Wietrzyk, Joanna; Kaczmarek, Łukasz

    2016-01-01

    Novel 5H-indolo[2,3-b]quinoline O-aminoglycosides were synthesized in order to check the hypothesis that the construction of hybrids composed of the active 5H-indolo[2,3-b]quinoline chromophore and daunosaminyl or acosaminyl moiety may result in the cytotoxic activity of the obtained derivatives that is much higher than the one of the parent DIMIQ (5,11-dimethyl-5H-indolo[2,3-b]quinoline) and 6H-indoloquinoline analogs. Actually, 5H-indolo[2,3-b]indoloquinoline O-aminoglycosides showed the anti-proliferative activity in vitro against human lung adenocarcinoma A549, breast cancer MCF-7, melanoma Hs294T, promyelocytic leukemia HL-60, uterine sarcoma MES-SA and colon cancer LoVo cell lines, which was 10 times higher than that of the 6H-analogs and comparable to the one of the referential DIMIQ. Unexpectedly, it appeared that except for HL-60/MX2 (P-gp-independent and topoisomerase II-dependent resistance), other MDR tumor cell lines (LoVo/DX. P-gp-dependent, MRP-, LRP-dependent multidrug resistance) and MES-SA/DX5 (P-gp-dependent resistance to doxorubicin) are also resistant to the 5H-indolo[2,3-b]indoloquinoline O-aminoglycosides tested. This is surprising because 6H-analogs, in general, 10 times less active against non-MDR tumor cell lines, as well as the DIMIQ itself, are able to overcome drug resistance in all MDR cell lines examined. The cytotoxicity of the tested compounds against tumor cell lines and against normal cells (mice fibroblasts BALB/3T3) was comparable. PMID:27476287

  17. Antimalarial properties of Artemisia vulgaris L. ethanolic leaf extract in a Plasmodium berghei murine malaria model

    Directory of Open Access Journals (Sweden)

    Gayan S. Bamunuarachchi

    2013-12-01

    Full Text Available Background & objectives: Artemisinin isolated from Artemisia annua is the most potent antimalarial drug against chloroquine-resistant Plasmodium falciparum malaria. Artemisia vulgaris, an invasive weed, is the only Artemisia species available in Sri Lanka. A pilot study was undertaken to investigate the antiparasitic activity of an A. vulgaris ethanolic leaf extract (AVELE in a P. berghei ANKA murine malaria model that elicits pathogenesis similar to falciparum malaria. Methods: A 4-day suppressive and the curative assays determined the antiparasitic activity of AVELE using four doses (250, 500, 750 and 1000 mg/kg, Coartem® as the positive control and 5% ethanol as the negative control in male ICR mice infected with P. berghei. Results: The 500, 750 and 1000 mg/kg doses of AVELE significantly (p ≤0.01 inhibited parasitaemia by 79.3, 79.6 and 87.3% respectively, in the 4-day suppressive assay, but not in the curative assay. Chronic administration of the high dose of AVELE ruled out overt signs of toxicity and stress as well as hepatotoxicity, renotoxicity and haematotoxicity. Interpretation & conclusion: The oral administration of a crude ethonolic leaf extract of A. vulgaris is non-toxic and possesses potent antimalarial properties in terms of antiparasitic activity.

  18. An Alternative Paradigm for the Role of Antimalarial Plants in Africa

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    Steven Maranz

    2012-01-01

    Full Text Available Most investigations into the antimalarial activity of African plants are centered on finding an indigenous equivalent to artemisinin, the compound from which current frontline antimalarial drugs are synthesized. As a consequence, the standard practice in ethnopharmacological research is to use in vitro assays to identify compounds that inhibit parasites at nanomolar concentrations. This approach fails to take into consideration the high probability of acquisition of resistance to parasiticidal compounds since parasite populations are placed under direct selection for genetic that confers a survival advantage. Bearing in mind Africa's long exposure to malaria and extensive ethnobotanical experimentation with both therapies and diet, it is more likely that compounds not readily overcome by Plasmodium parasites would have been retained in the pharmacopeia and cuisine. Such compounds are characterized by acting primarily on the host rather than directly targeting the parasite and thus cannot be adequately explored in vitro. If Africa's long history with malaria has in fact produced effective plant therapies, their scientific elucidation will require a major emphasis on in vivo investigation.

  19. Virtual Screening and Docking Studies of Synthesized Chalcones: Potent Anti-Malarial Drug

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    Prashant Singh

    2016-03-01

    Full Text Available A novel series of Chalcones were synthesized targets asexual blood stages of Plasmodium falciparum has been analyzed by utilizing a combination of molecular modeling techniques. Statistically significant structure-based quantitative structure activity relationships models were generated and validated through acceptable predictive ability to support internal and external set of compounds. Screening of most valuable drug among of pre-synthesized drug on the basis of binding efficiency to target receptor was carried out by docking view. Prior this pre-computed Mean IC50 and MIC value were also taken in consideration. The most effective compound on the basis all consideration was found. Previous studies have suggested that Ca2+-ATPase (PfATP6 of P. falciparum is the target of many anti-malarial drugs. However, the mechanism of inhibition of Ca2+- ATPase (PfATP6 is not known. Here we address this issue using bioinformatics tools. We generated a molecular model of Ca2+-ATPase (PfATP6 of P. falciparum and performed molecular docking of all chalcones. Molecular docking programme Glide iGEMDock was used to determine binding feasibility of 52 analogues of chalcones. The comparison of docking parameters showed, more than 5 analogues are better ligands of PfATP6. The binding of chalocones to PFATP6 is mediated by both hydrogen bonding, hydrophobic and polar interactions. Our results suggest that chalcones analogues are promising lead compounds for the development of anti-malarial drugs

  20. Phytochemical screening, antimalarial and histopathological studies of Allophylus africanus and Tragia benthamii

    Institute of Scientific and Technical Information of China (English)

    Oladosu I.A.; Balogun S.O.; Ademowo G.O.

    2013-01-01

    The anti-malarial potential of different parts ofAllophylus africanus P.Beauv and Tragia benthamii Baker were determined in vivo for suppressive,curative and cytotoxic activities in mice receiving 0.2 mL of a standard inoculum size of 1 × 107 infected erythrocytes of Plasmodium berghei (NK-65) intraperitoneally.The A.africanus extracts suppressed parasitaemia following administration to infected mice by 92.82%-97.81% on day 7 post-infection against 96.81% for chloroquine.The infected extract-treated animals had significantly moderate (P < 0.05) packed cell volume (PCV) compared with the infected,untreated animals.Phytochemical screening revealed a predominance of tannins,saponins,flavonoids and carbohydrates in all parts of A.africanus,and alkaloids instead of flavonoids in the extract of T.benthamii.The results suggest that the extract possesses considerable antimalarial activity.These results support further studies on A.africanus.

  1. In vitro and in vivo anti-malarial activity of Boerhavia elegans and Solanum surattense

    Directory of Open Access Journals (Sweden)

    Khodakarim Nastaran

    2010-05-01

    Full Text Available Abstract Background There is an urgent need to identify new anti-malarial drug targets for both prophylaxis and chemotherapy, due to the increasing problem of drug resistance to malaria parasites. In the present study, the aim was to discover novel, effective plant-based extracts for the activity against malaria. Methods Ten plants found in Iran were selected by ethnobotanical survey of medicinal plants. The crude ethanolic extracts were tested for in vitro anti-plasmodial activity against two strains of Plasmodium falciparum: K1 (chloroquine-resistant strain and CY27 (chloroquine-sensitive strain, using the parasite lactate dehydrogenase (pLDH assay. The anti-plasmodial activity of the extracts was also assessed in the 4-day suppressive anti-malarial assay in mice inoculated with Plasmodium berghei (ANKA strain. Crude ethanolic extracts showed good anti-plasmodial activity were further fractionated by partitioning in water and dichloromethane. Results Of 10 plant species assayed, three species: Boerhavia elegans (Choisy, Solanum surattense (Burm.f. and Prosopis juliflora (Sw. showed promising anti-plasmodial activity in vitro (IC50 ≤ 50 μg/ml and in vivo with no toxicity. The dichloromethane fraction of three extracts revealed stronger anti-plasmodial activity than the total extracts. Conclusion Anti-plasmodial activities of extracts of B. elegans and S. surattense are reported for the first time.

  2. Synthesis, Cytotoxic and Antimalarial Activities of Benzoyl Thiosemicarbazone Analogs of Isoquinoline and Related Compounds

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    Somsak Ruchirawat

    2010-02-01

    Full Text Available Thiosemicarbazone analogs of papaveraldine and related compounds 1–6 were synthesized and evaluated for cytotoxic and antimalarial activities. The cytotoxic activity was tested against HuCCA-1, HepG2, A549 and MOLT-3 human cancer cell lines. Thiosemicarbazones 1–5 displayed cytotoxicity toward all the tested cell lines, while compounds 2–5 selectively showed potent activity against the MOLT-3 cell lines. Significantly, N(4-phenyl-2-benzoylpyridine thiosemicarbazone 4 exhibited the most potent activity against HuCCA-1, HepG2, A549 and MOLT-3 cell lines with IC50 values of 0.03, 4.75, 0.04 and 0.004 µg/mL, respectively. In addition, 2-benzoylpyridine thio-semicarbazones 3 and 4 showed antimalarial activity against Plasmodium falciparum with IC50 of 10-7 to < 10-6 M. The study demonstrates the quite promising activity of analog 4 as a lead molecule for further development.

