Sample records for benzimidazoles

  1. Benzimidazoles Pharmacodynamics in Equine Strongyles

    Directory of Open Access Journals (Sweden)

    Laura Catana


    Full Text Available Our research aimed to assess the effectiveness of four benzimidazoles: albendazole, fenbendazole, mebendazole and thiabendazole against equine strongyles. The tests were performed between March 2015 and May 2016, on samples collected from 20 horses and 8 donkeys living in Harghita County. In vivo, Faecal Egg Count Reduction Test (FECRT was used to evaluate fenbendazole pharmacodynamics. In vitro, Egg hatch assay (EHA and Larval development assay (LDA were used to evaluate the effectiveness of albendazole, fenbendazole, mebendazole and thiabendazole. The predominance of small strongyle species was observed, mostly Cyathostomum type A. In the horse group, before treatment, the average intensity was 1595.5 EPG, the maximum value being 4000, and extensivity 55%. Tested again at 14 days after treatment, all samples were negative. In the donkey group, before treatment, the total number was 6550 EPG, intensity of 935.7 and extensivity of 87.5%. 14 days after treatment, the average intensity was 150 and the extensivity 50%. In the horse group, EHA proved the efficacy of fenbendazole (0.0192%, albendazole (0.3740% and thiabendazole (11.62% and a major risk of inducing adaptive phenomena for mebendazole (Y parameter 1009.92. In the donkey group, all benzimidazoles had limited effectiveness: thiabendazole (73.93%, mebendazole (87.51%, fenbendazole (94.05%, albendazole (111.67%. All benzimidazoles inhibited larval development. For all tested benzimidazoles, the resistance induction predictive comparative risk analysis highlighted the benefit of their use, provided that the treatment protocol allows sufficient contact time.


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    Ankur Shukla


    Full Text Available The synthesis of benzimidazoles derivative involves subsequent synthesis of 4-(2-chloro-ethoxy-benzaldehyde, 4 methyl benzaldehyde followed by benzimidazoles derivative by reaction between amines derivatives and o-phenylenediamine in dimethyl farmamide (DMF as solvent in the presence of iodine as a catalyst. Iodine is a commercial and environmentally benign catalyst. The yield of all benzimidazole derivatives was found to be in the range of 75 – 94%. The purity of the compounds was ascertained by melting point and TLC. The synthesized compounds were characterized by using IR,1H NMR, and MASS spectral data together with elemental analysis. The synthesized benzimidazole compounds were screened for analgesic and anticonvulsant activity in albino rat (100-200gm by using Writhing test and maximal electroshock (MES. Out of all compound studied only PS-3, PS-4, PS-5 and PS-6 showed significant analgesic activities and response against MES test.

  3. Chiral benzimidazoles as hydrogen bonding organocatalysts


    Nájera Domingo, Carmen; Yus Astiz, Miguel


    Several bifunctional organocatalysts bearing the benzimidazole unit have been designed in order to act as bifunctional systems by hydrogen bonding. Chiral 2-aminobenzimidazoles are conformational rigid guanidines able to catalyze enantioselectively Michael reaction, direct SN1 of alcohols, and aldol reactions. Some of these organocatalysts can be easily recovered by simple isolation methods and reused without loss of catalytic activity. Related (2-aminoalkyl)benzimidazoles have been used as c...

  4. Benzimidazole resistance in equine cyathostomins in India. (United States)

    Kumar, Sunil; Garg, Rajat; Kumar, Saroj; Banerjee, P S; Ram, Hira; Prasad, A


    Benzimidazole resistance is a major hindrance to the control of equine cyathostominosis throughout the world. There is a paucity of knowledge on the level of benzimidazole resistance in small strongyles of horses in India. In the present study, allele-specific PCR (AS-PCR) that detects F200Y mutation of the isotype 1 β-tubulin gene and faecal egg count reduction test (FECRT) were used for detecting benzimidazole resistance in equine cyathostomin populations in different agro-climatic zones of Uttar Pradesh, India. Results of the FECRT revealed prevalence of benzimidazole resistance in cyathostomins in an intensively managed equine farm in the mid-western plain (FECR=27.5%, LCI=0) and in working horses (extensively managed) at three locations in central plains of Uttar Pradesh (FECR=75.7-83.6%, LCI=29-57%). Post-treatment larval cultures revealed the presence of exclusively cyathostomin larvae. Genotyping of cyathostomin larvae by AS-PCR revealed that the frequency of homozygous resistant (rr) individuals and the resistant allele frequency was significantly higher (pIndia, necessitates immediate replacement of the drugs of benzimidazole group with other unrelated effective anthelmintics for management and control of equine cyathostomins.

  5. Facile Synthesis of N -Substituted Benzimidazoles

    NARCIS (Netherlands)

    Kurhade, Santosh; Rossetti, Arianna; Dömling, Alexander


    A particularly mild and efficient one-pot synthesis of N-substituted benzimidazole derivatives was developed. 2-Fluoro-5-nitrophenylisocyanide reacts with a diverse set of primary amines to afford the respective products in moderate to very good yield (35-95%; 20 examples).

  6. Recent Development of Benzimidazole-Containing Antibacterial Agents. (United States)

    Song, Di; Ma, Shutao


    Clinically significant antibiotic resistance is one of the greatest challenges of the twenty-first century. However, new antibacterial agents are currently being developed at a much slower pace than our growing need for such drugs. Given their diverse biological activities and clinical applications, many bioactive heterocyclic compounds containing a benzimidazole nucleus have been the focus of interest for many researchers. The benzimidazole nucleus is a structural isostere of naturally occurring nucleotides. This advantage allows benzimidazoles to readily interact with the various biopolymers found in living systems. In view of this situation, much attention has been given to the exploration of benzimidazole-based antibacterial agents, leading to the discovery of many new chemical entities with intriguing profiles. In this minireview we summarize novel benzimidazole derivatives active against various bacterial strains. In particular, we outline the relationship between the structures of variously modified benzimidazoles and their antibacterial activity.


    Directory of Open Access Journals (Sweden)

    E. I. Mayboroda


    Full Text Available The literature data about antibacterial properties of benzimidazole 2-thio-, 2-aminoderivatives and benzimidazole complexes have been generalized and systematized in the review. Today prevention and treatment of diseases caused by microorganisms is an actual problem of modern therapy. Therefore, the search for active molecules, the based on them development of some new, more effective antimicrobial agents is an important task of modern pharmaceutical chemistry. Promising compounds for solving these problems are benzimidazole derivatives. They are available, functionally capable, stable and have a wide spectrum of biological activities (antiviral, anthelmintic, antibacterial, anticancer, antidiabetic.The purpose of this paper is to generalize and systematize information about the antimicrobial action of 2-thio-, 2-amino-substituted benzimidazoles and benzimidazole derivatives complexes with transition metals.These compounds and their complexes with transition metals are active against pathogenic strains Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhimurium, Proteus vulgaris, Bacillus cereus, Micrococcus luteus, Helicobacter рylori and others.

  8. Simple, mild, and highly efficient synthesis of 2-substituted benzimidazoles and bis-benzimidazoles

    Energy Technology Data Exchange (ETDEWEB)

    Eren, Bilge, E-mail: [Faculty of Science and Arts, Department of Chemistry, Bilecik Seyh Edebali University, (Turkey); Bekdemir, Yunus [Faculty of Science and Arts, Canik Basari University, Samsun (Turkey)


    A new convenient method for preparation of 2-substituted benzimidazoles and bis-benzimidazoles is presented. In this method, o-phenylenediamines were condensed with bisulfite adducts of various aldehydes and di-aldehydes under neat conditions by microwave heating. The results were also compared with results of synthesis by conventional heating under reflux. Structures of the products were confirmed by infrared, {sup 1}H- and {sup 13}C-NMR spectroscopy. Short reaction times, good yields, easy purification of products, and mild reaction conditions are the main advantages of this method. (author)

  9. Derivatives of benzimidazole: vasodilator activity of 2-(p-chloro-alpha-hydroxybenzyl)-benzimidazole hydrochloride. Preliminary study. (United States)

    Demenge, P; Carraz, G; Luu Duc, C; Silice, C


    The effects of 2-(p-chloro-alpha-hydroxybenzyl)-benzimidazole hydrochloride (HBBPC) have been studied in the rabbit and rat. Most of these studies were performed comparatively with reference vasodilators and papaverine. HBBPC vasodilator activity is nearly the same as that of papaverine in the isolated rabbit ear. The characteristic of the vasoactive action of HBBPC seems to reside in its duration. The mechanism of action of HBBPC seems of peripheral type, that is to say it acts on the vascular smooth muscle.

  10. Synthesis of Some New Benzimidazole Derivatives of Pharmaceutical Interest


    Fawzia Zakaria El-Ablack


    Reaction of 2-(aminomethyl)benzimidazole dihydrochloride (1) with ethyl acetoacetate was studied to give diazepinone-benzimidazole derivative (2), while, treatment of 1 with phenylhydrazono ethylacetoacetate afforded phenylhydrazino diazepinone derivative (3). On the other hand, reaction of 1 with acetyl acetone resulted in the formation of diazepine derivative (4). The reaction of 1 with ethyl cyanoacetate was studied to give 3-aminodiazepinone derivative (5). Also the reaction of 1 with ace...

  11. Screening of Trichoderma strains tolerant to benzimidazole

    Institute of Scientific and Technical Information of China (English)

    LIU Kai-qi; XIANG Mei-mei; LIU Ren; ZENG Yong-san; ZHOU Hong-zi; YU Jin-feng; JIANG Xin-yin; ZHANG Yue-li


    @@ The screening of isolates and the assay of biocontrol mechanisms of Trichoderma were studied systematically in laboratory and greenhouse in vivo. The proteins tolerant to benzimidazole in Trichoderma strains were purified, and their physical and chemical properties were detected. Compared their biological activities in vitro and vivo in greenhouse, nine biocontrol strains (including Ty- 10-2, LTR-2, Tj-5-1, Tj-5-4, Ty- 11-1, Tj-11-3, Ty- 11-3, Tj-3-3-2, Tj-3-3-4) were screened. These biocontrol strains had faster rates of growth and higher inhibition to gray mould (Bortrytis cinerea),and the inhibition was stable. The effects of controlling gray mould in greenhouse with the screened Trichoderma strains were 70 % and 50 % in vivo.

  12. Detection of benzimidazole carbamates and amino metabolites in liver by surface plasmon resonance-biosensor (United States)

    Two surface plasmon resonance (SPR) biosensor screening assays were developed and validated to detect 11 benzimidazole carbamate (BZT) and four amino-benzimidazole veterinary drug residues in liver tissue. The assays used polyclonal antibodies, raised in sheep, to detect BZTs and amino-benzimidazole...

  13. Growth and properties of benzil doped benzimidazole (BMZ) single crystals

    Energy Technology Data Exchange (ETDEWEB)

    Babu, R. Ramesh, E-mail: [Crystal Growth and Thin Film Laboratory, School of Physics, Bharathidasan University, Tiruchirappalli 620 024 (India); Crystal Growth and Crystallography Section, National Physical Laboratory, Krishnan Marg, New Delhi 110 012 (India); Sukumar, M. [Crystal Growth and Thin Film Laboratory, School of Physics, Bharathidasan University, Tiruchirappalli 620 024 (India); Vasudevan, V. [Crystal Growth and Thin Film Laboratory, School of Physics, Bharathidasan University, Tiruchirappalli 620 024 (India); Crystal Growth and Crystallography Section, National Physical Laboratory, Krishnan Marg, New Delhi 110 012 (India); Shakir, Mohd. [Crystal Growth and Crystallography Section, National Physical Laboratory, Krishnan Marg, New Delhi 110 012 (India); Ramamurthi, K. [Crystal Growth and Thin Film Laboratory, School of Physics, Bharathidasan University, Tiruchirappalli 620 024 (India); Bhagavannarayana, G. [Crystal Growth and Crystallography Section, National Physical Laboratory, Krishnan Marg, New Delhi 110 012 (India)


    In the present work, we have made an attempt to study the effect of benzil doping on the properties of benzimidazole single crystals. For this purpose we have grown pure and benzil doped benzimidazole single crystals by vertical Bridgman technique. The grown crystals were characterized by various characterization techniques. The presence of dopants confirmed by powder X-ray diffraction (XRD). Crystalline perfection of the grown crystals has been analysed by high-resolution X-ray diffraction (HRXRD). The transmittance, electrical property and mechanical strength have been analysed using UV-vis-NIR spectroscopic, dielectric and Vicker's hardness studies. The relative second harmonic generation efficiency of pure and doped benzimidazole crystals measured using Kurtz powder test.

  14. Benzimidazole resistance in equine cyathostomes in Slovakia. (United States)

    Várady, M; Königová, A; Corba, J


    The present study included 19 stud farms, including 243 horses, that were investigated for the occurrence of anthelmintic resistant cyathostomes. The number of horses on the farms varied from nine to more than 100, and horses of all ages were included. A minimum of seven horses were used for faecal egg count reduction (FECR) tests. The anthelmintics included were: fenbendazole (paste formulation), ivermectin (paste formulation) and pyrantel (powder). Resistance to benzimidazoles was detected on 14 farms, with FECR values ranging from 65.1 to 86.3%. Larval cultures after fenbendazole treatment revealed exclusively cyathostome larvae. Ivermectin was tested on eight farms and proved to be effective on all. Pyrantel was tested on two farms and FECR test indicated high efficacy (92-97%). Egg hatch assay (EHA) results showed that mean concentrations of thiabendazole that inhibited hatching in 50% of the eggs (ED(50)) in resistant populations were over 0.1 microg ml(-1). The results of our study suggest widespread resistance to fenbendazole in equine cyathostomes in Slovakia, and possible strategies to delay anthelmintic resistance are discussed briefly.

  15. Development of QSAR for antimicrobial activity of substituted benzimidazoles. (United States)

    Vashist, N; Sambi, S S; Kumar, P; Narasimhan, B


    QSAR analysis has been done to correlate antimicrobial activity of substituted benzimidazole derivatives with their physicochemical parameters. Developed QSAR models have been cross validated using leave one out (LOO) method. Statistical parameters like probable error of the coefficient of correlation (PE), least square error (LSE), Friedman's lack of fit measure (LOF), standard error of prediction (SEP) and quality value (Q) were also used to cross validate the models. QSAR studies established the importance of WAP, Mlog P and UI in describing the antimicrobial activities of substituted benzimidazole derivatives.

  16. Benzimidazole grafted polybenzimidazoles for proton exchange membrane fuel cells

    DEFF Research Database (Denmark)

    Yang, Jingshuai; Aili, David; Li, Qingfeng


    High molecular weight polybenzimidazole (PBI) was synthesized and grafted with benzimidazole pendant groups. The high molecular weight of PBI resulted in good film-forming properties and superior tensile strength. With a phosphoric acid doping level (ADL) of 13.1, a tensile strength of 16 MPa was...