  3. Formulation and Particle Size Reduction Improve Bioavailability of Poorly Water-Soluble Compounds with Antimalarial Activity

    Directory of Open Access Journals (Sweden)

    Hongxing Wang

    2013-01-01

    Full Text Available Decoquinate (DQ is highly effective at killing malaria parasites in vitro; however, it is extremely insoluble in water. In this study, solid dispersion method was used for DQ formulation which created a suitable physical form of DQ in aqueous phase for particle manipulation. Among many polymers and surfactants tested, polyvinylpyrrolidone 10, a polymer, and L-α-phosphatidylcholine or polysorbate, two surfactants, were chosen as DQ formulation components. The formulation particles were reduced to a mean size between 200 to 400 nm, which was stable in aqueous medium for at least three weeks. Pharmacokinetic (PK studies showed that compared to DQ microparticle suspension, a nanoparticle formulation orally dosed to mice showed a 14.47-fold increase in area under the curve (AUC of DQ plasma concentration and a 4.53-fold increase in AUC of DQ liver distribution. WR 299666, a poorly water-soluble compound with antimalarial activity, was also tested and successfully made into nanoparticle formulation without undergoing solid dispersion procedure. We concluded that nanoparticles generated by using appropriate formulation components and sufficient particle size reduction significantly increased the bioavailability of DQ and could potentially turn this antimalarial agent to a therapeutic drug.

  4. Gas chromatographic method for the determination of lumefantrine in antimalarial finished pharmaceutical products

    Directory of Open Access Journals (Sweden)

    Sultan Suleman

    2015-09-01

    Full Text Available A simple method has been developed and validated for quantitative determination of lumefantrine in antimalarial finished pharmaceutical products using gas chromatography coupled to flame ionization detector. Lumefantrine was silylated with N,O–bis(trimethyl-silyltrifluoro-acetamide at 70°C for 30 minutes, and chromatographic separation was conducted on a fused silica capillary (HP-5, 30 m length × 0.32 mm i.d., 0.25 μm film thickness column. Evaluation of the method within analytical quality-by-design principles, including a central composite face-centered design for the sample derivatization process and Plackett–Burman robustness verification of the chromatographic conditions, indicated that the method has acceptable specificity toward excipients and degradants, accuracy [mean recovery = 99.5%, relative standard deviation (RSD = 1.0%], linearity (=0.9986, precision (intraday = 96.1% of the label claim, RSD = 0.9%; interday = 96.3% label claim, RSD = 0.9%, and high sensitivity with detection limits of 0.01 μg/mL. The developed method was successfully applied to analyze the lumefantrine content of marketed fixed-dose combination antimalarial finished pharmaceutical products.

  5. Antimalarial activity of Ageratum conyzoides in combination with chloroquine and artesunate

    Institute of Scientific and Technical Information of China (English)

    Ukwe Chinwe V; Ekwunife Obinna I; Epueke Ebele A; Ubaka Chukwuemeka M

    2010-01-01

    Objective: To determine the suppressive and curative activity of aqueous leaf extract of Ageratum conyzoides (A. conyzoides) in combination with chloroquine and artesunate, respectively against Plasmodium berghei infection in mice. Methods: Using malaria (Plasmodium berghei) infected albino mice of both sexes, aqueous extracts of A. conyzoides in combination with chloroquine and artesunate were tested for antimalarial activity, respectively. Four-day suppressive test and Rane's curative test were carried out. Results: Suppressive tests showed significant dose dependent reduction in parasitemia level produced by the extract-chloroquine and extract-artesunate combinations. Suppressive activities of both extract-drug combinations were greater than the individual drugs alone. Extract-chloroquine (100:5) produced the highest suppressive effect (98% suppression). Curative tests showed absolute survival in two extract-drug combinations. Two extract-drug combinations produced higher curative effects than the individual drugs alone. The highest dose combinations of extract-chloroquine (100:5) and extract-artesunate (100:5) produced absolute parasitemia clearance (cure) in the infected mice. Conclusions: The study indicated that aqueous extract of A. conyzoides had the ability to potentiate the antimalarial activity of chloroquine and artesunate against induced plasmodiasis in mice. It contributes a lot in the malaria endemic and poverty stricken tropics.

  6. Evaluation of the Quality of Artemisinin-Based Antimalarial Medicines Distributed in Ghana and Togo

    Directory of Open Access Journals (Sweden)

    Dorcas Osei-Safo

    2014-01-01

    Full Text Available This study, conducted as part of our overall goal of regular pharmacovigilance of antimalarial medicines, reports on the quality of 132 artemisinin-based antimalarial medicines distributed in Ghana and Togo. Three methods were employed in the quality evaluation—basic (colorimetric tests for establishing the identity of the requisite active pharmaceutical ingredients (APIs, semi-quantitative TLC assay for the identification and estimation of API content, and HPLC assay for a more accurate quantification of API content. From the basic tests, only one sample totally lacked API. The HPLC assay, however, showed that 83.7% of the ACTs and 57.9% of the artemisinin-based monotherapies failed to comply with international pharmacopoeia requirements due to insufficient API content. In most of the ACTs, the artemisinin component was usually the insufficient API. Generally, there was a good correlation between the HPLC and SQ-TLC assays. The overall failure rates for both locally manufactured (77.3% and imported medicines (77.5% were comparable. Similarly the unregistered medicines recorded a slightly higher overall failure rate (84.7% than registered medicines (70.8%. Only two instances of possible cross-border exchange of medicines were observed and there was little difference between the medicine quality of collections from border towns and those from inland parts of both countries.

  7. Discovery and Characterization of ACT-451840: an Antimalarial Drug with a Novel Mechanism of Action.

    Science.gov (United States)

    Boss, Christoph; Aissaoui, Hamed; Amaral, Nathalie; Bauer, Aude; Bazire, Stephanie; Binkert, Christoph; Brun, Reto; Bürki, Cédric; Ciana, Claire-Lise; Corminboeuf, Olivier; Delahaye, Stephane; Dollinger, Claire; Fischli, Christoph; Fischli, Walter; Flock, Alexandre; Frantz, Marie-Céline; Girault, Malory; Grisostomi, Corinna; Friedli, Astrid; Heidmann, Bibia; Hinder, Claire; Jacob, Gael; Le Bihan, Amelie; Malrieu, Sophie; Mamzed, Saskia; Merot, Aurelien; Meyer, Solange; Peixoto, Sabrina; Petit, Nolwenn; Siegrist, Romain; Trollux, Julien; Weller, Thomas; Wittlin, Sergio

    2016-09-20

    More than 40 % of the world's population is at risk of being infected with malaria. Most malaria cases occur in the countries of sub-Saharan Africa, Central and South America, and Asia. Resistance to standard therapy, including artemisinin combinations, is increasing. There is an urgent need for novel antimalarials with new mechanisms of action. In a phenotypic screen, we identified a series of phenylalanine-based compounds that exhibit antimalarial activity via a new and yet unknown mechanism of action. Our optimization efforts culminated in the selection of ACT-451840 [(S,E)-N-(4-(4-acetylpiperazin-1-yl)benzyl)-3-(4-(tert-butyl)phenyl)-N-(1-(4-(4-cyanobenzyl)piperazin-1-yl)-1-oxo-3-phenylpropan-2-yl)acrylamide] for clinical development. Herein we describe our optimization efforts from the screening hit to the potential drug candidate with respect to antiparasitic activity, drug metabolism and pharmacokinetics (DMPK) properties, and in vivo pharmacological efficacy.

  8. Formulation and particle size reduction improve bioavailability of poorly water-soluble compounds with antimalarial activity.

    Science.gov (United States)

    Wang, Hongxing; Li, Qigui; Reyes, Sean; Zhang, Jing; Xie, Lisa; Melendez, Victor; Hickman, Mark; Kozar, Michael P

    2013-01-01

    Decoquinate (DQ) is highly effective at killing malaria parasites in vitro; however, it is extremely insoluble in water. In this study, solid dispersion method was used for DQ formulation which created a suitable physical form of DQ in aqueous phase for particle manipulation. Among many polymers and surfactants tested, polyvinylpyrrolidone 10, a polymer, and L- α -phosphatidylcholine or polysorbate, two surfactants, were chosen as DQ formulation components. The formulation particles were reduced to a mean size between 200 to 400 nm, which was stable in aqueous medium for at least three weeks. Pharmacokinetic (PK) studies showed that compared to DQ microparticle suspension, a nanoparticle formulation orally dosed to mice showed a 14.47-fold increase in area under the curve (AUC) of DQ plasma concentration and a 4.53-fold increase in AUC of DQ liver distribution. WR 299666, a poorly water-soluble compound with antimalarial activity, was also tested and successfully made into nanoparticle formulation without undergoing solid dispersion procedure. We concluded that nanoparticles generated by using appropriate formulation components and sufficient particle size reduction significantly increased the bioavailability of DQ and could potentially turn this antimalarial agent to a therapeutic drug.

  9. Understanding the biology of the Plasmodium falciparum apicoplast; an excellent target for antimalarial drug development.

    Science.gov (United States)

    Chakraborty, Arnish

    2016-08-01

    Malaria is a life-threatening tropical disease, caused by the intracellular parasite Plasmodium falciparum. The World Health Organization counts malaria as one of the top ten causes of worldwide death. The unavailability of a successful malaria vaccine and the ever-increasing instances of drug resistance in the malaria parasite demand the discovery of new targets within P. falciparum for the development of next generation antimalarials. Fortunately, all apicomplexan parasites, including P. falciparum harbor a relict, non-photosynthetic plastid known as the apicoplast. The apicoplast is a semi-autonomous organelle within P. falciparum containing a 35kb circular genome. Despite a genome of its own, majority of the apicoplast proteins are encoded by the parasite nucleus and imported into the apicoplast. The organelle has been shown to be essential to P. falciparum survival and the loss the apicoplast manifests as a 'delayed death' response in the parasite. The apicoplast has evolved out of cyanobacteria in a complex, two step endosymbiotic event. As a result the architecture and the gene expression machinery of the apicoplast is quite bacteria-like and is susceptible to a wide range of antibiotics such as fosmidomycin, tetracycline, azithromycin, clindamycin and triclosan. The biosynthetic pathways for isoprenoids, fatty acids and heme operate within the malaria apicoplast, making the organelle an excellent target for drug development. The review focuses on the evolution, biology and the essentiality of the apicoplast within the malaria parasite and discusses some of the recent achievements towards the design and discovery of apicoplast targeted antimalarial compounds.

  10. Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach

    Science.gov (United States)

    Wright, Megan H.; Clough, Barbara; Rackham, Mark D.; Rangachari, Kaveri; Brannigan, James A.; Grainger, Munira; Moss, David K.; Bottrill, Andrew R.; Heal, William P.; Broncel, Malgorzata; Serwa, Remigiusz A.; Brady, Declan; Mann, David J.; Leatherbarrow, Robin J.; Tewari, Rita; Wilkinson, Anthony J.; Holder, Anthony A.; Tate, Edward W.

    2014-02-01

    Malaria is an infectious disease caused by parasites of the genus Plasmodium, which leads to approximately one million deaths per annum worldwide. Chemical validation of new antimalarial targets is urgently required in view of rising resistance to current drugs. One such putative target is the enzyme N-myristoyltransferase, which catalyses the attachment of the fatty acid myristate to protein substrates (N-myristoylation). Here, we report an integrated chemical biology approach to explore protein myristoylation in the major human parasite P. falciparum, combining chemical proteomic tools for identification of the myristoylated and glycosylphosphatidylinositol-anchored proteome with selective small-molecule N-myristoyltransferase inhibitors. We demonstrate that N-myristoyltransferase is an essential and chemically tractable target in malaria parasites both in vitro and in vivo, and show that selective inhibition of N-myristoylation leads to catastrophic and irreversible failure to assemble the inner membrane complex, a critical subcellular organelle in the parasite life cycle. Our studies provide the basis for the development of new antimalarials targeting N-myristoyltransferase.

  11. Optimization of methanol yield from a Lurgi reactor

    Energy Technology Data Exchange (ETDEWEB)

    Chen, L.; Jiang, Q.; Song, Z. [State Key Laboratory of Heavy Oil Processing, China University of Petroleum, Beijing (China); Posarac, D. [Department of Chemical and Biological Engineering, The University of British Columbia, Vancouver (Canada)

    2011-05-15

    Methanol is an important chemical with the potential to become an alternative fuel. An optimization study was performed for a Lurgi methanol synthesis reactor using the commercial process simulator Aspen Plus. The optimization routine is coupled with a steady-state model of the methanol synthesis reactor. Syngas inlet temperature, steam drum pressure, and cooling water volumetric flow rate were optimized so that methanol production in the reactor outlet was maximized. The methanol yield increased by 7.04 %. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  12. Biodegradation of methanol vapor in a biofilter

    Institute of Scientific and Technical Information of China (English)

    Durai Arulneyam; T. Swaminathan

    2003-01-01

    Volatile organic compounds (VOCs) are a new class of air pollutants posing threat to the environment. Newer technologies are being developed for their control among which biofiltration seem to be most attractive. Biofiltration of methanol vapor from air stream was evaluated in this study. Experimental investigations were conducted on a laboratory scale biofilter, containing mixture of compost and polystyrene inert particles as the filter materials. Mixed consortium of activated sludge was used as an inoculum. The continuous performance of biofilter for methanol removal was monitored for different concentrations and flow rates. The removal efficiencies decreased at higher concentrations and higher gas flow rates. A maximum elimination capacity of 85 g/(m3.h) was achieved. The response of biofilter to upset loading operation showed that the biofilm in the biofilters was quite stable and quickly adapted to adverse operational conditions.

  13. Extractive separation of micro amounts of rhenium from molybdenite by quinoline and a modified method of rhenium determination by α-furyl-dioxime

    International Nuclear Information System (INIS)

    The extractive separation of rhenium(7) by quinoline in alkaline solution as well as a modification of the spectrophotometric method for the determination of micro amounts of rhenium in a molybdenite from copper-molybdenum ores from Mongolia, using α-furyldioxime has been developed. On the basis of the extractive separation method of perrhenate ion by quinoline from alkaline solution, rhenium has been determined in molybdenite. The molybdenite was decomposed by four different methods. Two of these decomposition methods, the fusion of Na2O2 with NaOH and the sintering of CaO with KMnO4 were found as the best ones. (author)

  14. Separation, preconcentration and determination of Pb(Ⅱ) in water samples using microcrystalline triphenylmethane loaded with quinolin-8-olate

    Institute of Scientific and Technical Information of China (English)

    Li Na Hu; Zhao Gang Ren

    2009-01-01

    This paper described a novel method for the preconcentration of Pb(II) using microcrystalline triphenylmethane loaded with quinolin-8-olate prior to the determination by flame atomic absorption spectrometry. Pb(II) could be enriched by controlling appropriate condition. The preconcentration factor could reach to 200 and the detection limit of Pb(II) was 0.074 ug/L. The recovery was in a range of 93.5-103% with relative standard deviation of 1.0-2.2%. The proposed method had been successfully applied to the determination of trace Pb(II) in various water samples with satisfactory result.

  15. 4-(2-aminooxyethoxy)-2-(ethylureido)quinoline-oligonucleotide conjugates: synthesis, binding interactions, and derivatization with peptides.

    Science.gov (United States)

    Hamma, Tomoko; Miller, Paul S

    2003-01-01

    Oligo-2'-O-methylribonucleotides conjugated with 4-(2-aminooxyethoxy)-2-(ethylureido)quinoline (AOQ) and 4-ethoxy-2-(ethylureido)quinoline (EOQ) were prepared by reaction of the AOQ or EOQ phosphoramidite with the protected oligonucleotide on a controlled pore glass support. Deprotection with ethylenediamine enabled successful isolation and purification of the highly reactive AOQ-conjugated oligomer. Polyacrylamide gel electrophoresis mobility shift experiments showed that the dissociation constants of complexes formed between an AOQ- or EOQ-conjugated 8-mer and complementary RNA or 2'-O-methyl-RNA targets (9- and 10-mers) were in the low nM concentration range at 37 degrees C, whereas no binding was observed for the corresponding nonconjugated oligomer, even at a concentration of 500 nM. Fluorescence studies suggested that this enhanced affinity is most likely due to the ability of the quinoline ring of the AOQ or EOQ group to stack on the last base pair formed between the oligomer and target, thus stabilizing the duplex. The binding affinity of a 2'-O-methyl RNA 15-mer, which contained an alternating methylphosphonate/phosphodiester backbone, for a 59-nucleotide stem-loop HIV TAR RNA target, increased 2.3 times as a consequence of conjugation with EOQ. The aminooxy group of AOQ-conjugated oligomers is a highly reactive nucleophile, which reacts readily with aldehydes and ketones to form stable oxime derivatives. This feature was used to couple an AOQ-oligomer with leupeptin, a tripeptide that contains a C-terminus aldehyde group. A simple method was developed to introduce a ketone functionality into peptides that contain a cysteine residue by reacting the peptide with bromoacetone. The resulting keto-peptide was then coupled to the AOQ-oligomer. This procedure was used to prepare oligonucleotide conjugates of a tetrapeptide, RGDC, and a derivative of HIV tat peptide having a C-terminus cysteine. The combination of the unique reactivity of the aminooxy group and

  16. Cardiac damage induced by 2-amino-3-methyl-imidazo[4,5-f]quinoline in nonhuman primates.

    OpenAIRE

    Thorgeirsson, U P; Farb, A; Virmani, R.; Adamson, R. H.

    1994-01-01

    The heterocyclic aromatic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is a potent hepatocarcinogen in cynomolgus and rhesus monkeys. The finding of high cardiac IQ-DNA adduct levels prompted a histopathological study of perfusion-fixed hearts from 10 tumor-bearing monkeys chronically dosed with IQ at 10 mg/kg or 20 mg/kg 5 days per week for 48-80 months. Two monkeys dosed only with the vehicle for IQ, hydroxypropylcellulose, served as controls. All the monkeys had normal heart weights,...

  17. Dichlorido[methyl 2-(quinolin-8-yloxy-κ2N,Oacetate-κO]mercury(II

    Directory of Open Access Journals (Sweden)

    Yu-Hong Wang

    2012-07-01

    Full Text Available In the neutral title complex, [HgCl2(C12H11NO3], the HgII ion is pentacoordinated by two Cl atoms, one N atom and two weakly coordinating O atoms from the methyl 2-(quinolin-8-yloxyacetate ligand. The coordination around the HgII ion may be described as highly distorted trigonal–bipyramidal. Centrosymmetric dimers are formed by an additional weak Hg...Cl interaction, leading to a distorted octahedral coordination geometry around the HgII ion.

  18. 3-Ethyl-4-hy-droxy-8-meth-oxy-quinolin-2(1H)-one.

    Science.gov (United States)

    Kafka, Stanislav; Pevec, Andrej; Proisl, Karel; Kimmel, Roman; Košmrlj, Janez

    2012-11-01

    In the title compound, C(12)H(13)NO(3), the quinoline ring system is approximately planar with a maximum deviation from the least-squares plane of 0.058 (2) Å. In the crystal, N-H⋯O and O-H⋯O hydrogen bonds link the mol-ecules into chains running along the b-axis direction. The chains also feature π-π inter-actions between pyridine and benzene rings of inversion-related mol-ecules [centroid-centroid distance = 3.609 (2) Å].

  19. DNA adduct formation by 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) in rat colon

    OpenAIRE

    Lin, Chun-xing; Mondan, Yasumasa; Umemoto, Atsushi

    2001-01-01

    A food-born carcinogen, 2-amino-3-methylimidazo [4,5-f] quinoline (IQ) induces cancer in the rat colon. The mechanism for colonic DNA adduct formation leading to cancer by IQ was studied using a colostomized F344 rat model. In this model, the transverse colon of the rat was colostomized, which produced a fecal stream-positive proximal colon and a negative distal colon were produced. When IQ (50 mg/kg) was administered into the distal colon of the colostomized rats (n=5), the ratio of the DNA ...