  17. Novel benzimidazole-based MCH R1 antagonists. (United States)

    Carpenter, Andrew J; Al-Barazanji, Kamal A; Barvian, Kevin K; Bishop, Michael J; Britt, Christy S; Cooper, Joel P; Goetz, Aaron S; Grizzle, Mary K; Hertzog, Donald L; Ignar, Diane M; Morgan, Ronda O; Peckham, Gregory E; Speake, Jason D; Swain, Will R


    The identification of an MCH R1 antagonist screening hit led to the optimization of a class of benzimidazole-based MCH R1 antagonists. Structure-activity relationships and efforts to optimize pharmacokinetic properties are detailed along with the demonstration of the effectiveness of an MCH R1 antagonist in an animal model of obesity.

  18. Systemic study on fluorescent switching systems composed of naphthopyran and benzimidazole in solution and film forms (United States)

    He, Yi; Wang, Guang; Wang, Mingxin


    The fluorescent photo-switching systems were prepared based on fluorescent benzimidazole and photochromic naphthopyran. Naphthopyran in this systems displayed excellent photochromic performance in tetrahydrofuran solutions and in PMMA films. The fluorescent emission of benzimidazole was modulated between "on" and "off" via the photoisomerization of naphthopyran in high-contrast due to the photoinduced energy transfer from benzimidazole to the open-form naphthopyran. Both the fluorescent photoswitching and the photochromism of benzimidazole-naphthopyran dyads in solutions and films displayed excellent fatigue resistance. The spaces between benzimidazole and naphthopyran affect the absorbance and fluorescence spectra of benzimidazole-naphthopyran dyads. The non-destructive readout ability of synthesized dyads in doped PMMA film was achieved.

  19. Synthesis, spectral correlation and insect antifeedant activities of some 2-benzimidazole chalcones



    Some substituted styryl 2-benzimidazole ketones have been synthesised by fly-ash:H2SO4 catalysed aldol condensation of 2-benzimidazole methyl ketone and various substituted benzaldehydes in microwave oven. The yields of these chalcones are more than 70%. The purities of synthesised benzimidazole chalcones were checked by their physical constants and spectral data earlier published in the literature. The spectral frequencies of these chalcones have been correlated with Hammett substituent cons...

  20. Synthesis and crystal structure of ethyl benzimidazole-2-yl phosphonate

    Institute of Scientific and Technical Information of China (English)

    HU, Fang-Zhong; WENG, Lin-Hong; YANG, Hua-Zheng; ZOU, Xiao-Mao


    When N-cyanoimido- ( O, O-diethyl ) phosphonyl/ S-methyl thiocarbonate (1) was treated with o-phenylenediamine in the presence of Et3N in ethanol, diethyl benzimidazole-2-yl recrys phonate(2) was obtained and hydrolyzed during the recrys tallization in MeOH/H2O, generating ethyl benzimidazole-2-yl phosphonate(3). The crystal structure of compound 3 was determined by X-ray diffraction method. The crystals belong to monoclinic, space rgoup C2/c, a=1.78408(18), b=O. 83725(9), c=1.67401(18) nm, β= 118.997(2)°, v=2. 1870(4) nm3, z=8, Dc=1.374g/cm3, F(000)=944.The final R and wR are 0.0499 and 0.1436, respectively. The mechanism of the above reaction is also discussed.

  1. The Target of Benzimidazole Carbamate Against Cysticerci cellulosae

    Institute of Scientific and Technical Information of China (English)

    LI Qing-zhang; HAO Yan-hong; GAO Xue-jun; GAO Wen-xue; ZHAO Bing


    To study the target of benzimidazole carbamate drugs against Cysticerci cellulosae and give a theoretical basis for type evolution and new drug design, the changes of key enzyme activities and metabolite contents in the pathway of energy metabolism in C. cellulosae in vitro and in vivo were tested with albendazole and oxfendazole, respectively. Both albendazole and oxfendazole inhibited the pathways of anaerobic glycolysis, partial inversed tricarboxylic acid cycle of Taenia Solium oncosphere, immature and mature Cysticerci in vitro, and immature and mature Cysticerci in vivo to a certain degree, and enhanced fat decomposing, amino acid decomposing, xanthine decomposing metabolism, and on the other hand, the absorption of glucose was hindered; furthermore, both albendazole and oxfendazole inhibited the activities of the fumaric reductase (FR) complex noncompetently in vitro. Benzimidazole carbamate drugs could inhibit the activities of FR complex noncompetently and hinder the absorption of glucose.

  2. Antibacterial and antifungal activities of benzimidazole and benzoxazole derivatives.


    Elnima, E I; Zubair, M U; Al-Badr, A A


    The in vitro antibacterial and antifungal activities of six benzimidazole and benzoxazole derivatives were tested against standard strains and 59 clinical isolates. Of the six compounds, only compounds II and III (both benzoxazoles) were active, whereas the rest were devoid of any activity. Considerable growth inhibition of all of the standard strains, including fungi and gram-positive and gram-negative bacteria, resulted when they were treated with these compounds. Fifty-nine clinical isolat...

  3. Synthesis and photophysical characterization of novel triphenylamine-benzimidazole derivatives


    Batista, Rosa Maria Ferreira; Pina, J.; de Melo, J. Seixas; Costa, Susana P. G.; Raposo, M. Manuela M.


    Research on organic luminescent materials has been intensely pursued due to their importance in technological applications related to signaling, fluorescent biosensory/chemosensory materials, molecular switches and organic light emitting diodes (OLEDs). Organic fluorophores such as triphenylamine and benzimidazole derivatives have attracted a particular attention owing to their high emission efficiency being widely used as electron transporters and emitting layers for OLEDs.1 Recently, we ...

  4. Gold complexes with benzimidazole derivatives: synthesis, characterization and biological studies. (United States)

    Mota, Vinicius Zamprogno; de Carvalho, Gustavo Senra Gonçalves; da Silva, Adilson David; Costa, Luiz Antônio Sodré; de Almeida Machado, Patrícia; Coimbra, Elaine Soares; Ferreira, Carmen Veríssima; Shishido, Silvia Mika; Cuin, Alexandre


    Synthesis, characterization, DFT studies and biological assays of new gold(I) and gold(III) complexes of benzimidazole are reported. Molecular and structural characterizations of the compounds were based on elemental (C, H and N) and thermal (TG-DTA) analyses, and FT-IR and UV-Visible spectroscopic measurements. The structures of complexes were proposed based DFT calculations. The benzimidazole compounds (Lig1 and Lig2) and the gold complexes were tested against three Leishmania species related to cutaneous manifestations of leishmaniasis. The free benzimidazole compounds showed no leishmanicidal activity. On the other hand, the gold(I and III) complexes have shown to possess significant activity against Leishmania in both stages of parasite, and the gold(III) complex with Lig2 exhibited expressive leishmanicidal activity with IC50 values below 5.7 μM. Also, the gold complexes showed high leishmania selectivity. The gold(I) complex with Lig1, for example, is almost 50 times more toxic for the parasite than for macrophages. Besides the leishmanicidal activity, all complexes exhibited toxic effect against SK-Mel 103 and Balb/c 3T3, cancer cells.

  5. 1,3,5-Trimethylpyrazolium chloride based ionogel as an efficient and reusable heterogeneous catalyst for the synthesis of benzimidazoles

    Indian Academy of Sciences (India)

    Pankaj Sharma; Monika Gupta


    A new approach for the synthesis of benzimidazoles using ionogel under solvent-free conditions is reported. Catalytic activity of ionogel was compared with silica coated with ionic liquid (silica-IL) and it was found that ionogel is highly active compared to silica-IL for the synthesis of benzimidazoles. Moreover, ionogel was recyclable for the synthesis of benzimidazoles.

  6. A bioassay for the detection of benzimidazoles reveals their presence in a range of environmental samples

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    Terence S Crofts


    Full Text Available Cobamides are a family of enzyme cofactors that include vitamin B12 (cobalamin and are produced solely by prokaryotes. Structural variability in the lower axial ligand has been observed in cobamides produced by diverse organisms. Of the three classes of lower ligands, the benzimidazoles are uniquely found in cobamides, whereas the purine and phenolic bases have additional biological functions. Many organisms acquire cobamides by salvaging and remodeling cobamides or their precursors from the environment. These processes require free benzimidazoles for incorporation as lower ligands, though the presence of benzimidazoles in the environment has not been previously investigated. Here, we report a new purification method and bioassay to measure the total free benzimidazole content of samples from microbial communities and laboratory media components. The bioassay relies on the calcofluor-bright phenotype of a bluB mutant of the model cobalamin-producing bacterium Sinorhizobium meliloti. The concentrations of individual benzimidazoles in these samples were measured by liquid chromatography-tandem mass spectrometry. Several benzimidazoles were detected in subpicomolar to subnanomolar concentrations in host-associated and environmental samples. In addition, benzimidazoles were found to be common contaminants of laboratory media components. These results suggest that benzimidazoles present in the environment and in laboratory media have the potential to influence microbial metabolic activities.

  7. Synthesis of Some Benzimidazole Derivatives Bearing 1,3,4-Oxadiazole Moiety as Anticancer Agents. (United States)

    Mochona, Bereket; Mazzio, Elizabeth; Gangapurum, Madhavei; Mateeva, Nelly; Redda, K K


    In an effort to establish new benzimidazole related structural leads with improved anticancer activity, several new benzimidazole derivatives (5a-i) with 1,3,4-oxadiazole scaffold incorporated were synthesized and studied for their anticancer activity. The anticancer screening against MDA-MB-231 breast cancer cell lines showed that compound (5c) exhibited moderate cytotoxicity.

  8. Synthesis, structural and electrochemical characterization of benzimidazole compounds exhibiting a smectic C liquid crystal phase (United States)

    Wei, Bingzhuo; Tan, Shuai; Liang, Ting; Cao, Siyu; Wu, Yong


    Mesomorphic benzimidazole compounds were prepared from a biphenyl benzoate based precursor by substitution reaction of alkyl bromide with 2-mercaptobenzimidazole. Molecular structures of the benzimidazole compounds were characterized by nuclear magnetic resonance (NMR), Fourier transform infrared (FT-IR) spectroscopy and elemental analysis. Differential scanning calorimetry (DSC) measurements and polarizing optical microscopic (POM) observations revealed that the benzimidazole compounds exhibited a thermotropic smectic C (SC) phase. Temperature dependent X-ray diffraction (XRD) patterns suggested a tilted bilayer smectic structure in which intermolecular hydrogen bonds between benzimidazole moieties formed lamellar arrangement. Electrochemical impedance spectroscopy (EIS) characterization suggested that the SC phase favored anhydrous proton conduction of the benzimidazole compounds and the proton conductivities showed an Arrhenius temperature dependence.

  9. Comprehensive Review in Current Developments of Benzimidazole-Based Medicinal Chemistry. (United States)

    Keri, Rangappa S; Hiremathad, Asha; Budagumpi, Srinivasa; Nagaraja, Bhari Mallanna


    The properties of benzimidazole and its derivatives have been studied over more than one hundred years. Benzimidazole derivatives are useful intermediates/subunits for the development of molecules of pharmaceutical or biological interest. Substituted benzimidazole derivatives have found applications in diverse therapeutic areas such as antiulcer, anticancer agents, and anthelmintic species to name just a few. This work systematically gives a comprehensive review in current developments of benzimidazole-based compounds in the whole range of medicinal chemistry as anticancer, antibacterial, antifungal, anti-inflammatory, analgesic agents, anti-HIV, antioxidant, anticonvulsant, antitubercular, antidiabetic, antileishmanial, antihistaminic, antimalarial agents, and other medicinal agents. This review will further be helpful for the researcher on the basis of substitution pattern around the nucleus with an aim to help medicinal chemists for developing an SAR on benzimidazole drugs/compounds.

  10. Synthesis of arylpyrazole linked benzimidazole conjugates as potential microtubule disruptors. (United States)

    Kamal, Ahmed; Shaik, Anver Basha; Polepalli, Sowjanya; Kumar, G Bharath; Reddy, Vangala Santhosh; Mahesh, Rasala; Garimella, Srujana; Jain, Nishant


    In an attempt to develop potent and selective anticancer agents, a series of twenty arylpyrazole linked benzimidazole conjugates (10a-t) were designed and synthesized as microtubule destabilizing agents. The joining of arylpyrazole to the benzimidazole moiety resulted in a four ring (A, B, C and D) molecular scaffold that comprises of polar heterocyclic rings in the middle associated with rotatable single bonds and substituted aryl rings placed in the opposite directions. These conjugates were evaluated for their ability to inhibit the growth of sixty cancer cell line panel of the NCI. Among these some conjugates like 10a, 10b, 10d, 10e, 10p and 10r exhibited significant growth inhibitory activity against most of the cell lines ranging from 0.3 to 13μM. Interestingly, the conjugate 10b with methoxy group on D-ring expressed appreciable cytotoxic potential. A549 cells treated with some of the potent conjugates like 10a, 10b and 10d arrested cells at G2/M phase apart from activating cyclin-B1 protein levels and disrupting microtubule network. Moreover, these conjugates effectively inhibited tubulin polymerization with IC50 values of 1.3-3.8μM. Whereas, the caspase assay revealed that they activate the casepase-3 leading to apoptosis. Particularly 10b having methoxy substituent induced activity almost 3 folds higher than CA-4. Furthermore, a competitive colchicine binding assay and molecular modeling analysis suggests that these conjugates bind to the tubulin successfully at the colchicine binding site. These investigations reveal that such conjugates having pyrazole and benzimidazole moieties have the potential in the development of newer chemotherapeutic agents.

  11. Ionic conducting poly-benzimidazoles; Polybenzimidazoles conducteurs ioniques

    Energy Technology Data Exchange (ETDEWEB)

    Jouanneau, J


    Over the last years, many research works have been focused on new clean energy systems. Hydrogen fuel cell seems to be the most promising one. However, the large scale development of this technology is still limited by some key elements. One of them is the polymer electrolyte membrane 'Nafion' currently used, for which the ratio performance/cost is too low. The investigations we carried out during this thesis work are related to a new class of ionic conducting polymer, the sulfonated poly-benzimidazoles (sPBI). Poly-benzimidazoles (PBI) are aromatic heterocyclic polymers well-known for their excellent thermal and chemical stability. Ionic conduction properties are obtained by having strong acid groups (sulfonic acid SO{sub 3}H) on the macromolecular structure. For that purpose, we first synthesized sulfonated monomers. Their poly-condensation with an appropriate non-sulfonated co-monomer yields to sPBI with sulfonation range from 0 to 100 per cent. Three different sPBI structures were obtained, and verified by appropriate analytical techniques. We also showed that the protocol used for the synthesis resulted in high molecular weights polymers. We prepared ionic conducting membrane by casting sPBI solutions on glass plates. Their properties of stability, water swelling and ionic conductivity were investigated. Surprisingly, the behaviour of sPBI was quite different from the other sulfonated aromatic polymers with same amount of SO{sub 3}H, their stability was much higher, but their water swelling and ionic conductivity were quite low. We attributed these differences to strong ionic interactions between the sulfonic acid groups and the basic benzimidazole groups of our polymers. However, we managed to solve this problem synthesizing very highly sulfonated PBI, obtaining membranes with a good balance between all the properties necessary. (author)

  12. 1-[2,2-Bis(1,3-benzimidazol-1-ylmethyl-3-bromopropyl]-1,3-benzimidazole

    Directory of Open Access Journals (Sweden)

    Tai-Bao Wei


    Full Text Available The title compound, C26H23BrN6, has been synthesized as a potential ligand for the construction of metal–organic frameworks. The three benzimidazolyl groups present three potential coordination nodes. The dihedral angles between the benzimidazole ring systems are 74.03 (10, 66.49 (9 and 74.09 (9°. The structure contains large voids, which contain highly disordered solvent molecules that may be CH3CH2OH. Since the solvent molecules could not be located, the PLATON/SQUEEZE procedure [Spek (2009. Acta Cryst. D65, 148–155] was used.

  13. New benzimidazole-2-urea derivates as tubulin inhibitors. (United States)

    Wang, Wenna; Kong, Dexin; Cheng, Huimin; Tan, Li; Zhang, Zhang; Zhuang, Xiaoxi; Long, Huoyou; Zhou, Yang; Xu, Yong; Yang, Xiaohong; Ding, Ke


    Emerging drug resistance and other drawbacks limit tubulin inhibitors' therapeutic applications and developing novel tubulin inhibitors still attracts intensive efforts. We describe the discovery and structure-activity relationship study of a series of benzimidazole-2-urea derivatives as novel β tubulin inhibitors. The representative compound 6o potently suppressed the proliferation of a panel of human cancer cells (NCI-H460, Colo205, K562, A431, HepG2, Hela, MDA-MB-435S) with IC50 values of 0.040, 0.050, 0.006, 0.026, 1.774, 0.452 and 0.052 μM, respectively. Compound 6o obviously inhibited NCI-H460 spindles formation and induced cell cycle arrest at G2/M phase at 0.10 μM. Computational study suggested that 6o interacts with β tubulin in a novel binding mode. Our results suggested that benzimidazole-2-urea derivatives might be promising tubulin inhibitors with novel binding mode for further development.

  14. Molecular mechanism of resistance of Fusarium fujikuroi to benzimidazole fungicides. (United States)

    Chen, Zihao; Gao, Tao; Liang, Shuping; Liu, Kexue; Zhou, Mingguo; Chen, Changjun


    Although carbendazim (MBC) and other benzimidazole fungicides have effectively controlled bakanae disease of rice (which is caused by Fusarium fujikuroi, F. proliferatum, and F. verticillioides) in the past, MBC resistance has become common. Previous research has shown that MBC resistance results from a mutation in the β1 -tubulin (β1 tub) gene in F. verticillioides. However, MBC resistance in F. fujikuroi, a predominant species in China, does not result from a mutation in the β1 tub. The molecular mechanism of F. fujikuroi resistance against benzimidazole fungicides is poorly understood. In this study, we determined that although β1 tub and β2 -tubulin (β2 tub) in F. fujikuroi have high homology with β1 tub and β2 tub in F. verticillioides, MBC resistance in F. fujikuroi results from mutations in β2 tub [GAG(Glu)→GTG(Val) at codon 198, TTC(Phe)→TAC(Tyr) at codon 200, and GGC(Gly)→GGT(Gly) at codon 235] but not in β1 tub. Δβ2 tub (β2 tub deletion) mutants were highly sensitive to MBC, produced fewer conidia and were less virulent than parental strains. Complementation of the Δβ2 tub mutants with a copy of the whole β2 tub locus from their parental strains restored the level of MBC resistance (or sensitivity) to that of the parental strain.

  15. Syntheses of Binuclear Copper(Ⅰ)Complexes Containing Benzimidazole

    Institute of Scientific and Technical Information of China (English)

    LIU Ying-Fan; ZHAO Dong; GUO Li-Bing; ZHENG Xin; SUN Yu-An


    A binuclear copper(Ⅰ) complex [Cu2(dppm)2(C7H6N2)2](NO3)2 (C7H6N2 = benzimidazole, dppm = Ph2PCH2PPh2) has been synthesized and characterized by X-ray crystallography.The crystal belongs to monoclinic, space group C2/c with a = 14.167(3), b = 21.209(4), c =20.680(4) A, β = 103.93(3)°, C32H28CuN3O3P2, Mr = 628.05, Z = 8,μ = 0.868 mm-1, V = 6031 (2)(。A)3,F(000) = 2592, Dc= 1.383 g/cm3, R = 0.0593 and wR = 0.1736.A total of 5297 independent reflec tions were collected, of which 3503 were observed with I > 2σ(I).The central copper atom is tri-coordinated by phosphorus atoms from bridging dppm and nitrogen atom from benzimidazole.In the coordination sphere, the bond lengths of Cu-P(1) and Cu-P(2) are 2.2607(17) and 2.2503(16)(。A),respectively and the P-Cu-P bond angle is 127.26(6)°.

  16. Transport of anthelmintic benzimidazole drugs by breast cancer resistance protein (BCRP/ABCG2)

    NARCIS (Netherlands)

    Merino, G; Jonker, JW; Wagenaar, E; Pulido, MM; Molina, AJ; Alvarez, AI; Schinkel, AH


    Methylcarbamate benzimidazoles [albendazole (ABZ), fenbendazole (FBZ), and their respective sulfoxide derivatives, albendazole sulfoxide (ABZSO) and oxfendazole (OXF)] are therapeutically important anthelmintic agents with low bioavailability. We studied their in vitro interaction with the apical AT

  17. Multistep divergent synthesis of benzimidazole linked benzoxazole/benzothiazole via copper catalyzed domino annulation. (United States)

    Liao, Jen-Yu; Selvaraju, Manikandan; Chen, Chih-Hau; Sun, Chung-Ming


    An efficient, facile synthesis of structurally diverse benzimidazole integrated benzoxazole and benzothiazoles has been developed. In a multi-step synthetic sequence, 4-fluoro-3-nitrobenzoic acid was converted into benzimidazole bis-heterocycles, via the intermediacy of benzimidazole linked ortho-chloro amines. The amphiphilic reactivity of this intermediate was designed to achieve the title compounds by the reaction of various acid chlorides and isothiocyanates in a single step through the in situ formation of ortho-chloro anilides and thioureas under microwave irradiation. A versatile one pot domino annulation reaction was developed to involve the reaction of benzimidazole linked ortho-chloro amines with acid chlorides and isothiocyanates. The initial acylation and urea formation followed by copper catalyzed intramolecular C-O and C-S cross coupling reactions furnished the angularly oriented bis-heterocycles which bear a close resemblance to the streptomyces antibiotic UK-1.

  18. Ruthenium complexes containing bis-benzimidazole derivatives as a new class of apoptosis inducers. (United States)

    Li, Linlin; Wong, Yum-Shing; Chen, Tianfeng; Fan, Cundong; Zheng, Wenjie


    A series of ruthenium complexes containing bis-benzimidazole derivatives have been synthesized and identified as able to target mitochondria and induce caspase-dependent apoptosis in cancer cells through superoxide overproduction.

  19. Synthesis and in vitro antitumor evaluation of primary amine substituted quinazoline linked benzimidazole. (United States)

    Paul, Kamaldeep; Sharma, Alka; Luxami, Vijay


    By combining the structural features of quinazoline and benzimidazole, new hybrid regioisomeric molecules with substituted primary amines have been synthesized. Evaluation of these molecules over 60 cancer cell line panel has identified three molecules as most potent anticancer agents. Compound 10 showed ten and eleven folds more activity than respective quinazoline and benzimidazole class of compounds with GI50 value of 1.64 μM. Compound 11 (GI50 value of 0.81 μM) showed almost twenty and twenty-two fold more activity than quinazoline and benzimidazole analogue, respectively while compound 12 (GI50 value of 4.52 μM) has four fold more activity than quinazoline and benzimidazole analogue. In vitro evaluation of compound 11 exhibited remarkable anticancer activity towards colon cancer cell lines and prostate cancer cell lines at five dose concentrations with GI50 values of 0.34 and 0.31 μM, respectively.

  20. Efficient Syntheses of 2-Substituted Benzimidazoles and Benzoxazoles from β-Keto Esters

    Institute of Scientific and Technical Information of China (English)

    XIAO Li-wei; ZHANG Min; SUN Wen-hua


    An efficient synthetic method was developed to synthesize 2-substituted benzimidazoles and benzoxazoles withβ-keto esters as starting materials under mild reaction conditions, during which other functional groups are bearable from reactants to products.

  1. Synthesis, Characterization and Chelating Properties of Benzimidazole-Salicylic Acid Combined Molecule

    Directory of Open Access Journals (Sweden)

    Kamlesh V. Patel


    Full Text Available Aminomethylation (i.e. Mannich reaction of benzimidazole was carried out by treating benzimidalzole with formaldehyde and 4-aminosalicylic acid. The resultant compound was designated as 1-(4-carboxy-3-hydroxyphenyl aminomethyl benzimidazole (BI-SA. The transition metal complexes of Cu2+, Co2+, Ni2+, Mn2+, Zn2+ and Fe3+ of BI-SA have been prepared and characterized by elemental analyses, spectral studies, magnetic moment determination, molar conductivity measurement and microbicidal activity.

  2. Polyethylene glycol: A recyclable solvent system for the synthesis of benzimidazole derivatives using CAN as catalyst

    Indian Academy of Sciences (India)

    Mazaahir Kidwai; Anwar Jahan; Divya Bhatnagar


    Ceric ammonium nitrate (CAN) efficiently catalysed the synthesis of benzimidazole derivatives from -phenylenediamine and aldehydes in PEG. This method provides a novel route for the synthesis of benzimidazoles in good yields with little catalyst loading. The recovery and the successful reutilization of the solvent system are also presented. Moreover, the easy set-up and purification tasks of this sustainable method make it appealing for bulk industry applications.

  3. Crystal structure of a complex of human chymase with its benzimidazole derived inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Yoshiyuki; Kakuda, Shinji; Koizumi, Masahiro; Mizuno, Tsuyoshi; Muroga, Yumiko; Kawamura, Takashi; Takimoto-Kamimura, Midori, E-mail: [Teijin Institute for Bio-medical Research, 4-3-2 Asahigaoka, Hino, Tokyo 191-8512 (Japan)


    The crystal structure of human chymase complexed with a novel benzimidazole inhibitor, TJK002, was determined at 2.8 Å resolution. The present study shows that the benzimidazole ring of the inhibitor takes the stable stacking interaction with the protonated His57 in the catalytic domain of human chymase. The crystal structure of human chymase complexed with a novel benzimidazole inhibitor, TJK002, was determined at 2.8 Å resolution. The X-ray crystallographic study shows that the benzimidazole inhibitor forms a non-covalent interaction with the catalytic domain of human chymase. The hydrophobic fragment of the inhibitor occupies the S1 pocket. The carboxylic acid group of the inhibitor forms hydrogen bonds with the imidazole N(∊) atom of His57 and/or the O(γ) atom of Ser195 which are members of the catalytic triad. This imidazole ring of His57 induces π–π stacking to the benzene ring of the benzimidazole scaffold as P2 moiety. Fragment molecular orbital calculation of the atomic coordinates by X-ray crystallography shows that this imidazole ring of His57 could be protonated with the carboxyl group of Asp102 or hydroxyl group of Ser195 and the stacking interaction is stabilized. A new drug design strategy is proposed where the stacking to the protonated imidazole of the drug target protein with the benzimidazole scaffold inhibitor causes unpredicted potent inhibitory activity for some enzymes.

  4. Anti-proliferation effects of benzimidazole derivatives on HCT-116 colon cancer and MCF-7 breast cancer cell lines. (United States)

    Al-Douh, Mohammed Hadi; Sahib, Hayder B; Osman, Hasnah; Abd Hamid, Shafida; Salhimi, Salizawati M


    Benzimidazoles 1-4 were obtained using modified synthesis methods and studied for their ability to inhibit cell proliferation of colon cancer cell HCT-116 and breast cancer cell MCF-7 using MTT assays. In the HCT-116 cell line, benzimidazole 2 was found to have an IC50 value of 16.2 ± 3.85 μg/mL and benzimidazole 1 a value of 28.5 ± 2.91 μg/mL, while that for benzimidazole 4 was 24.08 ± 0.31 μg/mL. In the MCF-7 cell line, benzimidazole 4 had an IC50 value of 8.86 ± 1.10 μg/mL, benzimidazole 2 a value of 30.29 ± 6.39 μg/mL, and benzimidazole 1 a value of 31.2 ± 4.49 μg/mL. Benzimidazole 3 exerted no cytotoxicity in either of the cell lines, with IC50 values >50 μg/mL. The results suggest that benzimidazoles derivatives may have chemotherapeutic potential for treatment of both colon and breast cancers.

  5. Molecular design of synthetic benzimidazoles for the switchover of the duplex to G-quadruplex DNA recognition. (United States)

    Maji, Basudeb; Bhattacharya, Santanu


    Benzimidazole derivatives are well known for their antibacterial, antiviral, anticonvulsant, antihistaminic, anthelmintic and antidepressant activities. Benzimidazole's unique base-selective DNA recognition property has been studied widely. However, most of the early benzimidazole systems have been targeted towards the binding of duplex DNA. Here we have shown the evolution and progress of the design and synthesis of new benzimidazole systems towards selective recognition of the double-stranded DNA first. Then in order to achieve selective recognition of the G-quadruplex DNA and utilize their potential as future anti-cancer drug candidates, we have demonstrated their selective cytotoxicity towards the cancer cells and potent telomerase inhibition ability.

  6. Synthesis of Some New Benzimidazole Derivatives of Pharmaceutical Interest

    Directory of Open Access Journals (Sweden)

    Fawzia Zakaria El-Ablack


    Full Text Available Reaction of 2-(aminomethylbenzimidazole dihydrochloride (1 with ethyl acetoacetate was studied to give diazepinone-benzimidazole derivative (2, while, treatment of 1 with phenylhydrazono ethylacetoacetate afforded phenylhydrazino diazepinone derivative (3. On the other hand, reaction of 1 with acetyl acetone resulted in the formation of diazepine derivative (4. The reaction of 1 with ethyl cyanoacetate was studied to give 3-aminodiazepinone derivative (5. Also the reaction of 1 with acetophenone and/or benzophenone has been investigated to give the fused imidazolines 6 and 7 respectively, while the reaction of 1 with cyclopentanone gave benzimidazolyl derivative (8. Treatment of 1 with chloroacetyl chloride gave the fused pyrazinone (9. The treatment of 1 with benzoin gave the derivative (10. The structures of the hitherto unknown compounds have been confirmed from analytical and spectral data. The newly synthesized compounds were screened for antibacterial and antifungal activity.