  20. 2-Oxo-4-(thiophen-2-yl)-1,2,5,6-tetrahydrobenzo[h]quinoline-3-carbonitrile

    OpenAIRE

    Asiri, Abdullah M.; Faidallah, Hassan M.; Al-Youbi, Abdulrahman O.; Alamry, Khalid A.; Seik Weng Ng

    2011-01-01

    In the molecule of the title compound, C18H12N2OS, the tetrahydrobenzo[h]quinoline fused-ring system is buckled owing to the ethylene –CH2CH2– fragment, the benzene ring and the pyridine ring being twisted by 16.0 (1)°. The 4-substituted aromatic ring is bent away from the pyridine ring by 59.5 (2)° (for the major disordered thienyl component) in order to avoid crowding the cyanide substituent. In the crystal, two molecules are linked ...

  1. 2-Oxo-4-phenyl-1,2,5,6-tetra­hydro­benzo[h]quinoline-3-carbonitrile

    OpenAIRE

    Asiri, Abdullah M.; Faidallah, Hassan M.; Al-Youbi, Abdulrahman O.; Alamry, Khalid A.; Seik Weng Ng

    2011-01-01

    In the molecule of the title compound, C20H14N2O, the tetrahydrobenzo[h]quinoline fused-ring system is buckled owing to the ethylene –CH2CH2– fragment, the benzene ring and the pyridine ring being twisted by 19.7 (1)°. The 4-substituted aromatic ring is bent away from the pyridine ring by 62.9 (1)° in order to avoid crowding the cyanide substituent. In the crystal, two molecules are linked by a pair of N—H...O hydrogen bonds ...

  2. 4-(4-Bromophenyl)-2-oxo-1,2,5,6-tetrahydrobenzo[h]quinoline-3-carbonitrile

    OpenAIRE

    Asiri, Abdullah M.; Faidallah, Hassan M.; Al-Youbi, Abdulrahman O.; Alamry, Khalid A.; Seik Weng Ng

    2011-01-01

    In the molecule of the title compound, C20H13BrN2O, the tetrahydrobenzo[h]quinoline fused-ring system is buckled owing to the ethylene –CH2CH2– fragment, the benzene ring and the pyridine ring being twisted by 17.7 (1)°. The 4-substituted aromatic ring is bent away from the pyridine ring by 82.3 (1)° in order to avoid crowding the cyanide substituent. Two molecules are linked by a pair of N—H...O hydrogen bonds to form a cent...

  3. 4-(4-Methoxyphenyl)-2-oxo-1,2,5,6-tetrahydrobenzo[h]quinoline-3-carbonitrile

    OpenAIRE

    Asiri, Abdullah M.; Faidallah, Hassan M.; Al-Youbi, Abdulrahman O.; Alamry, Khalid A.; Seik Weng Ng

    2011-01-01

    In the molecule of the title compound, C21H16N2O2, the tetrahydrobenzo[h]quinoline fused-ring system is buckled owing to the ethylene –CH2CH2– fragment, the benzene ring and the pyridine ring being twisted by 19.7 (1)°. The 4-substituted aromatic ring is bent away from the pyridine ring by 50.3 (1)° in order to avoid crowding the cyanide substituent. In the crystal, two molecules are linked by a pair of N—H...O hydrogen bonds...

  4. 4-(4-Methoxyphenyl-2-oxo-1,2,5,6-tetrahydrobenzo[h]quinoline-3-carbonitrile

    Directory of Open Access Journals (Sweden)

    Abdullah M. Asiri

    2011-09-01

    Full Text Available In the molecule of the title compound, C21H16N2O2, the tetrahydrobenzo[h]quinoline fused-ring system is buckled owing to the ethylene –CH2CH2– fragment, the benzene ring and the pyridine ring being twisted by 19.7 (1°. The 4-substituted aromatic ring is bent away from the pyridine ring by 50.3 (1° in order to avoid crowding the cyanide substituent. In the crystal, two molecules are linked by a pair of N—H...O hydrogen bonds to form a centrosymmetric dimer.

  5. 4-(1,3-Benzodioxol-5-yl)-2-oxo-1,2,5,6-tetrahydrobenzo[h]quinoline-3-carbonitrile

    OpenAIRE

    Asiri, Abdullah M.; Faidallah, Hassan M.; Al-Youbi, Abdulrahman O.; Alamry, Khalid A.; Seik Weng Ng

    2011-01-01

    In the molecule of the title compound, C21H14N2O3, the tetrahydrobenzo[h]quinoline fused-ring system is buckled owing to the ethylene –CH2CH2– fragment, the benzene ring and the pyridine ring being twisted by 24.3 (1)°. The ring of the benzodioxol system is bent away from the pyridine ring by 61.4 (1)° in order to avoid crowding the cyanide substituent. Two molecules are linked by a pair of N—H...O hydrogen bonds to form a ce...

  6. 4-(1,3-Benzodioxol-5-yl-2-oxo-1,2,5,6-tetrahydrobenzo[h]quinoline-3-carbonitrile

    Directory of Open Access Journals (Sweden)

    Abdullah M. Asiri

    2011-09-01

    Full Text Available In the molecule of the title compound, C21H14N2O3, the tetrahydrobenzo[h]quinoline fused-ring system is buckled owing to the ethylene –CH2CH2– fragment, the benzene ring and the pyridine ring being twisted by 24.3 (1°. The ring of the benzodioxol system is bent away from the pyridine ring by 61.4 (1° in order to avoid crowding the cyanide substituent. Two molecules are linked by a pair of N—H...O hydrogen bonds to form a centrosymmetric dimer.

  7. 4-(4-Bromophenyl-2-oxo-1,2,5,6-tetrahydrobenzo[h]quinoline-3-carbonitrile

    Directory of Open Access Journals (Sweden)

    Abdullah M. Asiri

    2011-09-01

    Full Text Available In the molecule of the title compound, C20H13BrN2O, the tetrahydrobenzo[h]quinoline fused-ring system is buckled owing to the ethylene –CH2CH2– fragment, the benzene ring and the pyridine ring being twisted by 17.7 (1°. The 4-substituted aromatic ring is bent away from the pyridine ring by 82.3 (1° in order to avoid crowding the cyanide substituent. Two molecules are linked by a pair of N—H...O hydrogen bonds to form a centrosymmetric dimer.

  8. Natural products as starting points for future anti-malarial therapies: going back to our roots?

    Directory of Open Access Journals (Sweden)

    Wells Timothy NC

    2011-03-01

    Full Text Available Abstract Background The discovery and development of new anti-malarials are at a crossroads. Fixed dose artemisinin combination therapy is now being used to treat a hundred million children each year, with a cost as low as 30 cents per child, with cure rates of over 95%. However, as with all anti-infective strategies, this triumph brings with it the seeds of its own downfall, the emergence of resistance. It takes ten years to develop a new medicine. New classes of medicines to combat malaria, as a result of infection by Plasmodium falciparum and Plasmodium vivax are urgently needed. Results Natural product scaffolds have been the basis of the majority of current anti-malarial medicines. Molecules such as quinine, lapachol and artemisinin were originally isolated from herbal medicinal products. After improvement with medicinal chemistry and formulation technologies, and combination with other active ingredients, they now make up the current armamentarium of medicines. In recent years advances in screening technologies have allowed testing of millions of compounds from pharmaceutical diversity for anti-malarial activity in cellular assays. These initiatives have resulted in thousands of new sub-micromolar active compounds – starting points for new drug discovery programmes. Against this backdrop, the paucity of potent natural products identified has been disappointing. Now is a good time to reflect on the current approach to screening herbal medicinal products and suggest revisions. Nearly sixty years ago, the Chinese doctor Chen Guofu, suggested natural products should be approached by dao-xing-ni-shi or ‘acting in the reversed order’, starting with observational clinical studies. Natural products based on herbal remedies are in use in the community, and have the potential unique advantage that clinical observational data exist, or can be generated. The first step should be the confirmation and definition of the clinical activity of herbal

  9. Ruthenium dissolution in direct methanol fuel cells

    OpenAIRE

    Schökel, Alexander

    2015-01-01

    The lifetime of a direct methanol fuel cell (DMFC) is mostly determined by the degradation of its active component, the membrane electrode assembly (MEA). Besides degradation of the proton conducting membrane, the aging of the electrodes and especially the catalysts therein is the major limiting factor. One of the catalyst degradation mechanisms is ruthenium dissolution. This work is the first extensive study on the dissolution, migration and deposition of ruthenium in a DMFC single cell d...

  10. Studies on cluster, salt and molecular complex of zinc-quinolinate

    Indian Academy of Sciences (India)

    Prithiviraj Khakhlary; Jubaraj B Baruah

    2015-02-01

    Reactions of zinc halides with 8-hydroxyquinoline (hydroxQ) in equimolar ratio were carried out in different solvents. Respective solvates of tetranuclear clusters, namely [Zn4(oxyQ)6X2].(solvent)2, (when X=Cl, Solvent=dimethylformamide (1), dimethylacetamide (2) and dimethysulphoxide (3); X = Br, solvent = dimethylformamide (4), oxyQ=quinolinate anion) were obtained. Bond parameters of these isostructural clusteres 1–4 are compared from their single crystal structures. Anhydrous form of the cluster have porous packing and is thermally stable below 250° C. Surface area of the clusters 1 and 4 are 8.933 and 6.172 m2/g, respectively. Complexes 1 and 4 can be reversibly hydrated, which is reflected in colour changes. The reaction of zinc chloride with 8-hydroxyquinoline in equimolar ratio followed by crystallization from water gave salt (HhydroxQ)2 [ZnCl4] (5) and a similar reaction followed by crystallization from 3-methylpyridine (3mepy) resulted in the molecular complex [Zn(oxyQ)2(3mepy)]. [Zn(oxyQ)2(3mepy)2].3H2O (6). Complex 5 is formed from a hydrolytic equilibrium of water with zinc chloride yielding tetrachloro zinc anion and zinc hydroxide. Taking advantage of this reaction, a composite material of ZnO@complex 5 exhibiting dual fluorescence at 450 and 575 nm on excitation at 390 nm was prepared. Fluorescence emission properties of all the complexes in solid state are compared with fluorescence emission of the ligand

  11. Quinolinic acid induces disrupts cytoskeletal homeostasis in striatal neurons. Protective role of astrocyte-neuron interaction.