  7. Antituberculosis: Synthesis and Antimycobacterial Activity of Novel Benzimidazole Derivatives

    Directory of Open Access Journals (Sweden)

    Yeong Keng Yoon


    Full Text Available A total of seven novel benzimidazoles were synthesized by a 4-step reaction starting from 4-fluoro-3-nitrobenzoic acid under relatively mild reaction conditions. The synthesized compounds were screened for their antimycobacterial activity against M. tuberculosis H37Rv (MTB-H37Rv and INH-resistant M. tuberculosis (INHR-MTB strains using agar dilution method. Three of them displayed good activity with MIC of less than 0.2 μM. Compound ethyl 1-(2-(4-(4-(ethoxycarbonyl-2-aminophenylpiperazin-1-ylethyl-2-(4-(5-(4-fluorophenylpyridin-3-ylphenyl-1H-benzo[d]imidazole-5-carboxylate (5g was found to be the most active with MIC of 0.112 μM against MTB-H37Rv and 6.12 μM against INHR-MTB, respectively.


    Directory of Open Access Journals (Sweden)



    Full Text Available A quantitative structure-activity relationship (QSAR study has been carried out for a training set of 12 benzimidazole derivatives to correlate and predict the antibacterial activity of studied compounds against Gram-negative bacteria Pseudomonas aeruginosa. Multiple linear regression was used to select the descriptors and to generate the best prediction model that relates the structural features to inhibitory activity. The predictivity of the model was estimated by cross-validation with the leave-one-out method. Our results suggest a QSAR model based on the following descriptors: parameter of lipophilicity (logP and hydration energy (HE. Good agreement between experimental and predicted inhibitory values, obtained in the validation procedure, indicated the good quality of the generated QSAR model.

  9. Anticancer activity of new compounds using benzimidazole as a scaffold. (United States)

    Rashid, Mohd; Husain, Asif; Shaharyar, Mohammad; Sarafroz, Mohd


    The design and synthesis of substituted 1-(1-ethy-1H-benzimidazol-2-yl) ethanone (3a-f) and substituted 1-(2-bromoethyl)-2- (1-hydrazinylidene or ethylidene)-1H-benzimidazole (3g-j) have been successfully achieved under microwave irradiation with an aim for finding promising anticancer agents. Among the synthetic compounds, those with potential activity were selected and evaluated in-vitro for anticancer activity at the National Cancer Institute (NCI), USA, against 60 cancer cell lines from nine types of human cancer. The title compound 3e (NSC: 765733/1) exhibited notable growth inhibition that satisfies threshold criteria at single dose (10 µM) on all human cell lines of NCI. This compound was considered for further study at five dose levels (0.01, 0.1, 1, 10 and 100 µM) with GI50 values ranging from 0.19 to 92.7 µM. Compound 3e was found superior for Non-small cell lung cancer cell lines (HOP-92) and calculated end points (GI50 0.19, TGI 1.45, LC50 >100 and Log10GI50 -6.70, Log10TGI -5.84, Log10LC50 >-4.00). Docking study was performed using Maestro 9.0 to provide binding mode into binding sites of topoisomerase enzyme (PDB ID: 1SC7). Hopefully in the future, compound 3e could be used as novel template for the development of potential anticancer agents.

  10. Effect of the physicochemical parameters of benzimidazole molecules on their retention by a nonpolar sorbent from an aqueous acetonitrile solution (United States)

    Shafigulin, R. V.; Safonova, I. A.; Bulanova, A. V.


    The effect of the structure of benzimidazoles on their chromatographic retention on octadecyl silica gel from an aqueous acetonitrile eluent was studied. One- and many-parameter correlation equations were obtained by linear regression analysis, and their prognostic potential in determining the retention factors of benzimidazoles under study was analyzed.

  11. Benzimidazole Carbamate Residues in Milk: Detection by SPR Biosensor; using a Modified QuEChERS Method for Extraction (United States)

    A surface plasmon resonance (SPR) biosensor screening assay was developed and validated to detect 11 benzimidazole carbamate (BZT) veterinary drug residues in milk. The polyclonal antibody used was raised in sheep against a methyl 5 (6)-[(carboxypentyl)-thio]-2-benzimidazole carbamate protein conjug...

  12. Penta-substituted benzimidazoles as potent antagonists of the calcium-sensing receptor (CaSR-antagonists). (United States)

    Gerspacher, Marc; Altmann, Eva; Beerli, René; Buhl, Thomas; Endres, Ralf; Gamse, Rainer; Kameni-Tcheudji, Jacques; Kneissel, Michaela; Krawinkler, Karl Heinz; Missbach, Martin; Schmidt, Alfred; Seuwen, Klaus; Weiler, Sven; Widler, Leo


    A series of novel benzimidazole derivatives has been designed via a scaffold morphing approach based on known calcilytics chemotypes. Subsequent lead optimisation led to the discovery of penta-substituted benzimidazoles that exhibit attractive in vitro and in vivo calcium-sensing receptor (CaSR) inhibitory profiles. In addition, synthesis and structure-activity relationship data are provided.

  13. Synthesis of novel polybrominated benzimidazole derivatives-potential CK2 inhibitors with anticancer and proapoptotic activity. (United States)

    Łukowska-Chojnacka, Edyta; Wińska, Patrycja; Wielechowska, Monika; Poprzeczko, Martyna; Bretner, Maria


    The efficient method for the synthesis of novel cell permeable inhibitors of protein kinase CK2 with anticancer and proapoptotic activity has been developed. A series of polybrominated benzimiadazole derivatives substituted by various cyanoalkyl groups have been synthesized. Cyanoethyl derivatives were obtained by Michael type addition of 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi) and 4,5,6,7-tetrabromo-2-methyl-1H-benzimidazole to acrylonitrile, whilst cyanomethyl, cyanopropyl and cyanobutyl analogs by N-alkylation of 4,5,6,7-tetrabromo-1H-benzimidazole and 4,5,6,7-tetrabromo-2-methyl-1H-benzimidazole with appropriate cyanoalkyl halides. The inhibitory activity against protein kinase rhCK2α catalytic subunit and cytotoxicity against two human cancer cell lines: acute lymphocytic leukemia (CCRF-CEM) and breast (MCF-7) were evaluated for all newly synthesized compounds. Additionally, the proapoptotic activity toward leukemia cells and intracellular inhibition of CK2 for the most cytotoxic derivatives have been performed, demonstrating 4,5,6,7-tetrabromo-2-methyl-1H-benzimidazole as a new selective inhibitor of rhCK2 with twenty-fold better proapoptotic activity than parental compound (TBBi).

  14. Synthesis and docking studies of novel antitumor benzimidazoles. (United States)

    Omar, Mohamed A; Shaker, Yasser M; Galal, Shadia A; Ali, Mamdouh M; Kerwin, Sean M; Li, Jing; Tokuda, Harukuni; Ramadan, Raghda A; El Diwani, Hoda I


    In this work, the benzimidazole-pyrrole conjugates 6a-h and benzimidazole-tetracycles conjugates 12-14 were prepared. The cytotoxicity of the compounds 3, 4a-h, 6a-h, 8, 10 and 12-14 was tested against lung cancer cell line A549. Compound 6b exhibited higher activity than the bis-benzoxazole natural product (UK-1), the standard. The tested 4g,h, 6a-h, 10 and 12-14 exhibited remarkable cytotoxicity activity against breast cancer cell line MCF-7 with higher activity than tamoxifen. Furthermore, compound 4h was found to be also more potent than doxurubicin. The antitumor promotion activity of synthesized compounds 4g,h, 6a-h, 10 and 12-14 has been estimated by studying their possible inhibitory effects on EBV-EA activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Among the studied compounds, the inhibitory activities of compounds 8, 13 and 14 demonstrated strong inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation without showing any cytotoxicity on the Raji cells and their effects being stronger than that of a representative control, oleanolic acid. Moreover, the molecular docking of the new compounds into plasminogen activator (uPA) receptor has been in correlation with the antitumor activity. All synthesized compounds 3, 4a-h, 6a-h, 8, 10 and 12-14 were docked into same groove of the binding site of the native co-crystalized (4-iodobenzo[b]thiophene-2-carboxamidine) ligand (PDB code:1c5x) for activity explaination. Compounds 4h, 6b and 13, giving the best docking results, were further studied to estimate their effect on the level of uPA using AssayMax human urokinase (uPA) ELISA kit. In case of A549 cell line, compound 6 exhibited similar activity to MMC, and for MCF-7 cell line, compound 4h exhibited similar activity to doxorubicin, in inhibiting the expression of uPA.

  15. Synthesis, single crystal and antitumor activities of benzimidazole-quinazoline hybrids. (United States)

    Sharma, Alka; Luxami, Vijay; Paul, Kamaldeep


    A series of novel regioisomeric hybrids of quinazoline/benzimidazole viz. (3-allyl-2-methyl-3H-benzimidazol-5-yl)-(2-substituted-quinazolin-4-yl)-amine and (1-allyl-2-methyl-1H-benzimidazol-5-yl)-(2-substituted-quinazolin-4-yl)-amine of biological interest were synthesized. All the synthesized compounds were well characterized by (1)H and (13)C NMR as well as mass spectroscopy. The newly synthesized compounds were screened for in vitro antitumor activities against 60 tumor cell lines panel assay. A significant inhibition for cancer cells were observed with compound 9 and also more active against known drug 5-fluorouracil (5-FU) in some tumor cell lines. Compound 9 displayed appreciable anticancer activity against leukemia, colon, melanoma, renal and breast cancer cell lines.

  16. Polybenzimidazole Membranes Containing Benzimidazole Side Groups for High Temprature Polymer Electrolyte Membrane Fuel Cells

    DEFF Research Database (Denmark)

    Yang, Jingshuai; Li, Xueyuan; Xu, Yizin


    Polybenzimidazole (PBI) with a high molecular weight of 69,000 was first synthesized. It was afterwards grafted with benzimidazole pendant groups on the backbones. The acid doped benzimidaozle grafted PBI membranes were investigated and characterized including fuel cell tests at elevated temperat......Polybenzimidazole (PBI) with a high molecular weight of 69,000 was first synthesized. It was afterwards grafted with benzimidazole pendant groups on the backbones. The acid doped benzimidaozle grafted PBI membranes were investigated and characterized including fuel cell tests at elevated...... temperatures without humidification. At an acid doping level of 13.1 mol H3PO4 per average molar repeat unit, the PBI membranes with a benzimidazole grafting degree of 10.6% demonstrated a conductivity of 0.15 S cm-1 and a H2-air fuel cell peak power density of 378 mW cm-2 at 180 oC at ambient pressure without...

  17. Crystal structures and intermolecular interactions of two novel antioxidant triazolyl-benzimidazole compounds

    Energy Technology Data Exchange (ETDEWEB)

    Karayel, A., E-mail:, E-mail:; Özbey, S. [Hacettepe University, Physics Engineering Department (Turkey); Ayhan-Kılcıgil, G.; Kuş, C. [Ankara University, Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Turkey)


    The crystal structures of 5-(2-(p-chlorophenylbenzimidazol-1-yl-methyl)-4-(3-fluorophenyl)-2, 4-dihydro-[1,2,4]-triazole-3-thione (G6C) and 5-(2-(p-chlorophenylbenzimidazol-1-yl-methyl)-4-(2-methylphenyl)-2, 4-dihydro-[1,2,4]-triazole-3-thione (G4C) have been determined by single-crystal X-ray diffraction. Benzimidazole ring systems in both molecules are planar. The triazole part is almost perpendicular to the phenyl and the benzimidazole parts of the molecules in order to avoid steric interactions between the rings. The crystal structures are stabilized by intermolecular hydrogen bonds between the amino group of the triazole and the nitrogen atom of benzimidazole of a neighboring molecule.

  18. JVG9, a benzimidazole derivative, alters the surface and cytoskeleton of Trypanosoma cruzi bloodstream trypomastigotes (United States)

    Díaz-Chiguer, Dylan L; Hernández-Luis, Francisco; Nogueda-Torres, Benjamín; Castillo, Rafael; Reynoso-Ducoing, Olivia; Hernández-Campos, Alicia; Ambrosio, Javier R


    Trypanosoma cruzi has a particular cytoskeleton that consists of a subpellicular network of microtubules and actin microfilaments. Therefore, it is an excellent target for the development of new anti-parasitic drugs. Benzimidazole 2-carbamates, a class of well-known broad-spectrum anthelmintics, have been shown to inhibit the in vitro growth of many protozoa. Therefore, to find efficient anti-trypanosomal (trypanocidal) drugs, our group has designed and synthesised several benzimidazole derivatives. One, named JVG9 (5-chloro-1H-benzimidazole-2-thiol), has been found to be effective against T. cruzi bloodstream trypomastigotes under both in vitro and in vivo conditions. Here, we present the in vitro effects observed by laser scanning confocal and scanning electron microscopy on T. cruzi trypomastigotes. Changes in the surface and the distribution of the cytoskeletal proteins are consistent with the hypothesis that the trypanocidal activity of JVG9 involves the cytoskeleton as a target. PMID:25317703

  19. Genetic basis of benzimidazole resistance in Teladorsagia circumcincta in Ireland. (United States)

    Keegan, Jason D; Good, Barbara; de Waal, Theo; Fanning, June; Keane, Orla M


    Resistance to benzimidazole (BZ) anthelmintics is common in ovine nematodes of economic importance. Single nucleotide polymorphisms (SNP) at three positions in the isotype 1 β- tubulin gene have been associated with BZ resistance and molecular tests for the detection of BZ resistance have been developed. In order to determine if such tests are practicable in Ireland the polymorphisms associated with BZ resistance must be identified. To this end, BZ-resistant nematodes were recovered from four farms in Ireland. Resistant Teladorsagia circumcincta, Cooperia curticei and Trichostrongylus colubriformis were recovered, with resistant T. circumcincta the most common and the only species studied further. Sequencing of the isotype 1 β-tubulin gene from resistant T. circumcincta identified a T - A transition, resulting in an F200Y substitution known to be responsible for BZ-resistance, on three of the farms. However, on the fourth farm the frequency of the resistant A allele was only 0.33 indicating another BZ resistance mechanism may be present on this farm. An additional polymorphism resulting in a substitution of glutamate for leucine (E198L) was also found on this farm at low frequency (0.17). No polymorphisms at position 167 were identified on any farm. Therefore, molecular tests to detect BZ resistance in T. circumcincta in Ireland could prove useful; however, they may result in some instances of resistance remaining undetected.

  20. Biological Activity and Molecular Structures of Bis(benzimidazole and Trithiocyanurate Complexes

    Directory of Open Access Journals (Sweden)

    Pavel Kopel


    Full Text Available 1-(1H-Benzimidazol-2-yl-N-(1H-benzimidazol-2-ylmethylmethanamine (abb and 2-(1H-benzimidazol-2-ylmethylsulfanylmethyl-1H-benzimidazole (tbb have been prepared and characterized by elemental analysis. These bis(benzimidazoles have been further used in combination with trithiocyanuric acid for the preparation of complexes. The crystal and molecular structures of two of them have been solved. Each nickel atom in the structure of trinuclear complex [Ni3(abb3(H2O3(μ-ttc](ClO43·3H2O·EtOH (1, where ttcH3 = trithiocyanuric acid, is coordinated with three N atoms of abb, the N,S donor set of ttc anion and an oxygen of a water molecule. The crystal of [(tbbH2(ttcH22(ttcH3(H2O] (2 is composed of a protonated bis(benzimidazole, two ttcH2 anions, ttcH3 and water. The structure is stabilized by a network of hydrogen bonds. These compounds were primarily synthesized for their potential antimicrobial activity and hence their possible use in the treatment of infections caused by bacteria or yeasts (fungi. The antimicrobial and antifungal activity of the prepared compounds have been evaluated on a wide spectrum of bacterial and yeast strains and clinical specimens isolated from patients with infectious wounds and the best antimicrobial properties were observed in strains after the use of ligand abb and complex 1, when at least 80% growth inhibition was achieved.

  1. Synthesis, antimicrobial and cytotoxic activities of pyrimidinyl benzoxazole, benzothiazole and benzimidazole. (United States)

    Seenaiah, D; Reddy, P Ramachandra; Reddy, G Mallikarjuna; Padmaja, A; Padmavathi, V; Krishna, N Siva


    A variety of pyrimidinyl benzoxazoles, benzothiazoles and benzimidazoles linked by thio, methylthio and amino moieties were prepared and studied their antimicrobial and cytotoxic activities. The compound pyrimidinyl bis methylthio benzimidazole 22 was a potent antimicrobial agent particularly against Staphylococcus aureus (29 mm, MIC 12.5 μg/mL) and Penicillium chrysogenum (38 mm, MIC 12.5 μg/mL). The amino linked pyrimidinyl bis benzothiazole 24 exhibited cytotoxic activity on A549 cells with IC50 value of 10.5 μM.

  2. Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors. (United States)

    Lee, Kyeong; Goo, Ja-Il; Jung, Hwa Young; Kim, Minkyoung; Boovanahalli, Shanthaveerappa K; Park, Hye Ran; Kim, Mun-Ock; Kim, Dong-Hyun; Lee, Hyun Sun; Choi, Yongseok


    A novel series of benzimidazole derivatives was prepared and evaluated for their diacylglycerol acyltransferase (DGAT) inhibitory activity using microsome from rat liver. Among the newly synthesized compounds, furfurylamine containing benzimidazole carboxamide 10j showed the most potent DGAT inhibitory effect (IC(50)=4.4 μM) and inhibited triglyceride formation in HepG2 cells. Furthermore, compound 10j reduced body weight gain of Institute of Cancer Research mice on a high-fat diet and decreased levels of total triglyceride, total cholesterol, and LDL-cholesterol in the blood accompanied with a significant increase in HDL-cholesterol level.

  3. Structure-activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH (United States)

    Kirubakaran, Sivapriya; Gorla, Suresh Kumar; Sharling, Lisa; Zhang, Minjia; Liu, Xiaoping; Ray, Soumya S.; MacPherson, Iain S.; Striepen, Boris; Hedstrom, Lizbeth; Cuny, Gregory D.


    Cryptosporidium parasites are important waterborne pathogens of both humans and animals. The C. parvum and C. hominis genomes indicate that the only route to guanine nucleotides is via inosine 5'-monophosphate dehydrogenase (IMPDH). Thus the inhibition of the parasite IMPDH presents a potential strategy for treating Cryptosporidium infections. A selective benzimidazole-based inhibitor of C. parvum IMPDH (CpIMPDH) was previously identified in a high throughput screen. Here we report a structure-activity relationship study of benzimidazole-based compounds that resulted in potent and selective inhibitors of CpIMPDH. Several compounds display potent antiparasitic activity in vitro. PMID:22310229

  4. Regioselective Synthesis of Some Pyrazole Scaffolds Attached to Benzothiazole and Benzimidazole Moieties

    Directory of Open Access Journals (Sweden)

    Nabila A. Kheder


    Full Text Available Condensation of 2-(benzothiazol-2-ylacetonitrile (1 or 2-(1-methyl-1H-benzimidazol-2-ylacetonitrile (2 with thiophene-2-carbaldehyde afforded the corresponding acrylonitrile derivatives 3 or 4, respectively. The 1,3-dipolar cycloaddition reaction of the acrylonitrile 3 or 4 with nitrile-imine 6 gave novel pyrazole derivatives pendant to benzothiazole and benzimidazole. The pyrazoline derivative 7 was converted into the corresponding pyrazole derivative 11 via thermal elimination of hydrogen cyanide upon heating in sodium ethoxide solution. The structures of the synthesized products were confirmed by IR, 1H NMR, and mass spectral techniques.

  5. Benzimidazole--ibuprofen/mesalamine conjugates: potential candidates for multifactorial diseases. (United States)

    Bansal, Yogita; Kaur, Maninder; Silakari, Om


    Ibuprofen (IB) and mesalamine (MES) are commonly used NSAIDs whereas benzimidazole (BZ) and 2-aminobenzimidazole (ABZ) are important pharmacophore for immunomodulatory activities. In the present study, IB and MES were coupled with variedly substituted BZ or ABZ nucleus to synthesize IB-BZ (2a-2e), IB-ABZ (3a-3e), MES-BZ (4a-4e) and MES-ABZ (5a-5e) chimeric conjugates as novel compounds that could elicit both anti-inflammatory and immunomodulatory activities. Each compound retained the anti-inflammatory activity of the parent NSAID. The BZ conjugates (2 and 4) were found immunostimulatory whereas the ABZ conjugates (3 and 5) were immunosuppressive. Each compound also exhibited good antioxidant activity, which is attributed to the electron rich BZ and ABZ nuclei. Compound 2a, 2e, 3a, 3e and 5b exhibited the most significant anti-inflammatory and immunomodulatory activities. Hence, these were evaluated for in vivo acute gastric ulcerogenicity. The compounds were safe to gastric mucosa, probably due to masking of the free -COOH group of IB and MES, and/or to the BZ nucleus itself. A benzoyl group at 5-position of BZ and ABZ incurred maximum immunostimulatory activity. In contrast, a -NO2 group incurred the maximum immunosuppressive action. Docking analysis revealed the compounds to be more selective towards COX-2 enzyme, which support the gastroprotective activity. These results suggest that the compounds can be taken as lead for development of new drugs for the treatment of immune related inflammatory disorders, such as cancer and rheumatoid arthritis.

  6. Uptake of benzimidazoles by Trichuris suis in vivo in pigs (United States)

    Hansen, Tina V.A.; Friis, Christian; Nejsum, Peter; Olsen, Annette; Thamsborg, Stig Milan


    It is recognized that the clinical efficacy of single dose benzimidazoles (BZs) against the nematode, Trichuris suis of pigs and the closely related Trichuris trichiura in humans is only poor to moderate. Recent in vitro studies have indicated that a low uptake of fenbendazole (FBZ) in T. suis may be responsible for its poor efficacy. The aim of this study was to investigate this hypothesis by measuring the concentrations of FBZ and its metabolites, oxfendazole (OXF) and FBZ sulphone (FBZSO2), in T. suis isolated from FBZ treated pigs and in plasma of the pigs. The highest concentration of FBZ measured in T. suis was 66.6 pmol/mg dry worm tissue which was approximately half of what was measured in a previous in vitro study. The correlation between drug concentrations in plasma and in T. suis worms was highly positive for OXF (r = 0.93, P = 0.0007) and FBZSO2 (r = 0.85, P = 0.007), but no correlation was found for FBZ. This study shows that the low uptake of FBZ observed for T. suis in vitro, also takes place in vivo. The high and significant correlations between OXF and FBZSO2 concentrations in plasma of the pigs and T. suis (and the lack of this correlation for FBZ) suggests that the metabolites reach the worms via the blood–enterocyte interface while FBZ primarily reaches the worms via the intestinal lumen of the host. PMID:25057460

  7. Cytotoxic, Antiproliferative and Apoptotic Effects of New Benzimidazole Derivatives on A549 Lung Carcinoma and C6 Glioma Cell Lines. (United States)

    Yurttas, Leyla; Demirayak, Seref; Ciftci, Gulsen Akalın


    Benzimidazole ring is a versatile structure which has been extensively utilized in medicinal chemistry. Since we are working on 1,2-disubstutited benzimidazoles, we have reported new antitumor active derivatives. As a continuation to our previous work, we have synthesized a new series of 1-(2-aryl-2-oxoethyl)-2-[(N,Ndimethylamino/pyrrolidinyl/piperidinyl)thiocarbamoyl] benzimidazole derivatives. Anticancer activity of the compounds was evaluated using MTT assay, BrdU assay and flow cytometric analysis on A549 human lung carcinoma and C6 rat glioma cell lines. Compounds bearing dimethylamino moiety exhibited higher antitumor activity.

  8. Triphenylamine based benzimidazole and benzothiazole: Synthesis and applications in fluorescent chemosensors and laser dyes

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yang [State Key Laboratory of Luminescence and Applications, Changchun Institute of Optics Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033 (China); University of Chinese Academy of Sciences, Beijing 100039 (China); Li, Bin, E-mail: [State Key Laboratory of Luminescence and Applications, Changchun Institute of Optics Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033 (China); Zhang, Liming; Guan, Yunlong [State Key Laboratory of Luminescence and Applications, Changchun Institute of Optics Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033 (China)


    Triphenylamine based fluorescent dyes TPA-benzimidazole and TPA-benzothiazole have been designed and synthesized. The TPA-benzimidazole chemosensor was tested for a number of metal ions and found to exhibit binding affinity for Fe{sup 3+} and Hg{sup 2+} in acetonitrile, and the fluorescence quenching was achieved through a PET process. The appearance of an isosbestic point in absorption titrations and Job's plot analysis supported 1:1 stoichiometries for Fe{sup 3+} and Hg{sup 2+} ions. Laser experiments showed that under transversal pumping with a Q-switched Nd:YAG (355 nm) laser in toluene, TPA-benzothiazole exhibits efficient and stable amplified spontaneous emissions (ASE) at 436 nm. -- Highlights: • Triphenylamine based fluorescent dyes TPA-benzimidazole and TPA-benzothiazole have been designed and synthesized. • The TPA-benzimidazole exhibits binding affinity for Fe{sup 3+} and Hg{sup 2+} in acetonitrile and the fluorescence quenching was achieved through a PET process. • Under transversal pumping at 355 nm in toluene, TPA-benzothiazole exhibits efficient and stable amplified spontaneous emissions (ASE) in 436 nm.

  9. Synthesis and in vitro antiproliferative evaluation of some B-norcholesteryl Benzimidazole and Benzothiazole derivatives. (United States)

    Cui, Jianguo; Qi, Binbin; Gan, Chunfang; Liu, Zhipin; Huang, Hu; Lin, Qifu; Zhao, Dandan; Huang, Yanmin


    Taking orostanal (a compound from a Japanese marine sponge, Stelletta hiwasaensis) as a lead compound, some novel B-norcholesteryl benzimidazole and benzothiazole derivatives were synthesized. The antiproliferative activity of the compounds against human cervical carcinoma (HeLa), human lung carcinoma (A549), human liver carcinoma cells (HEPG2) and normal kidney epithelial cells (HEK293T) was assayed. The results revealed that the benzimidazole group was a better substituent than benzothiazole group for increasing the antiproliferative activity of compounds. 2-(3β'-Acetoxy-5β'-hydroxy-6'-B-norcholesteryl)benzimidazole (9b) with the structure of 6-benzimidazole displays the best antiproliferative activity to the cancer cells in all compounds, but is almost inactive to normal kidney epithelial cells (HEK293T). The assay of compound 9b to cancer cell apoptosis by flow cytometry showed that the compound was able to effectively induce cancer cell apoptosis. The research provided a theoretical reference for the exploration of new anti-cancer agents and may be useful for the design of novel chemotherapeutic drugs.

  10. Density functional theory molecular modeling, chemical synthesis, and antimicrobial behaviour of selected benzimidazole derivatives (United States)

    Marinescu, Maria; Tudorache, Diana Gabriela; Marton, George Iuliu; Zalaru, Christina-Marie; Popa, Marcela; Chifiriuc, Mariana-Carmen; Stavarache, Cristina-Elena; Constantinescu, Catalin


    Eco-friendly, one-pot, solvent-free synthesis of biologically active 2-substituted benzimidazoles is presented and discussed herein. Novel N-Mannich bases are synthesized from benzimidazoles, secondary amines and formaldehyde, and their structures are confirmed by 1H nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR), and elemental analysis. All benzimidazole derivatives are evaluated by qualitative and quantitative methods against 9 bacterial strains. The largest microbicide and anti-biofilm effect is observed for the 2-(1-hydroxyethyl)-compounds. Density functional theory (DFT) modeling of the molecular structure and frontier molecular orbitals, i.e. highest occupied molecular orbital and lowest unoccupied molecular orbital (HOMO/LUMO), is accomplished by using the GAMESS 2012 software. Antimicrobial activity is correlated with the electronic parameters (chemical hardness, electronic chemical potential, global electrophilicity index), Mullikan atomic charges and geometric parameters of the benzimidazole compounds. The planarity of the compound, symmetry of the molecule, and the presence of a nucleophilic group, are advantages for a high antimicrobial activity. Finally, we briefly show that further accurate processing of such compounds into thin films and hybrid structures, e.g. by laser ablation matrix-assisted pulsed laser evaporation and/or laser-induced forward transfer, may indeed provide simple and environmental friendly, state-of-the-art solutions for antimicrobial coatings.

  11. Uptake of benzimidazoles by Trichuris suis in vivo in pigs

    DEFF Research Database (Denmark)

    Hansen, Tina Vicky Alstrup; Friis, Christian; Nejsum, Peter;


    It is recognized that the clinical efficacy of single dose benzimidazoles (BZs) against the nematode, Trichuris suis of pigs and the closely related Trichuris trichiura in humans is only poor to moderate. Recent in vitro studies have indicated that a low uptake of fenbendazole (FBZ) in T. suis may...