    Science.gov (United States)

    Pierozan, Paula; Ferreira, Fernanda; de Lima, Bárbara Ortiz; Pessoa-Pureur, Regina

    2015-02-01

    Quinolinic acid (QUIN) is an endogenous metabolite of the kynurenine pathway involved in several neurological disorders. Among the several mechanisms involved in QUIN-mediated toxicity, disruption of the cytoskeleton has been demonstrated in striatally injected rats and in striatal slices. The present work searched for the actions of QUIN in primary striatal neurons. Neurons exposed to 10 µM QUIN presented hyperphosphorylated neurofilament (NF) subunits (NFL, NFM, and NFH). Hyperphosphorylation was abrogated in the presence of protein kinase A and protein kinase C inhibitors H89 (20 μM) and staurosporine (10 nM), respectively, as well as by specific antagonists to N-methyl-D-aspartate (50 µM DL-AP5) and metabotropic glutamate receptor 1 (100 µM MPEP). Also, intra- and extracellular Ca(2+) chelators (10 µM BAPTA-AM and 1 mM EGTA, respectively) and Ca(2+) influx through L-type voltage-dependent Ca(2+) channel (10 µM verapamil) are implicated in QUIN-mediated effects. Cells immunostained for the neuronal markers βIII-tubulin and microtubule-associated protein 2 showed altered neurite/neuron ratios and neurite outgrowth. NF hyperphosphorylation and morphological alterations were totally prevented by conditioned medium from QUIN-treated astrocytes. Cocultured astrocytes and neurons interacted with one another reciprocally, protecting them against QUIN injury. Cocultured cells preserved their cytoskeletal organization and cell morphology together with unaltered activity of the phosphorylating system associated with the cytoskeleton. This article describes cytoskeletal disruption as one of the most relevant actions of QUIN toxicity in striatal neurons in culture with soluble factors secreted by astrocytes, with neuron-astrocyte interaction playing a role in neuroprotection.

  12. Antiperoxidative and antiinflammatory effect of Sida cordifolia Linn. on quinolinic acid induced neurotoxicity.

    Science.gov (United States)

    Swathy, S S; Panicker, Seema; Nithya, R S; Anuja, M M; Rejitha, S; Indira, M

    2010-09-01

    Sida cordifolia is a plant belonging to the Malvaceae family used in many ayurvedic preparations. This study aimed at assessing the effects of ethanolic extract of Sida cordifolia root on quinolinic acid (QUIN) induced neurotoxicity and to compare its effect with the standard drug deprenyl in rat brain. Rats were divided into six groups: (1) control group (2) QUIN (55 microg/100 g bwt/day) (3) 50% ethanolic plant extract treated group (50 mg/100 g bwt/day) (4) Deprenyl (100 microg/100 g bwt/day) (5) QUIN (55 microg/100 g bwt/day) + 50% ethanolic plant extract treated group (50 mg/100 g bwt/day) (6) QUIN (55 microg/100 g bwt/day) + Deprenyl (100 microg/100 g bwt/day). At the end of the experimental period a status of lipid peroxidation products, protein peroxidation product, activities of the scavenging enzymes and the activities of the inflammatory markers were analyzed. Results revealed that the lipid peroxidation products decreased and the activities of the scavenging enzymes increased significantly in the brain of the plant extract treated group, deprenyl treated group and also in the coadminstered groups. The activities of markers of inflammatory responses such as cyclooxygenase and lipoxygenase were found to be significantly increased in the QUIN treated rats and this was decreased upon the administration of plant extract and deprenyl. In short, the study revealed that 50% ethanolic extract of Sida cordifolia has got potent antioxidant and antiinflammatory activity and the activity is comparable with the standard drug deprenyl.

  13. Supercritical methanol for polyethylene terephthalate depolymerization: Observation using simulator

    International Nuclear Information System (INIS)

    To apply PET depolymerization in supercritical methanol to commercial recycling, the benefits of supercritical methanol usage in PET depolymerization was investigated from the viewpoint of the reaction rate and energy demands. PET was depolymerized in a batch reactor at 573 K in supercritical methanol under 14.7 MPa and in vapor methanol under 0.98 MPa in our previous work. The main products of both reactions were the PET monomers of dimethyl terephthalate (DMT) and ethylene glycol (EG). The rate of PET depolymerization in supercritical methanol was faster than that of PET depolymerization in vapor methanol. This indicates supercritical fluid is beneficial in reducing reaction time without the use of a catalyst. We depicted the simple process flow of PET depolymerization in supercritical methanol and in vapor methanol, and by simulation evaluated the total heat demand of each process. In this simulation, bis-hydroxyethyl terephthalate (BHET) was used as a model component of PET. The total heat demand of PET depolymerization in supercritical methanol was 2.35 x 106 kJ/kmol Produced-DMT. That of PET depolymerization in vapor methanol was 2.84 x 106 kJ/kmol Produced-DMT. The smaller total heat demand of PET depolymerization in supercritical methanol clearly reveals the advantage of using supercritical fluid in terms of energy savings

  14. Vibrational analysis of phenol/(methanol)1

    Science.gov (United States)

    Gerhards, M.; Beckmann, K.; Kleinermanns, K.

    1994-09-01

    Ab initio calculations at the Hartree-Fock 4-31G* level were performed in order to calculate binding energies and vibrational frequencies of the phenol/CH3OH-cluster and two deuterated isotopomers ( d-phenol/CH3OD, d-phenol-CD3OD). The minimum energy structure is trans-linear, as for the phenol/H2O-cluster. The calculated frequencies of phenol and methanol as well as the intramolecular frequencies of the phenol/CH3OH-cluster are assigned to experimental values. The calculated intermolecular frequencies of the phenol/CH3OH-cluster are compared with the available experimental frequencies of the S 0 (and S 1)-state of the phenol/methanol-cluster and the similar p-cresol/methanol-cluster. Assignments are suggested for the σ and p 1-mode. In order to clarify the assignment of the low frequency vibration at 22 cm-1 anharmonic corrections for the β2-mode of the phenol/CH3OH-cluster are calculated. These calculations show only slight anharmonicity compared with the β2-mode calculations carried out for the phenol/H2O-cluster.

  15. Photolysis of oxyfluorfen in aqueous methanol.

    Science.gov (United States)

    Chakraborty, Subhasish K; Chakraborty, Savitri; Bhattacharyya, Anjan; Chowdhury, Ashim

    2013-01-01

    Photolysis of oxyfluorfen, an herbicide of the nitrodiphenyl ether class, was studied in aqueous methanol under UV and sunlight. UV irradiation was carried out in a borosilicate glass photoreactor (containing 250 ppm oxyfluorfen in 50% aqueous methanol) equipped with a quartz filter and 125 watt mercury lamp (maximum output 254 nm) at 25 ± 1°C. Sunlight irradiation was conducted at 28 ± 1°C in borosilicate Erlenmeyer flasks containing 250 ppm oxyfluorfen in 50% aqueous methanol. The samples from both the irradiated conditions were withdrawn at a definite time interval and extracted to measure oxyfluorfen content by gas chromatography-flame ionization detector for rate study. The half-life values were 20 hours and 2.7 days under UV and sunlight exposure, respectively. Photolysis of oxyfluorfen yielded 13 photoproducts of which three were characterized by infrared spectrophotometer and (1)H NMR and (13)C NMR spectroscopy. The rest of the photoproducts were identified by gas chromatography-mass spectrometry (GC-MS) and thin layer chromatography (TLC). An ionization potential 70 eV was used for electron impact-mass spectrometry (EI-MS) and methane was used as reagent gas for chemical ionization-mass spectrometry (CI-MS). Two of the photoproducts were also synthesized for comparison. The main phototransformation pathways of oxyfluorfen involved nitro reduction, dechlorination, and hydrolysis as well as nucleophiles displacement reaction. PMID:23998303

  16. Liquid methanol under a static electric field

    Energy Technology Data Exchange (ETDEWEB)

    Cassone, Giuseppe, E-mail: giuseppe.cassone@impmc.upmc.fr [Sorbonne Universités, UPMC Univ Paris 06, UMR 7590, IMPMC, F-75005 Paris (France); CNRS, UMR 7590, IMPMC, F-75005 Paris (France); Università degli Studi di Messina, Dipartimento di Fisica e di Scienze della Terra, Contrada Papardo, 98166 Messina (Italy); CNR-IPCF, Viale Ferdinando Stagno d’Alcontres 37, 98158 Messina (Italy); Giaquinta, Paolo V., E-mail: paolo.giaquinta@unime.it [Università degli Studi di Messina, Dipartimento di Fisica e di Scienze della Terra, Contrada Papardo, 98166 Messina (Italy); Saija, Franz, E-mail: saija@ipcf.cnr.it [CNR-IPCF, Viale Ferdinando Stagno d’Alcontres 37, 98158 Messina (Italy); Saitta, A. Marco, E-mail: marco.saitta@impmc.upmc.fr [Sorbonne Universités, UPMC Univ Paris 06, UMR 7590, IMPMC, F-75005 Paris (France); CNRS, UMR 7590, IMPMC, F-75005 Paris (France)

    2015-02-07

    We report on an ab initio molecular dynamics study of liquid methanol under the effect of a static electric field. We found that the hydrogen-bond structure of methanol is more robust and persistent for field intensities below the molecular dissociation threshold whose value (≈0.31 V/Å) turns out to be moderately larger than the corresponding estimate obtained for liquid water. A sustained ionic current, with ohmic current-voltage behavior, flows in this material for field intensities above 0.36 V/Å, as is also the case of water, but the resulting ionic conductivity (≈0.40 S cm{sup −1}) is at least one order of magnitude lower than that of water, a circumstance that evidences a lower efficiency of proton transfer processes. We surmise that this study may be relevant for the understanding of the properties and functioning of technological materials which exploit ionic conduction, such as direct-methanol fuel cells and Nafion membranes.