  12. Recognition of HIV-TAR RNA using neomycin-benzimidazole conjugates. (United States)

    Ranjan, Nihar; Kumar, Sunil; Watkins, Derrick; Wang, Deyun; Appella, Daniel H; Arya, Dev P


    Synthesis of a novel class of compounds and their biophysical studies with TAR-RNA are presented. The synthesis of these compounds was achieved by conjugating neomycin, an aminoglycoside, with benzimidazoles modeled from a B-DNA minor groove binder, Hoechst 33258. The neomycin-benzimidazole conjugates have varying linkers that connect the benzimidazole and neomycin units. The linkers of varying length (5-23 atoms) in these conjugates contain one to three triazole units. The UV thermal denaturation experiments showed that the conjugates resulted in greater stabilization of the TAR-RNA than either neomycin or benzimidazole used in the synthesis of conjugates. These results were corroborated by the FID displacement and tat-TAR inhibition assays. The binding of ligands to the TAR-RNA is affected by the length and composition of the linker. Our results show that increasing the number of triazole groups and the linker length in these compounds have diminishing effect on the binding to TAR-RNA. Compounds that have shorter linker length and fewer triazole units in the linker displayed increased affinity towards the TAR RNA.

  13. Frequency of benzimidazole resistance inHaemonchus contortus populations isolated from buffalo, goat and sheep herds

    Directory of Open Access Journals (Sweden)

    Ronaldo Luiz Nunes

    Full Text Available Anthelmintic resistance is an increasing problem that threatens livestock production worldwide. Understanding of the genetic basis of benzimidazole resistance recently allowed the development of promising molecular diagnostic tools. In this study, isolates of Haemonchus contortus obtained from goats, sheep and buffaloes raised in Brazil were screened for presence of the polymorphism Phe200Tyr in the β-tubulin 1 gene, which confers resistance to benzimidazole. The allelic frequency of the mutation conferring resistance ranged from 7% to 43%, and indicated that resistance to benzimidazole could be found in nematodes isolated from all the ruminant species surveyed. Although significant variation in the frequency of the F200Y mutation was observed between different herds or host species, no significant variation could be found in populations isolated from animals within the same herd. These findings suggest that screening of samples from a few animals has the potential to provide information about the benzimidazole resistance status of the entire herd, which would enable a considerable reduction in the costs of diagnosis for the producer. Molecular diagnosis has practical advantages, since it can guide the choice of anthelmintic drug that will be used, before its application in the herd, thus reducing the economic losses driven by anthelmintic resistance.

  14. Ammonium metavanadate: A novel catalyst for synthesis of 2-substituted benzimidazole derivatives

    Institute of Scientific and Technical Information of China (English)

    Ganesh R. Jadhav; Mohammad U. Shaikh; Rajesh P. Kale; Charansingh H. Gill


    Ammonium metavanadate (10 tool%) was found to be a useful catalyst for the synthesis of various 2-substituted aryl benzimidazoles. It was used as an oxidizing agent for the condensation of o-pbenylenediamine with different substituted aryl aldehydes at room temperature in ethanol. The method was proved to be simple, convenient and the product was isolated with good yields (79-91%).

  15. Aminosilanes derived from 1H-benzimidazole-2(3H)-thione

    Energy Technology Data Exchange (ETDEWEB)

    Palomo-Molina, Juliana [Facultad de Ciencias Químicas, Universidad de Colima, Carretera Coquimatlán-Colima, Coquimatlán Colima 28400 (Mexico); García-Báez, Efrén V. [Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Avenida Acueducto s/n, Barrio La Laguna Ticomán, México DF 07340 (Mexico); Contreras, Rosalinda [Departamento de Química, Centro de Investigación y de Estudios Avanzados del IPN, Apartado Postal 14-740, México DF 07000 (Mexico); Barrio La Laguna Ticomán, México DF 07340 (Mexico); Pineda-Urbina, Kayim; Ramos-Organillo, Angel, E-mail: [Facultad de Ciencias Químicas, Universidad de Colima, Carretera Coquimatlán-Colima, Coquimatlán Colima 28400 (Mexico)


    In two trimethylsilyl-substituted 1H-benzimidazole-2(3H)-thiones, noncovalent C—H⋯π interactions between the centroid of the benzmidazole system and the SiMe{sub 3} groups form helicoidal arrangements in one, and dimerization results in the formation of R{sub s} {sup 2}(8) rings via N—H⋯S interactions, along with parallel π–π interactions between imidazole and benzene rings, in the second compound. Two new molecular structures, namely 1,3-bis(trimethylsilyl)-1H-benzimidazole-2(3H)-thione, C{sub 13}H{sub 22}N{sub 2}SSi{sub 2}, (2), and 1-trimethylsilyl-1H-benzimidazole-2(3H)-thione, C{sub 10}H{sub 14}N{sub 2}SSi, (3), are reported. Both systems were derived from 1H-benzimidazole-2(3H)-thione. Noncovalent C—H⋯π interactions between the centroid of the benzmidazole system and the SiMe{sub 3} groups form helicoidal arrangements in (2). Dimerization of (3) results in the formation of R{sub 2}{sup 2}(8) rings via N—H⋯S interactions, along with parallel π–π interactions between imidazole and benzene rings.

  16. Standardization of the egg hatch test for the detection of benzimidazole resistance in parasitic nematodes

    NARCIS (Netherlands)

    Samson-Himmelstjerna, von G.; Coles, G.; Jackson, F.; Bauer, C.; Borgsteede, F.H.M.; Cirak, V.; Demeler, J.; Donnan, A.; Dorny, P.; Epe, C.; Harder, A.; Hoglund, J.; Kaminsky, R.; Kerboeuf, D.; Kuttler, U.; Papadopoulos, E.; Posedi, J.; Small, J.; Varady, M.; Verscruysse, J.; Wirtherle, N.


    The ability to reliably detect anthelmintic resistance is a crucial part of resistance management. If data between countries are to be compared, the same test should give the same results in each laboratory. As the egg hatch test for benzimidazole resistance is used for both research and surveys, th

  17. Fixation of carbon dioxide into dimethyl carbonate over titanium-based zeolitic thiophene-benzimidazolate framework (United States)

    A titanium-based zeolitic thiophene-benzimidazolate framework has been designed for the direct synthesis of dimethyl carbonate (DMC) from methanol and carbon dioxide. The developed catalyst activates carbon dioxide and delivers over 16% yield of DMC without the use of any dehydra...

  18. High temperature fuel cell membranes based on poly(arylene ether)s containing benzimidazole groups

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dae Sik [Los Alamos National Laboratory; Kim, Yu Seung [Los Alamos National Laboratory; Lee, Kwan - Soo [Los Alamos National Laboratory; Boncella, James M [Los Alamos National Laboratory; Kuiper, David [Los Alamos National Laboratory; Guiver, Michael D [CANADA


    Development of new high-performance polymer membranes that retain their proton conductivity under low humidity conditions is one of the most critical requirements to commercialize PEMFC systems. Current sulfonated proton exchange membranes acquire proton conductivity by water that solvates ion and carries proton. Consequently, a loss of water under low RH conditions immediately results in a loss of proton conductivity. One approach to maintain proton conductivity under low RH conditions is to replace water with a less volatile proton solvent. Kreuer has pointed out the possibility to develop fully polymeric proton-conducting membranes based on nitrogen-containing heterocycles such as imidazole, benzimidazole, and pyrazole. We have attempted to blend those less volatile proton solvent with sulfonated copolymers such as polystyrene sulfonic acid, Nafion, poly(arylene ether sulfone, BPSH-xx). [Ref. DOE review meeting 2007 and 2008] However, we observed that imidazole was slowly sublimated out as temperature and humidity increases which could cause poisoning of electro-catalyst, corrosion and losing conductivity. In this presentation, we report the synthesis of novel poly(arylene ether sulfone)s containing benzimidazole groups These benzimidazole containing polymer was blended with sulfonated poly(arylene ether sulfone). In the blend system, benzimidazole group attached to the polysulfone acts as a medium through the basic nitrogen for transfer of protons between the sulfonic acid groups. Proton conductivity of the blend membranes was investigated as a function of water content at 80 C and compared the performance with water based proton conduction system.

  19. Molecular characterization, fitness and mycotoxin production of benzimidazole-resistant isolates of Penicillium expansum. (United States)

    Malandrakis, Anastasios A; Markoglou, Anastasios N; Konstantinou, Sotiris; Doukas, Eleftherios G; Kalampokis, John F; Karaoglanidis, George S


    Penicillium expansum field-strains resistant to benzimidazole fungicides were isolated in high frequency from decayed apple fruit collected from packinghouses and processing industries located in the region of Imathia, N. Greece. In vitro fungitoxicity tests resulted in the identification of two different resistant phenotypes: highly (BEN-HR) and moderately (BEN-MR) carbendazim-resistant. Thirty seven percent of the isolated P. expansum strains belonged to the BEN-HR phenotype, carried no apparent fitness penalties and exhibited resistance levels higher than 60 based on EC50 values. Cross resistance studies with other benzimidazole fungicides showed that all BEN-HR and BEN-MR isolates were also less sensitive to benomyl and thiabendazole. Fungitoxicity tests on the response of BEN-HR isolates to fungicides belonging to other chemical classes revealed no cross-resistance relationships between benzimidazoles and the phenylpyrrole fludioxonil, the dicarboximide iprodione, the anilinopyrimidine cyprodinil, the QoI pyraclostrobin, the imidazole imazalil and the triazole tebuconazole, indicating that a target-site modification is probably responsible for the BEN-HR phenotype observed. Contrary to the above, some BEN-MR isolates exhibited an increased sensitivity to cyprodinil compared to benzimidazole-sensitive ones. BEN-MR isolates had fitness parameters similar to the benzimidazole-sensitive isolates except for conidia production which appeared significantly decreased. Analysis of mycotoxin production (patulin and citrinin) showed that all benzimidazole-resistant isolates produced mycotoxins at concentrations significantly higher than sensitive isolates both on culture medium and on artificially inoculated apple fruit. Comparison of the β-tubulin gene DNA sequence between resistant and sensitive isolates revealed a point mutation resulting from the E198A substitution of the corresponding protein in most but not all HR isolates tested. Molecular analysis of the

  20. Benzimidazoles diminish ERE transcriptional activity and cell growth in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Payton-Stewart, Florastina [Department of Chemistry, College of Arts and Sciences, Xavier University of Louisiana, New Orleans, LA (United States); Tilghman, Syreeta L. [Division of Basic Pharmaceutical Sciences, College of Pharmacy, Xavier University of Louisiana, New Orleans, LA (United States); Williams, LaKeisha G. [Division of Clinical and Administrative Sciences, College of Pharmacy Xavier University of Louisiana, New Orleans, LA (United States); Winfield, Leyte L., E-mail: [Department of Chemistry, Spelman College, Atlanta, GA (United States)


    Highlights: • The methyl-substituted benzimidazole was more effective at inhibiting growth in MDA-MB 231 cells. • The naphthyl-substituted benzimidazole was more effective at inhibiting growth in MCF-7 cells than ICI. • The benzimidazole molecules demonstrated a dose-dependent reduction in ERE transcriptional activity. • The benzimidazole molecules had binding mode in ERα and ERβ comparable to that of the co-crystallized ligand. - Abstract: Estrogen receptors (ERα and ERβ) are members of the nuclear receptor superfamily. They regulate the transcription of estrogen-responsive genes and mediate numerous estrogen related diseases (i.e., fertility, osteoporosis, cancer, etc.). As such, ERs are potentially useful targets for developing therapies and diagnostic tools for hormonally responsive human breast cancers. In this work, two benzimidazole-based sulfonamides originally designed to reduce proliferation in prostate cancer, have been evaluated for their ability to modulate growth in estrogen dependent and independent cell lines (MCF-7 and MDA-MB 231) using cell viability assays. The molecules reduced growth in MCF-7 cells, but differed in their impact on the growth of MDA-MB 231 cells. Although both molecules reduced estrogen response element (ERE) transcriptional activity in a dose dependent manner, the contrasting activity in the MDA-MB-231 cells seems to suggest that the molecules may act through alternate ER-mediated pathways. Further, the methyl analog showed modest selectivity for the ERβ receptor in an ER gene expression array panel, while the naphthyl analog did not significantly alter gene expression. The molecules were docked in the ligand binding domains of the ERα-antagonist and ERβ-agonist crystal structures to evaluate the potential of the molecules to interact with the receptors. The computational analysis complimented the results obtained in the assay of transcriptional activity and gene expression suggesting that the molecules

  1. The Synthesis and Evaluation of Third-Order Optical Nonlinearities of Model Compounds Containing Benzothiazole, Benzimidazole and Benzoxazole Moieties. (United States)


    AD-A235 622 WL-TR-91-4015 THE SYNTHESIS AND EVALUATION OF THIRD-ORDER OPTICAL NONLINEARITIES OF MODEL COMPOUNDS CONTAINING BENZOTHIAZOLE ...Nonlinearities of Model Compounds Containing Benzothiazole , Benzimidazole, and Benzoxazole Moieties 12 PERSONAL AUTHOR(S) Bruce A. Reinhardt, Marilyn R...necessary and identify by block number) FIELD GROUP SUB-GROUP nonlinear optical properties benzothiazole u/ 03 degenerate four-wave mixing benzimidazole 21

  2. 1,3-Bis(3-phenylpropyl-1H-1,3-benzimidazole-2(3H-selone

    Directory of Open Access Journals (Sweden)

    Mehmet Akkurt


    Full Text Available The title molecule, C25H26N2Se, has mirror symmetry, with the mirror plane passing through the atoms of the C=Se bond and the mid-points of the two C—C bonds of the benzene ring of the benzimidazole group. The dihedral angle between the benzimidazole ring system and the phenyl ring is 71.62 (14°.

  3. 1,3-Dibenzyl-1H-benzimidazol-2(3H-one

    Directory of Open Access Journals (Sweden)

    Youssef Kandri Rodi


    Full Text Available In the molecular structure of the title compound, C21H18N2O, the fused-ring system is essentially planar, the largest deviation from the mean plane being 0.0121 (9 Å. The O atom and adjacent C atom are located in Wyckoff position 4e on a twofold axis (0, y, 1/4. The two benzyl groups are almost perpendicular to the benzimidazole plane, but point in opposite directions. The dihedral angle between the benzimidazole mean plane and the phenyl ring is 81.95 (5°, whereas that between the two benzyl groups is 60.96 (7°.

  4. Synthesis and evaluation of novel benzimidazole derivatives as sirtuin inhibitors with antitumor activities. (United States)

    Yoon, Yeong Keng; Ali, Mohamed Ashraf; Wei, Ang Chee; Choon, Tan Soo; Osman, Hasnah; Parang, Keykavous; Shirazi, Amir Nasrolahi


    A total of 15 novel benzimidazole derivatives were designed, synthesized and evaluated for their SIRT1 and SIRT2 inhibitory activity. All compounds showed better inhibition on SIRT2 as compared to SIRT1. Among these, compound 5j displayed the best inhibitory activity for SIRT1 (IC50=58.43μM) as well as for SIRT2 (IC50=45.12μM). Cell cytotoxicity assays also showed that compound 5j possesses good antitumor activity against two different cancer cell lines derived from breast cancer (MCF-7 and MDA-MB-468). A simple structure-activity-relationship (SAR) study of the newly synthesized benzimidazole derivatives was also discussed.

  5. Synthesis and biological evaluation of benzimidazole-oxindole conjugates as microtubule-targeting agents. (United States)

    Kamal, Ahmed; Nagaseshadri, B; Nayak, V Lakshma; Srinivasulu, Vunnam; Sathish, Manda; Kapure, Jeevak Sopanrao; Suresh Reddy, C


    A series of benzimidazole-oxindole conjugates were synthesized and evaluated for their cytotoxic activity. The cytotoxicity assay results suggest that conjugates 5c and 5p exhibit promising cytotoxicity against human breast cancer cell line (MCF-7). The Cell cycle analysis revealed that these conjugates induced cell cycle arrest at G2/M phase in MCF-7 cells. The tubulin polymerization assay results suggested that these conjugates inhibit tubulin polymerization with IC50 values 1.12 and 1.59μM respectively. Immunofluorescence analysis also suggested that these conjugates effectively inhibited the microtubule assembly in MCF-7 cells. Further, molecular docking studies indicated that these conjugates 5c and 5p interact and binds efficiently with the tubulin protein. By and large, the results demonstrated that these benzimidazole-oxindole conjugates possess cytotoxic property by inhibiting the tubulin polymerization.

  6. Benzimidazole derivatives as potential dual inhibitors for PARP-1 and DHODH. (United States)

    Abdullah, Iskandar; Chee, Chin Fei; Lee, Yean-Kee; Thunuguntla, Siva Sanjeeva Rao; Satish Reddy, K; Nellore, Kavitha; Antony, Thomas; Verma, Jitender; Mun, Kong Wai; Othman, Shatrah; Subramanya, Hosahalli; Rahman, Noorsaadah Abd


    Poly (ADP-ribose) polymerases (PARPs) play diverse roles in various cellular processes that involve DNA repair and programmed cell death. Amongst these polymerases is PARP-1 which is the key DNA damage-sensing enzyme that acts as an initiator for the DNA repair mechanism. Dihydroorotate dehydrogenase (DHODH) is an enzyme in the pyrimidine biosynthetic pathway which is an important target for anti-hyperproliferative and anti-inflammatory drug design. Since these enzymes share a common role in the DNA replication and repair mechanisms, it may be beneficial to target both PARP-1 and DHODH in attempts to design new anti-cancer agents. Benzimidazole derivatives have shown a wide variety of pharmacological activities including PARP and DHODH inhibition. We hereby report the design, synthesis and bioactivities of a series of benzimidazole derivatives as inhibitors of both the PARP-1 and DHODH enzymes.

  7. Perspectives of Benzimidazole Derivatives as Anticancer Agents in the New Era. (United States)

    Yadav, Snehlata; Narasimhan, Balasubramanian; Kaur, Harmeet


    Cancer is one of the deadliest diseases nowadays and is a great topic for research as the challenging task is to develop new entities with selectivity towards cancerous cells. Heterocyclic compounds are of great importance in medicinal chemistry as they possess an extensive range of therapeutic applications. Benzimidazole is one such important heterocyclic organic compound having structural analogy to nucleotides found in human body and hence is an important pharmacophore in medicinal chemistry. A variety of marketed drugs containing benzimidazole are thiabendazole, flubendazole (anthelmintic), astmizole (antihistaminic), lansoprazole and omeprazole (antiulcerative). In the light of the above facts, this review is an attempt to summarize the collective contributions from the authors around the world in the field of anticancer agents. This review highlights synthetic schemes and anticancer activity results of the research done in the past years.

  8. Aquatris(1H-benzimidazole-κN3(dichloroacetato-κOcopper(II dichloroacetate dihydrate

    Directory of Open Access Journals (Sweden)

    Yu-Feng Li


    Full Text Available The title compound, [Cu(C2HCl2O2(C7H6N23(H2O]C2HCl2O2·2H2O, was prepared by reaction of copper(II 2,2-dichloroacetic acid and benzimidazole in ethanol solution. The compound shows a regular trigonal–bipyramidal stereochemistry. The CuII centre possesses a five-coordinated environment, coordinated by three N atoms from the three benzimidazole ligands and two O atoms, one from the dichloroacetate ligand and the other from the coordinated water molecule. The molecular structure and packing are stabilized by O—H...O and N—H...O hydrogen bonds. The Cl atoms are disordered over two sites, with relative occupancies 0.67 (3 and 0.33 (3.

  9. Synthesis of 2-Substituted Benzimidazoles and 1,5-Disubstituted Benzodiazepines on Alumina and Zirconia Catalysts

    Institute of Scientific and Technical Information of China (English)



    In this study, alumina, zirconia, manganese oxide/alumina, and manganese oxide/zirconia have been investigated for their catalytic activity in the condensation reaction between o-phenylenediamine and an aldehyde or a ketone to synthesise 2-substituted benzimidazoles and 1,5-disubstituted benzodiazepines respectively. Surface area, surface acidity, and morphology of the catalysts have been analysed and correlated with their catalytic activity. The isolated yields of 2-substituted benzimidazoles and 1,5-disubstituted benzodiazepines are in the range of 30% to 95%. A good correlation between the amount of surface acid sites as well as the surface morphology of the catalysts and the catalytic activity has been observed. This method has been found to be simple and economical. The solid supports could be regenerated and reused without much loss in their activity. Further, the solid supports have been also found to be effective as general catalysts in the condensation of o-phenylenediamine with other substituted aldehydes and ketones.

  10. Growth Inhibitory Activity of a Bis-benzimidazole-Bridged Arene Ruthenium Metalla-Rectangle and Prism. (United States)

    Vajpayee, Vaishali; Lee, Sun Mi; Park, Joeng Woo; Dubey, Abhishek; Kim, Hyunuk; Cook, Timothy R; Stang, Peter J; Chi, Ki-Whan


    Two new supramolecular coordination complexes (SCCs), were obtained from the self-assembly of a new bis-benzimidazole bridged Ru acceptor, 4, with dipyridyl and tripyridyl donors, respectively. As part of a growing library of anticancer-active Ru-based SCCs, metalla-prism 6 selectively showed high cytotoxicities relative to cisplatin for a series of cancer cell lines, with IC50 values as low as 8.41 μM for MCF7 cells, as determined from MTS assays.

  11. 4-Methyl-N-(2-phenylethyl-2-propyl-1H-benzimidazole-6-carboxamide

    Directory of Open Access Journals (Sweden)

    Jin-Liang Wang


    Full Text Available There are two independent molecules in the asymmetric unit of the title compound, C20H23N3O, in which the dihedral angles between the phenyl ring of the phenylethylamino group and the benzimidazole system are 73.98 (15 and 15.93 (16°. The crystal packing features N—H...O and N—H...N hydrogen bonds.

  12. New Route to 3-Alkylthiazolo[3,2-a]benzimidazole Derivatives

    Directory of Open Access Journals (Sweden)

    Nicolas Vanthuyne


    Full Text Available 3-Alkyl-thiazolo[3,2-a]benzimidazole derivatives are obtained in high yieldsvia the corresponding 4-alkyl-N-3-(2-aminophenyl-thiazoline-2-thiones which are easilyprepared from 1,2-diaminobenzene, CS2 and halogenoketones. This new route comparesadvantageously with the classical mercaptobenzimidazole routes in term of simplicity,isolated yields and availability of the starting materials.

  13. Synthesis, DNA binding and antitrypanosomal activity of benzimidazole analogues of DAPI. (United States)

    Farahat, Abdelbasset A; Bennett-Vaughn, Cheree; Mineva, Ekaterina M; Kumar, Arvind; Wenzler, Tanja; Brun, Reto; Liu, Yang; Wilson, W David; Boykin, David W


    A series of novel benzimidazole diamidines were prepared from the corresponding dicyano analogues either by applying Pinner methodology (5a-c, 10 and 13a) or by making amidoximes intermediates that were reduced to the corresponding amidines (15a-c). The new amidines were evaluated in vitro against the protozoan parasite Trypanosoma brucei rhodesiense (T. b. r.). The thiophene analogue 5b and the N-methyl compound 15a showed superior antitrypanosomal activity compared to that of the parent I.

  14. Structure-activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH


    Kirubakaran, Sivapriya; Gorla, Suresh Kumar; Sharling, Lisa; Zhang, Minjia; Liu, Xiaoping; Ray, Soumya S.; Iain S. MacPherson; Striepen, Boris; Hedstrom, Lizbeth; Gregory D Cuny


    Cryptosporidium parasites are important waterborne pathogens of both humans and animals. The C. parvum and C. hominis genomes indicate that the only route to guanine nucleotides is via inosine 5'-monophosphate dehydrogenase (IMPDH). Thus the inhibition of the parasite IMPDH presents a potential strategy for treating Cryptosporidium infections. A selective benzimidazole-based inhibitor of C. parvum IMPDH (CpIMPDH) was previously identified in a high throughput screen. Here we report a structur...

  15. Design, synthesis, α-glucosidase inhibitory activity, molecular docking and QSAR studies of benzimidazole derivatives (United States)

    Dinparast, Leila; Valizadeh, Hassan; Bahadori, Mir Babak; Soltani, Somaieh; Asghari, Behvar; Rashidi, Mohammad-Reza


    In this study the green, one-pot, solvent-free and selective synthesis of benzimidazole derivatives is reported. The reactions were catalyzed by ZnO/MgO containing ZnO nanoparticles as a highly effective, non-toxic and environmentally friendly catalyst. The structure of synthesized benzimidazoles was characterized using spectroscopic technics (FT-IR, 1HNMR, 13CNMR). Synthesized compounds were evaluated for their α-glucosidase inhibitory potential. Compounds 3c, 3e, 3l and 4n were potent inhibitors with IC50 values ranging from 60.7 to 168.4 μM. In silico studies were performed to explore the binding modes and interactions between enzyme and synthesized benzimidazoles. Developed linear QSAR model based on density and molecular weight could predict bioactivity of newly synthesized compounds well. Molecular docking studies revealed the availability of some hydrophobic interactions. In addition, the bioactivity of most potent compounds had good correlation with estimated free energy of binding (ΔGbinding) which was calculated according to docked best conformations.

  16. Novel coumarin-benzimidazole derivatives as antioxidants and safer anti-inflammatory agents. (United States)

    Arora, Radha Krishan; Kaur, Navneet; Bansal, Yogita; Bansal, Gulshan


    Inspired from occurrence of anti-inflammatory activity of 3-substituted coumarins and antiulcer activity of various 2-substituted benzimidazoles, novel compounds have been designed by coupling coumarin derivatives at 3-position directly or through amide linkage with benzimidazole nucleus at 2-position. The resultant compounds are expected to exhibit both anti-inflammatory and antioxidant activities along with less gastric toxicity profile. Two series of coumarin-benzimidazole derivatives (4a-e and 5a-e) were synthesized and evaluated for anti-inflammatory activity and antioxidant activity. Compounds 4c, 4d and 5a displayed good anti-inflammatory (45.45%, 46.75% and 42.85% inhibition, respectively, versus 54.54% inhibition by indomethacin) and antioxidant (IC50 of 19.7, 13.9 and 1.2 µmol/L, respectively, versus 23.4 µmol/L for butylatedhydroxytoluene) activities. Evaluation of ulcer index and in vivo biochemical estimations for oxidative stress revealed that compounds 4d and 5a remain safe on gastric mucosa and did not induce oxidative stress in tissues. Calculation of various molecular properties suggests the compounds to be sufficiently bioavailable.

  17. Imidazoles and benzimidazoles as tubulin-modulators for anti-cancer therapy. (United States)

    Torres, Fernando C; García-Rubiño, M Eugenia; Lozano-López, César; Kawano, Daniel F; Eifler-Lima, Vera L; von Poser, Gilsane L; Campos, Joaquín M


    Imidazoles and benzimidazoles are privileged heterocyclic bioactive compounds used with success in the clinical practice of innumerous diseases. Although there are many advancements in cancer therapy, microtubules remain as one of the few macromolecular targets validated for planning active anti-cancer compounds, and the design of drugs that modulate microtubule dynamics in unknown sites of tubulin is one of the goals of the medicinal chemistry. The discussion of the role of new and commercially available imidazole and benzimidazole derivatives as tubulin modulators is scattered throughout scientific literature, and indicates that these compounds have a tubulin modulation mechanism different from that of tubulin modulators clinically available, such as paclitaxel, docetaxel, vincristine and vinblastine. In fact, recent literature indicates that these derivatives inhibit microtubule formation binding to the colchicine site, present good pharmacokinetic properties and are capable of overcoming multidrug resistance in many cell lines. The understanding of the mechanisms involved in the imidazoles/benzimidazoles modulation of microtubule dynamics is very important to develop new strategies to overcome the resistance to anti-cancer drugs and to discover new biomarkers and targets for cancer chemotherapy.

  18. Synthesis and Antiproliferative Activities of Benzimidazole-Based Sulfide and Sulfoxide Derivatives. (United States)

    Gaballah, Samir T; El-Nezhawy, Ahmed O H; Amer, Hassan; Ali, Mamdouh Moawad; Mahmoud, Abeer Essam El-Din; Hofinger-Horvath, Andreas


    The design, synthesis, and in vitro antiproliferative activity of a novel series of sulfide (4a-i) and sulfoxide (5a-h) derivatives of benzimidazole, in which different aromatic and heteroaromatic acetamides are linked to benzimidazole via sulfide (4a-i) and sulfoxide (5a-h) linker, are reported and the structure-activity relationship is discussed. The new derivatives were prepared by coupling 2-(mercaptomethyl)benzimidazole with 2-bromo-N-(substituted) acetamides in dry acetone in the presence of anhydrous potassium carbonate. With very few exceptions, all of the synthesized compounds showed varying antiprolific activities against HepG2, MCF-7, and A549 cell lines. Compound 5a was very similar in potency to doxorubicin as an anticancer drug, with IC50 values 4.1 ± 0.5, 4.1 ± 0.5, and 5.0 ± 0.6 µg/mL versus 4.2 ± 0.5, 4.9 ± 0.6, and 6.1 ± 0.6 µg/mL against HepG2, MCF-7, and A549 cell lines, respectively. In contrast, none of the compounds showed activity against human prostate PC3 cancer cells. Additionally, the sulfoxide derivatives were more potent than the corresponding sulfides.