  17. Kinetics of methanol steam reforming over COPZr-2 catalyst

    Institute of Scientific and Technical Information of China (English)

    Yongfeng Li; Weiming Lin; Lin Yu; Zhifeng Hao; Rongjian Mai

    2008-01-01

    The COPZr-2 catalyst, which was prepared in our prophase research, showed good catalytic performance in methanol steam reforming reaction. In this article, the best one was chosen as an example to study the reaction kinetics of methanol steam reforming over this type of catalyst. First, the effects of methanol conversion to outlet CO2 and methanol conversion to outlet CO on methanol pseudo contact time W/FMeOH were investigated. Then by applying the reaction route that methanol direct reforming (DR) and methanol decomposition (DE) were carried out in parallel, the reaction kinetic model with power function type was established. And the parameters for the model were estimated using a non-linear regression program which computed weighted least squares of the defined objects function. Finally, the kinetic model passed the correlation test and the F-test.

  18. Effects of the methanolic seeds extract of Carica Papaya on plasmodium Berghei infected mice

    Institute of Scientific and Technical Information of China (English)

    Amazu LU; Ebong OO; Azikiwe CCA; Unekwe PC; Siminialayi MI; Nwosu PJC; Ezeani MC; Obidiya OS; Ajugwo AO

    2009-01-01

    Objective:The leaves extract of Carica Papaya(C.Papaya)papaya has been shown to possess antimalarial ac-tivity,thus this work aims at finding out if the plants antimalarial activity is present in or extended to the seeds.Methods:The seeds of C.papaya were collected from its fruit,air dried for 5 days and ground into fine powder.80.65 g of the powder was then soaked for 48hours in 300 mL of methanol.Filtration was carried out using Whatman No.1 filter paper.The filtrate was evaporated to dryness by a three-day continuous heating on a hot plate of 30℃.The dry extract yield was scraped out of the Petri dish weighed and refrigerated until re-quired.The percentage extract yield was calculated out from the initial powder weight.A preliminary phyto-chemical study was done by re-dissolving the appropriate amount of the dry extract in distilled water and appro-priate test reagent added.The LD50 of the seeds of C.papaya was carried out using arithmetic method.Swiss albino Mice of both sexes and of average weight of 1 8-25 g were used as animals for antimalarial activity.They were housed in standard animal house,fed on Rats/Mice pellets and had non restricted excess to both feed and water throughout the 60day study period.While the non pregnant female Mice were used as test animals,the male animals were used as malaria parasite donors.Precautions were taken to ensure that all animals in the study groups were free from infection with Eperythrozoon coocoides.The female animals were then divided into three main groups (A-C)of 25 animals per group.Group A was used for malaria suppressive study (early in-fection-day 0-3)and was further subdivided to 5subgroups (a-e)of 5animals per group.Group B was used for malaria curative study (established malaria infection-day 3-7)and was further subdivided to 5subgroups (a-e) of 5animals per group.Group C was used for malaria prophylactic study (repository-4days treatment prior to malaria parasite infection)and was also further subdivided

  19. Plant-Derived Antimalarial Agents: New Leads and Efficient Phytomedicines. Part II. Non-Alkaloidal Natural Products

    Directory of Open Access Journals (Sweden)

    Alaíde Braga de Oliveira

    2009-08-01

    Full Text Available Malaria is still the most destructive and dangerous parasitic infection in many tropical and subtropical countries. The burden of this disease is getting worse, mainly due to the increasing resistance of Plasmodium falciparum against the widely available antimalarial drugs. There is an urgent need for new, more affordable and accessible antimalarial agents possessing original modes of action. Natural products have played a dominant role in the discovery of leads for the development of drugs to treat human diseases, and this fact anticipates that new antimalarial leads may certainly emerge from tropical plant sources. This present review covers most of the recently-published non-alkaloidal natural compounds from plants with antiplasmodial and antimalarial properties, belonging to the classes of terpenes, limonoids, flavonoids, chromones, xanthones, anthraquinones, miscellaneous and related compounds, besides the majority of papers describing antiplasmodial crude extracts published in the last five years not reviewed before. In addition, some perspectives and remarks on the development of new drugs and phytomedicines for malaria are succinctly discussed.

  20. Why Hospital Pharmacists Have Failed to Manage Antimalarial Drugs Stock-Outs in Pakistan? A Qualitative Insight

    Directory of Open Access Journals (Sweden)

    Madeeha Malik

    2013-01-01

    Full Text Available Purpose. This study aimed to explore the perceptions of hospital pharmacists towards drug management and reasons underlying stock-outs of antimalarial drugs in Pakistan. Methods. A qualitative study was designed to explore the perceptions of hospital pharmacists regarding drug management and irrational use of antimalarial drugs in two major cities of Pakistan, namely, Islamabad (national capital and Rawalpindi (twin city. Semistructured interviews were conducted with 16 hospital pharmacists using indepth interview guides at a place and time convenient for the respondents. Interviews, which were audiotaped and transcribed verbatim, were evaluated by thematic content analysis and by other authors’ analysis. Results. Most of the respondents were of the view that financial constraints, inappropriate drug management, and inadequate funding were the factors contributing toward the problem of antimalarial drug stock-outs in healthcare facilities of Pakistan. The pharmacists anticipated that prescribing by nonproprietary names, training of health professionals, accepted role of hospital pharmacist in drug management, implementation of essential drug list and standard treatment guidelines for malaria in the healthcare system can minimize the problem of drug stock outs in healthcare system of Pakistan. Conclusion. The current study showed that all the respondents in the two cities agreed that hospital pharmacist has failed to play an effective role in efficient management of anti-malarial drugs stock-outs.

  1. Design, synthesis and in vitro evaluation of tetrahydropyrimidine-isatin hybrids as potential antitubercular and antimalarial agents

    Institute of Scientific and Technical Information of China (English)

    Tarunkumar Nanjibhai Akhaja; Jignesh Priyakant Raval

    2012-01-01

    A series of 5-substituted-3-[{5-(6-methyl-2-oxo/thioxo-4-phenyl-1,2,3,4-tetrahydropyrimidin-5-yl)-1,3,4-oxadiazol-2-yl}-imino]-1,3-dihydro-2H-indol-2-one were synthesized,characterized and screened for their anti-tubercular and antimalarial activity.

  2. Plasmodium falciparum Thioredoxin Reductase (PfTrxR) and Its Role as a Target for New Antimalarial Discovery.

    Science.gov (United States)

    McCarty, Sara E; Schellenberger, Amanda; Goodwin, Douglas C; Fuanta, Ngolui Rene; Tekwani, Babu L; Calderón, Angela I

    2015-01-01

    The growing resistance to current antimalarial drugs is a major concern for global public health. The pressing need for new antimalarials has led to an increase in research focused on the Plasmodium parasites that cause human malaria. Thioredoxin reductase (TrxR), an enzyme needed to maintain redox equilibrium in Plasmodium species, is a promising target for new antimalarials. This review paper provides an overview of the structure and function of TrxR, discusses similarities and differences between the thioredoxin reductases (TrxRs) of different Plasmodium species and the human forms of the enzyme, gives an overview of modeling Plasmodium infections in animals, and suggests the role of Trx functions in antimalarial drug resistance. TrxR of Plasmodium falciparum is a central focus of this paper since it is the only Plasmodium TrxR that has been crystallized and P. falciparum is the species that causes most malaria cases. It is anticipated that the information summarized here will give insight and stimulate new directions in which research might be most beneficial.

  3. Plants as Sources of Antimalarial Drugs Part. 1. In vitro Test Method for the Evaluation of Crude Extracts from Plants.

    Science.gov (United States)

    O'neill, M J; Bray, D H; Boardman, P; Phillipson, J D; Warhurst, D C

    1985-10-01

    An IN VITRO antimalarial test, utilising the inhibition of uptake of [G- (3)H]-hypoxanthine into PLASMODIUM FALCIPARUM cultured in human blood, has been used to assess the activity of crude extracts of ARTEMISIA ANNUA and A. VULGARIS (Compositae) and of BRUCEA JAVANICA, AILANTHUS ALTISSIMA, and SIMABA CEDRON (Simaroubaceae).

  4. Discovery of Methanol in a Planetary Birthplace

    Science.gov (United States)

    Kohler, Susanna

    2016-05-01

    Data from the Atacama Large Millimeter/submillimeter Array (ALMA) has recently revealed the first detection of gas-phase methanol, a derivative of methane, in a protoplanetary disk. This milestone discovery is an important step in understanding the conditions for planet formation that can lead to life-supporting planets like Earth.Planetary ChemistryOne major goal in the study of exoplanets is to find planets that orbit in their host stars habitable zones, a measure that determines whether the planet receives the right amount of sunlight to support liquid water. But theres another crucial element in the formation of a life-supporting planet: chemistry.To understand the chemistry of newly born planets, we need to study protoplanetary disks because its from these that young planets form. The elements and molecules contained in these dusty disks are what initially make up the atmospheres of planets forming within the disks.The Atacama Large Millimeter/submillimeter Array under the southern sky. [ESO/B. Tafreshi]The Hunt for ComplexityThe detection of complex molecules in protoplanetary disks is an important milestone, because complex molecules are necessary to build the correct chemistry to support life. Unfortunately, detecting these molecules is very difficult, requiring observations with both high spatial resolution and high sensitivity. Thus far, though weve observed elements and simple molecules in protoplanetary disks, detections of complex molecules have been elusive with only one success before now.Luckily, we now have an observatory up to the challenge! ALMAs unprecedented spatial resolution and sensitivity has recently allowed a team of scientists led by Catherine Walsh (Leiden University) to observe gas-phase methanol in a protoplanetary disk for the first time. This detection was made in the disk around the young star TW Hya, and it represents one of the largest molecules that has ever been observed in a disk to date.Locating IcesThe model (purple line

  5. Analitical method of methanol in M85 fuels. M85 nenryochu no methanol bunsekiho

    Energy Technology Data Exchange (ETDEWEB)

    Akiyama, K.; Yasuda, H. (Japan Automobile Research Inst., Inc., Tsukuba (Japan)); Chiba, A.; Chiba, M. (Kashima Oil Co. Ltd., Tokyo (Japan)); Yamamoto, K. (Kyodo Oil Company Ltd., Tokyo (Japan))

    1990-11-01

    Within a series of work, requested by the Agency of Natural Resources and Energy, and Petroleum Energy Center, feet test is being made, by the Japan Automobile Research Institute, on automobiles, fueled by 85% methanol and 15% gasoline mixture fuel (M85). With relation to that test, study in the present report aimed at establishing and unifying analysis methods of methanol. Analysis methods, selected as objective, compeised the water extraction method, manual injection gas chromatics packed column method, automatic injection gas chromatics capillary column method (direct injection method and split injection method) and methanol concentration meter method. As a result, both the water extraction/gas chromatics method and automatic injection capillary column split injection method were confirmed, because of their reproduction accuracy and exactitude, to be first applicable. Then, the latter was concluded to be applied, because of its simplicity in procedure, smallness in personal difference, shortness in analyzing time, possibility in automation, etc. 5 refs., 3 figs., 6 tabs.

  6. Effect of substitution group on dielectric properties of 4H-pyrano [3, 2-c] quinoline derivatives thin films

    Institute of Scientific and Technical Information of China (English)

    H M Zeyada; F M El-Taweel; M M El-Nahass; M M El-Shabaan

    2016-01-01

    The AC electrical conductivity and dielectrical properties of 2-amino-6-ethyl-5-oxo-4-(3-phenoxyphenyl)-5,6-dihydro-4H-pyrano[3, 2-c]quinoline-3-carbonitrile (Ph-HPQ) and 2-amino-4-(2-chlorophenyl)-6-ethyl-5-oxo-5,6-dihydro-4H-pyrano [3, 2-c] quinoline-3-carbonitrile (Ch-HPQ) thin films were determined in the frequency range of 0.5 kHz–5 MHz and the temperature range of 290–443 K. The AC electrical conduction of both compounds in thin film form is governed by the correlated barrier hopping (CBH) mechanism. Some parameters such as the barrier height, the maximum barrier height, the density of charges, and the hopping distance were determined as functions of temperature and frequency. The phenoxyphenyl group has a greater infl uence on those parameters than the chlorophenyl group. The AC activation energies were determined at different frequencies and temperatures. The dielectric behaviors of Ph-HPQ and Ch-HPQ were inves-tigated using the impedance spectroscopy technique. The impedance data are presented in Nyquist diagrams for different temperatures. The Ch-HPQ films have higher impedance than the Ph-HPQ films. The real dielectric constant and dielectric loss show a remarkable dependence on the frequency and temperature. The Ph-HPQ has higher dielectric constants than the Ch-HPQ.

  7. Design and synthesis of novel anti-Alzheimer's agents: Acridine-chromenone and quinoline-chromenone hybrids.

    Science.gov (United States)

    Najafi, Zahra; Saeedi, Mina; Mahdavi, Mohammad; Sabourian, Reyhaneh; Khanavi, Mahnaz; Tehrani, Maliheh Barazandeh; Moghadam, Farshad Homayouni; Edraki, Najmeh; Karimpor-Razkenari, Elahe; Sharifzadeh, Mohammad; Foroumadi, Alireza; Shafiee, Abbas; Akbarzadeh, Tahmineh

    2016-08-01

    A novel series of acridine-chromenone and quinoline-chromenone hybrids were designed, synthesized, and evaluated as anti-Alzheimer's agents. All synthesized compounds were evaluated as cholinesterases (ChEs) inhibitors and among them, 7-(4-(6-chloro-2,3-dihydro-1H-cyclopenta[b]quinolin-9-ylamino)phenoxy)-4-methyl-2H-chromen-2-one (8e) exhibited the most potent anti-acetylcholinesterase (AChE) inhibitory activity (IC50=16.17μM) comparing with rivastigmine (IC50=11.07μM) as the reference drug. Also, compound 8e was assessed for its β-secretase (BACE1) inhibitory and neuroprotective activities which demonstrated satisfactory results. It should be noted that both kinetic study on the inhibition of AChE and molecular modeling revealed that compound 8e interacted simultaneously with both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. PMID:27289559

  8. Determination of mercury(II) in aquatic plants using quinoline-thiourea conjugates as a fluorescent probe.

    Science.gov (United States)

    Feng, Guodong; Ding, Yuanyuan; Gong, Zhiyong; Dai, Yanna; Fei, Qiang

    2013-01-01

    In this study, a quinoline-thiourea conjugate (1-phenyl-3-(quinoline-8-yl) thiourea, PQT) was synthesized and used as a fluorescence sensor to detect mercury ion. The observation is coincident with the well-documented phenomenon that a thiocarbonyl-containing group on a fluorochrome quenches the fluorescence due to the heavy atom effect of the S atom. The large fluorescence enhancement of PQT in the buffered MeCN-water mixture (1/1 v/v; HEPES 100 mM; pH 8.0) was caused by the Hg(2+) induced transformation of the thiourea function into a urea group. As such, protic solvents can be ascribed to hydrogen bond formation on the carbonyl oxygen to reduce the internal conversion rate. The fluorescence intensity of PQT was enhanced quantitatively with an increase in the concentration of mercury ion. The limit of detection of Hg(2+) was 7.5 nM. The coexistence of other metal ions with mercury had no obvious influence on the detection of mercury. A quinolone-thiourea conjugate was used as a fluorescent probe to detect Hg(2+) in aquatic plants and the experimental results were satisfactory. PMID:23842417

  9. Thiacalix[4]arene-tetra-(quinoline-8- sulfonate): a Sensitive and Selective Fluorescent Sensor for Co (II).

    Science.gov (United States)

    Modi, Krunal; Panchal, Urvi; Dey, Shuvankar; Patel, Chirag; Kongor, Anita; Pandya, Himanshu A; Jain, V K

    2016-09-01

    A novel fluorescent thiacalix[4]arene-tetra-(quinoline-8-sulfonate) (TCTQ8S) was synthesized by condensation of thiacalix[4]arene (TCA) and 8-quinoline sulfonyl chloride(8QSC). TCTQ8S was characterized by ESI-MS, (1)H-NMR and (13)C-NMR spectroscopic methods. TCTQ8S was found to be an efficient "turn-off" fluorescent sensor for the selective and sensitive recognition of Co(II) ions. The Job's plot measurement reveals a 1:1 stoichiometric ratio. The designed chemosensor exhibited high selectivity toward Co(II) ions vs. other tested metal ions, with a detection limit of up to 1.038 × 10(-9) M. The binding constant and quantum yield for the complex were also determined. Molecular docking studies have been successfully performed to support 1:1 binding of TCTQ8S with the Co(II) metal ion. TCTQ8S was evaluated for real sample analysis on water sample for the detection of Co(II). Graphical Abstract Thiacalix derivatized fluorescent sensor for the selective detection of Co(II). PMID:27392975

  10. Effect of substitution group on dielectric properties of 4H-pyrano [3, 2-c] quinoline derivatives thin films

    Science.gov (United States)

    H, M. Zeyada; F, M. El-Taweel; M, M. El-Nahass; M, M. El-Shabaan

    2016-07-01

    The AC electrical conductivity and dielectrical properties of 2-amino-6-ethyl-5-oxo-4-(3-phenoxyphenyl)-5,6-dihydro-4H-pyrano[3, 2-c]quinoline-3-carbonitrile (Ph-HPQ) and 2-amino-4-(2-chlorophenyl)-6-ethyl-5-oxo-5,6-dihydro-4H-pyrano [3, 2-c] quinoline-3-carbonitrile (Ch-HPQ) thin films were determined in the frequency range of 0.5 kHz-5 MHz and the temperature range of 290-443 K. The AC electrical conduction of both compounds in thin film form is governed by the correlated barrier hopping (CBH) mechanism. Some parameters such as the barrier height, the maximum barrier height, the density of charges, and the hopping distance were determined as functions of temperature and frequency. The phenoxyphenyl group has a greater influence on those parameters than the chlorophenyl group. The AC activation energies were determined at different frequencies and temperatures. The dielectric behaviors of Ph-HPQ and Ch-HPQ were investigated using the impedance spectroscopy technique. The impedance data are presented in Nyquist diagrams for different temperatures. The Ch-HPQ films have higher impedance than the Ph-HPQ films. The real dielectric constant and dielectric loss show a remarkable dependence on the frequency and temperature. The Ph-HPQ has higher dielectric constants than the Ch-HPQ.

  11. Rotation-vibration interactions in the spectra of polycyclic aromatic hydrocarbons: Quinoline as a test-case species.

    Science.gov (United States)

    Pirali, O; Kisiel, Z; Goubet, M; Gruet, S; Martin-Drumel, M A; Cuisset, A; Hindle, F; Mouret, G

    2015-03-14

    Polycyclic aromatic hydrocarbons (PAHs) are highly relevant for astrophysics as possible, though controversial, carriers of the unidentified infrared emission bands that are observed in a number of different astronomical objects. In support of radio-astronomical observations, high resolution laboratory spectroscopy has already provided the rotational spectra in the vibrational ground state of several molecules of this type, although the rotational study of their dense infrared (IR) bands has only recently become possible using a limited number of experimental set-ups. To date, all of the rotationally resolved data have concerned unperturbed spectra. We presently report the results of a high resolution study of the three lowest vibrational states of quinoline C9H7N, an N-bearing naphthalene derivative. While the pure rotational ground state spectrum of quinoline is unperturbed, severe complications appear in the spectra of the ν45 and ν44 vibrational modes (located at about 168 cm(-1) and 178 cm(-1), respectively). In order to study these effects in detail, we employed three different and complementary experimental techniques: Fourier-transform microwave spectroscopy, millimeter-wave spectroscopy, and Fourier-transform far-infrared spectroscopy with a synchrotron radiation source. Due to the high density of states in the IR spectra of molecules as large as PAHs, perturbations in the rotational spectra of excited states should be ubiquitous. Our study identifies for the first time this effect and provides some insights into an appropriate treatment of such perturbations. PMID:25770543

  12. Novel Polycarbo-Substituted Alkyl (Thieno[3,2-c]quinoline-2-Carboxylates: Synthesis and Cytotoxicity Studies

    Directory of Open Access Journals (Sweden)

    Malose Jack Mphahlele

    2014-11-01

    Full Text Available Direct one-pot base-promoted conjugate addition–elimination of 6,8-dibromo-4-chloroquinoline-3-carbaldehyde with methyl mercaptoacetate and subsequent cyclization afforded methyl [(6,8-dibromothieno[3,2-c]quinoline]-2-carboxylate. The latter undergoes Suzuki-Miyaura cross-coupling with arylboronic acids to yield exclusively the corresponding alkyl [(6,8-diarylthieno[3,2-c]quinoline]-2-carboxylates,. The cytotoxicity of the prepared compounds was evaluated against the human breast cancer cell line MCF-7 using the MTT assay. The effects of compounds 2, 3c and 4d on cell kinetics were further determined using the xCELLigence Real Time Cell Analysis (RTCA system. In both the MTT assay and Real Time Cell Analysis, the compounds inhibited cancer cell growth in a dose- and time-dependent manner. Furthermore, on the basis of the calculated LC50 values, the compounds compared favourably with nocodazole, a well-established anticancer drug.

  13. Safety and tolerability of combination antimalarial therapies for uncomplicated falciparum malaria in Ugandan children

    Directory of Open Access Journals (Sweden)

    Kamya Moses R

    2008-06-01

    Full Text Available Abstract Background Combination antimalarial therapy is recommended for the treatment of uncomplicated falciparum malaria in Africa; however, some concerns about the safety and tolerability of new regimens remain. This study compared the safety and tolerability of three combination antimalarial regimens in a cohort of Ugandan children. Methods A longitudinal, single-blind, randomized clinical trial of children was conducted between November 2004 and May 2007 in Kampala, Uganda. Upon diagnosis of the first episode of uncomplicated malaria, participants were randomized to treatment with amodiaquine + sulphadoxine-pyrimethamine (AQ+SP, artesunate + amodiaquine (AS+AQ, or artemether-lumefantrine (AL. Once randomized, participants received the same regimen for all subsequent episodes of uncomplicated malaria. Participants were actively monitored for adverse events for the first 14 days after each treatment, and then passively followed until their next study medication treatment, or withdrawal from study. Outcome measures included the risk of adverse events at 14 and 42 days after treatment. Results Of 601 enrolled children, 382 were diagnosed with at least one episode of uncomplicated malaria and were treated with study medications. The median age at treatment was 6.3 years (range 1.1 – 12.3 years. At 14 days of follow-up, AQ+SP treatment was associated with a higher risk of anorexia, weakness, and subjective fever than treatment with AL, and a higher risk of weakness, and subjective fever than treatment with AS+AQ. Treatment with AL was associated with a higher risk of elevated temperature. Repeated episodes of neutropaenia associated with AS+AQ were detected in one participant. Considering only children less than five years, those who received AQ+SP were at higher risk of developing moderate or severe anorexia and weakness than those treated with AL (anorexia: RR 3.82, 95% CI 1.59 – 9.17; weakness: RR 5.40, 95% CI 1.86 – 15.7, or AS

  14. Minimizing the Entropy Production of the Methanol Producing Reaction in a Methanol Reactor

    OpenAIRE

    Dick Bedeaux; Lars Nummedal; Audun Rosjorde; Eivind Johannessen; Signe Kjelstrup

    2000-01-01

    The entropy production of the reaction that produces methanol in a methanol reactor, has been minimized. The results show that the entropy production of the reaction can be reduced by more than 70%. The optimal path through the reactor is characterized by a driving force for the chemical reaction that is close to constant. The entropy production due to heat transfer across the reactor walls in this state is large, however. Variations of the reactor design show that it is possible to ...

  15. Convenient synthesis of 2,2-Dimethyl-3,4-dihydro-2 H-pyrano[2,3- b]quinolines

    Digital Repository Service at National Institute of Oceanography (India)

    Parsekar, S.B.; Amonkar, C.P.; Parameswaran, P.S.; Tilve, S.G.

    A convenient general synthesis of 2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]quinolines using the Wittig reaction is described. The o-nitrobenzaldehydes (1a-d) on reaction with phosphorane 2 provided (E)-ethyl-a-(2,2-dimethylprop-2-ene)-2...

  16. An efficient ultrasound promoted catalyst-free protocol for the synthesis of chromeno[4,3-b]quinolin-6-ones

    Indian Academy of Sciences (India)

    J Venkata Prasad; J Satyanarayana Reddy; N Ravi Kumar; K Anand Solomon; G Gopikrishna

    2011-09-01

    A convenient, catalyst-free protocol for the quantitative synthesis of fused chromeno[4,3-b]quinolin-6-ones has been developed by simple one-pot reaction of substituted anilines with 4-chloro-3-formylcoumarin using ultrasound irradiation. The protocol offers the advantages of mild reaction conditions, short reaction times and high yields.

  17. Simple and practical synthesis of pyrano- and furano[3,2-c]-quinoline derivatives under non-Lewis acid catalysis

    Institute of Scientific and Technical Information of China (English)

    Rui Huan Liu; Xin Yu; Liang Hu; Nie Fang Yu

    2012-01-01

    One-pot synthesis of substituted pyrano- and furano[3,2-c]quinoline derivatives from appropriately substituted anilines,substituted benzaldehydes and dienophiles via Povarov reaction catalyzed by HCl-ethanol were reported.Good to excellent yields with high diastereoselectivity were obtained in all entries tested.

  18. C8-Selective Acylation of Quinoline N-Oxides with α-Oxocarboxylic Acids via Palladium-Catalyzed Regioselective C-H Bond Activation.

    Science.gov (United States)

    Chen, Xiaopei; Cui, Xiuling; Wu, Yangjie

    2016-08-01

    A facile and efficient protocol for palladium-catalyzed C8-selective acylation of quinoline N-oxides with α-oxocarboxylic acids has been developed. In this approach, N-oxide was utilized as a stepping stone for the remote C-H functionalization. The reactions proceeded efficiently under mild reaction conditions with excellent regioselectivity and broad functional group tolerance. PMID:27441527

  19. Discovery of Quinoline-Derived Trifluoromethyl Alcohols, Determination of Their in vivo Toxicity and Anticancer Activity in a Zebrafish Embryo Model.

    Science.gov (United States)

    Sittaramane, Vinoth; Padgett, Jihan; Salter, Philip; Williams, Ashley; Luke, Shauntelle; McCall, Rebecca; Arambula, Jonathan F; Graves, Vincent B; Blocker, Mark; Van Leuven, David; Bowe, Keturah; Heimberger, Julia; Cade, Hannah C; Immaneni, Supriya; Shaikh, Abid

    2015-11-01

    In this study the rational design, synthesis, and anticancer activity of quinoline-derived trifluoromethyl alcohols were evaluated. Members of this novel class of trifluoromethyl alcohols were identified as potent growth inhibitors in a zebrafish embryo model. Synthesis of these compounds was carried out with an sp(3) -C-H functionalization strategy of methyl quinolines with trifluoromethyl ketones. A zebrafish embryo model was also used to explore the toxicity of ethyl 4,4,4-trifluoro-3-hydroxy-3-(quinolin-2-ylmethyl)butanoate (1), 2-benzyl-1,1,1-trifluoro-3-(quinolin-2-yl)propan-2-ol (2), and trifluoro-3-(isoquinolin-1-yl)-2-(thiophen-2-yl)propan-2-ol (3). Compounds 2 and 3 were found to be more toxic than compound 1; apoptotic staining assays indicated that compound 3 causes increased cell death. In vitro cell proliferation assays showed that compound 2, with an LC50 value of 14.14 μm, has more potent anticancer activity than cisplatin. This novel class of inhibitors provides a new direction in the discovery of effective anticancer agents.

  20. Chemical composition of essential oils of Piper jacquemontianum and Piper variabile from Guatemala and bioactivity of the dichloromethane and methanol extracts

    Directory of Open Access Journals (Sweden)

    Sully M. Cruz

    2011-08-01

    Full Text Available The essential oils from two native species from Guatemala were studied for their chemical composition and the dichloromethane and methanol extracts for their biological activity. A GC-MS analysis of the essential oil from Piper jacquemontianum Kunth, Piperaceae, showed 34 constituents, consisting mainly of linalool (69.4%, while Piper variabile C. DC. essential oil had 36 constituents, camphor (28.4%, camphene (16.6% and limonene (13.9% being the major components. Dichloromethane extracts of both species were cytotoxic against MCF-7, H-460 and SF-268 cell lines (<7 µg/mL. Dichloromethane extract of P. jacquemontianum was slightly active against bacteria (0.5 mg/mL, was active against promastigotes of Leishmania (20.4-61.0 µg/mL, and epimastigotes of Trypanosoma cruzi (51.9 µg/mL. The methanol extract of P. variabile showed antimalarial activity against Plasmodium falciparum F32 (4.5 µg/mL, and the dichloromethane extract against Leishmania (55.8-76.3 µg/mL and T. cruzi (45.8 µg/mL. None of the extracts from the two species was active against Aedes aegypti larvae and Artemia salina nauplii.