  19. Critical anthelmintic trials in ponies with four benzimidazoles: mebendazole, cambendazole, fenbendazole, and albendazole. (United States)

    Colglazier, M L; Enzie, F D; Kates, K C


    The comparative efficacy of four benzimidazoles against gastrointestinal parasites of ponies was evaluated by the critical test method. Mebendazole (8.8 mg/kg), cambendazole (20 mg/kg), fenbendazole (5 mg/kg), and albendazole (2.5 and 5 mg/kg) given in single oral doses were highly effective against adult large strongylids (Strongylus vulgaris, S. endentatus, S. equinus) and adult small strongylids (genera identified in order of frequency: Cylicostephanus, Cylicocyclus, Cyathostomum, Triodontophorus, Poteriostomum, Oesophagodontus, Cylicodontophorus, Gyalocephalus, and Craterostomum). Limited data indicated that all benzimidazoles were completely effective against adult Oxyuris equi and 95 to 100% effective against the 4th stage larvae. There was activity also against the large roundworm, Parascaris equorum, although the low levels of infection and skew distribution among the test animals did not permit a definitive determination of efficacy. Habronema muscae, Draschia megastoma, and Trichostrongylus axei were found in digests of the stomach but none were recovered in the feces after treatment; percent efficacy for these species was not calculated. None of the benzimidazoles showed activity against stomach bots, Gasterophilus spp., and tapeworms, Anoplocephala spp. nor against immature large and small strongylids outside the lumen of the digestive tract.

  20. A trisubstituted benzimidazole cell division inhibitor with efficacy against Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Susan E Knudson

    Full Text Available Trisubstituted benzimidazoles have demonstrated potency against Gram-positive and Gram-negative bacterial pathogens. Previously, a library of novel trisubstituted benzimidazoles was constructed for high throughput screening, and compounds were identified that exhibited potency against M. tuberculosis H37Rv and clinical isolates, and were not toxic to Vero cells. A new series of 2-cyclohexyl-5-acylamino-6-N, N-dimethylaminobenzimidazoles derivatives has been developed based on SAR studies. Screening identified compounds with potency against M. tuberculosis. A lead compound from this series, SB-P17G-A20, was discovered to have an MIC of 0.16 µg/mL and demonstrated efficacy in the TB murine acute model of infection based on the reduction of bacterial load in the lungs and spleen by 1.73 ± 0.24 Log10 CFU and 2.68 ± Log10 CFU, respectively, when delivered at 50 mg/kg by intraperitoneal injection (IP twice daily (bid. The activity of SB-P17G-A20 was determined to be concentration dependent and to have excellent stability in mouse and human plasma, and liver microsomes. Together, these studies demonstrate that SB-P17G-A20 has potency against M. tuberculosis clinical strains with varying susceptibility and efficacy in animal models of infection, and that trisubstituted benzimidazoles continue to be a platform for the development of novel inhibitors with efficacy.

  1. Synthesis, antimicrobial and cytotoxic activity of novel azetidine-2-one derivatives of 1H-benzimidazole

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    Malleshappa Noolvi


    Full Text Available A series of 1-methyl-N-[(substituted-phenylmethylidene-1H-benzimidazol-2-amines (4a–4g were prepared via the formation of 1-methyl-1H-benzimidazol-2-amine (3, which was prepared by the cycloaddition of o-phenylenediamine (1 with cyanogen bromide in the presence of aqueous base followed by N-methylation with methyl iodide in the presence of anhydrous potassium carbonate in dry acetonitrile. Moreover, the four-membered β-lactam ring was introduced by the cycloaddition of 4a–4g and chloroacetyl chloride in the presence of triethylamine catalyst to give 3-chloro-1-(1-methyl-1H-benzimidazol-2-yl-(4′-substituted-phenylazetidin-2-one 5a–5g. A total of 14 compounds were synthesized and characterized by IR, 1H NMR, 13C NMR and Mass spectral technique, in addition they were evaluated for anti-bacterial and cytotoxic properties. Among the chemicals tested 4a, 4b, 5a, 5b, 5g exhibited good antibacterial activity and 5f, 5g shown good cytotoxic activity in vitro.

  2. Electrochemistry of interaction of 2-(2-nitrophenyl)-benzimidazole derivatives with DNA. (United States)

    Catalán, Mabel; Alvarez-Lueje, Alejandro; Bollo, Soledad


    In this study the interaction between new benzimidazole molecules, 2-(2-nitrophenyl)-1H-benzimidazole (NB) and N-benzoyl-2-(2-nitrophenyl)-benzimidazole (BNB), with dsDNA and ssDNA was assessed at pH 7.4. Using differential pulse voltammetry at glassy carbon electrode, both molecules were electrochemically reduced due to the presence of a nitro group in their structures. When DNA was added to the solution, the electrochemical signal of NB and BNB decreased and shifted to more negative potentials. The interaction mode was electrostatic when ionic strength was low. Under this condition DNA-nitro complexes were characterized and binding constant values of 8.22 x 10(4)M(-1) and 3.08 x 10(6)M(-1) for NB and BNB with dsDNA were determined. On the other hand, only NB was able to interact when a high concentration of NaCl was used. Finally, a glassy carbon electrode modified with carbon nanotubes and DNA was tested in order to determine the nitrocompound in solution. The electrochemical reduction of the nitrocompound adsorbed on GCE/CHIT-CNT/DNA was used as an analytical signal. Using 10 min as accumulation time, a linear dependence was observed between 20 and 80 microM nitrocompound concentrations and the electrode response. Detection and quantification limits in the range of microM were determined.

  3. Novel organic dyes based on phenyl-substituted benzimidazole for dye sensitized solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Saltan, Gözde Murat [Department of Chemistry, Faculty of Arts and Science, Celal Bayar University, Yunus Emre, 45140 Manisa (Turkey); Dinçalp, Haluk, E-mail: [Department of Chemistry, Faculty of Arts and Science, Celal Bayar University, Yunus Emre, 45140 Manisa (Turkey); Kıran, Merve; Zafer, Ceylan [Solar Energy Institute, Ege University, Bornova, 35100 Izmir (Turkey); Erbaş, Seçil Çelik [Celal Bayar University, Materials Engineering Department, Faculty of Engineering, Yunus Emre, 45140 Manisa (Turkey)


    Two new sensitizers derived from benzimidazole core for dye-sensitized solar cell (DSSC) applications were designed and synthesized as D–π–A structures, in which two phenyl-substituted benzimidazole group, a phenyl ring and a cyanoacrylic acid were used as the electron donor, π-conjugated linkage and the electron acceptor, respectively. Effect of methoxy- and N,N-dimetylamino- moieties attached to the phenyl groups of benzimidazole were investigated by means of optical and photovoltaic measurements. The compounds exhibit broad absorption maximum at 387 nm with the tail extending up to 500 nm on TiO{sub 2}-coated thin film. The longer wavelength absorption band around 360 nm and the much longer decay components could be attributed to the existence of charge transfer state of the dyes in solutions. DSSC device fabricated by using methoxy substituted dye (BI5a) as a sensitizer shows much better incident photon-to-current conversion efficiency (IPCE) of 64% giving cell efficiency of 2.68%. - Graphical abstract: Display Omitted - Highlights: • Long decay times suggest the delayed fluorescence caused by the existence of ICT. • The best solar energy conversion efficiency was obtained for BI5a dye (2.68%). • More fluorescent BI5a dye gives higher photocurrent generation.

  4. 2-(4-Hydroxyphenyl-1H-benzimidazol-3-ium chloride monohydrate

    Directory of Open Access Journals (Sweden)

    Jazmin E. González-Padilla


    Full Text Available The title molecular salt, C13H11N2O+·Cl−·H2O, crystallizes as a monohydrate. In the cation, the phenol and benzimidazole rings are almost coplanar, making a dihedral angle of 3.18 (4°. The chloride anion and benzimidazole cation are linked by two N+—H...Cl− hydrogen bonds, forming chains propagating along [010]. These chains are linked through O—H...Cl hydrogen bonds involving the water molecule and the chloride anion, which form a diamond core, giving rise to the formation of two-dimensional networks lying parallel to (10-2. Two π–π interactions involving the imidazolium ring with the benzene and phenol rings [centroid–centroid distances = 3.859 (3 and 3.602 (3 Å, respectively], contribute to this second dimension. A strong O—H...O hydrogen bond involving the water molecule and the phenol substituent on the benzimidazole unit links the networks, forming a three-dimensional structure.

  5. Thermostability and photophysical properties of mixed-ligand carboxylate/benzimidazole Zn(II)-coordination polymers

    Energy Technology Data Exchange (ETDEWEB)

    Barros, Bráulio Silva, E-mail: [School of Science and Technology, Federal University of Rio Grande do Norte (UFRN), Campus Universitário Lagoa Nova, 59078-970 Natal, RN (Brazil); Chojnacki, Jaroslaw [Department of Inorganic Chemistry, Chemical Faculty, Gdansk University of Technology, G. Narutowicza 11/12, 80-233 Gdansk (Poland); Macêdo Soares, Antonia Alice; Kulesza, Joanna; Lourenço da Luz, Leonis; Júnior, Severino Alves [Department of Fundamental Chemistry, Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego, 1235 – Cidade Universitária, 50670-901 Recife, PE (Brazil)


    The reaction between Zn(NO{sub 3}){sub 2}·6H{sub 2}O or Zn(CH{sub 3}COO){sub 2}·2H{sub 2}O and isophthalic acid (1,3-H{sub 2}bdc) in the presence of benzimidazole (Hbzim) in dimethylformamide (DMF)/ethanol (EtOH)/H{sub 2}O solvent mixture at room temperature yielded two structurally different coordination polymers: [Zn{sub 2}(1,3-bdc){sub 2}(Hbzim){sub 2}] (1) and [Zn{sub 2}(1,3-bdc)(bzim){sub 2}] (2). (1) is a 2D-layered framework with a molecule of benzimidazole coordinated to the Zn center, whereas (2) is a 3D framework with benzimidazolate species acting as a co-ligand and bridging two Zn(II) ions. Reactions performed at 90 °C led to the formation of coordination polymers structurally similar to (2), independently of the Zn(II) source used. In the absence of benzimidazole, the reaction between ZnAc{sub 2}.2H{sub 2}O and 1,3-H{sub 2}bdc at 90 °C resulted in the formation of (3), a 3D coordination polymer Zn(HCOO){sub 3}(Me{sub 2}NH{sub 2}{sup +}). It was observed that the thermostability and the photophysical properties of (1) and (2) are strongly dependent on the coordination modes and packing of benzimidazole in the solid state. These materials present photoluminescence in the wide range of the spectrum, from UV to IR. A full understanding of a physical process occurring in these intriguing systems, including complete energy level diagrams with possible transitions were provided. - Graphical abstract: Display Omitted - Highlights: • Structurally different Zn(II)-coordination polymers were prepared. • The formation of frameworks was counter anion and temperature dependent. • Photoluminescence in the wide range of the spectrum, from UV to IR was observed. • Thermostability and luminescence depended on bzim packing in the structure.

  6. Conjugation of benzylvanillin and benzimidazole structure improves DNA binding with enhanced antileukemic properties. (United States)

    Al-Mudaris, Zena A; Majid, Aman S A; Ji, Dan; Al-Mudarris, Ban A; Chen, Shih-Hsun; Liang, Po-Huang; Osman, Hasnah; Jamal Din, Shah Kamal Khan; Abdul Majid, Amin M S


    Benzyl-o-vanillin and benzimidazole nucleus serve as important pharmacophore in drug discovery. The benzyl vanillin (2-(benzyloxy)-3-methoxybenzaldehyde) compound shows anti-proliferative activity in HL60 leukemia cancer cells and can effect cell cycle progression at G2/M phase. Its apoptosis activity was due to disruption of mitochondrial functioning. In this study, we have studied a series of compounds consisting of benzyl vanillin and benzimidazole structures. We hypothesize that by fusing these two structures we can produce compounds that have better anticancer activity with improved specificity particularly towards the leukemia cell line. Here we explored the anticancer activity of three compounds namely 2-(2-benzyloxy-3-methoxyphenyl)-1H-benzimidazole, 2MP, N-1-(2-benzyloxy-3-methoxybenzyl)-2-(2-benzyloxy-3-methoxyphenyl)-1H-benzimidazole, 2XP, and (R) and (S)-1-(2-benzyloxy-3-methoxyphenyl)-2, 2, 2-trichloroethyl benzenesulfonate, 3BS and compared their activity to 2-benzyloxy-3-methoxybenzaldehyde, (Bn1), the parent compound. 2XP and 3BS induces cell death of U937 leukemic cell line through DNA fragmentation that lead to the intrinsic caspase 9 activation. DNA binding study primarily by the equilibrium binding titration assay followed by the Viscosity study reveal the DNA binding through groove region with intrinsic binding constant 7.39 µM/bp and 6.86 µM/bp for 3BS and 2XP respectively. 2XP and 3BS showed strong DNA binding activity by the UV titration method with the computational drug modeling showed that both 2XP and 3BS failed to form any electrostatic linkages except via hydrophobic interaction through the minor groove region of the nucleic acid. The benzylvanillin alone (Bn1) has weak anticancer activity even after it was combined with the benzimidazole (2MP), but after addition of another benzylvanillin structure (2XP), stronger activity was observed. Also, the combination of benzylvanillin with benzenesulfonate (3BS) significantly improved the

  7. Conjugation of benzylvanillin and benzimidazole structure improves DNA binding with enhanced antileukemic properties.

    Directory of Open Access Journals (Sweden)

    Zena A Al-Mudaris

    Full Text Available Benzyl-o-vanillin and benzimidazole nucleus serve as important pharmacophore in drug discovery. The benzyl vanillin (2-(benzyloxy-3-methoxybenzaldehyde compound shows anti-proliferative activity in HL60 leukemia cancer cells and can effect cell cycle progression at G2/M phase. Its apoptosis activity was due to disruption of mitochondrial functioning. In this study, we have studied a series of compounds consisting of benzyl vanillin and benzimidazole structures. We hypothesize that by fusing these two structures we can produce compounds that have better anticancer activity with improved specificity particularly towards the leukemia cell line. Here we explored the anticancer activity of three compounds namely 2-(2-benzyloxy-3-methoxyphenyl-1H-benzimidazole, 2MP, N-1-(2-benzyloxy-3-methoxybenzyl-2-(2-benzyloxy-3-methoxyphenyl-1H-benzimidazole, 2XP, and (R and (S-1-(2-benzyloxy-3-methoxyphenyl-2, 2, 2-trichloroethyl benzenesulfonate, 3BS and compared their activity to 2-benzyloxy-3-methoxybenzaldehyde, (Bn1, the parent compound. 2XP and 3BS induces cell death of U937 leukemic cell line through DNA fragmentation that lead to the intrinsic caspase 9 activation. DNA binding study primarily by the equilibrium binding titration assay followed by the Viscosity study reveal the DNA binding through groove region with intrinsic binding constant 7.39 µM/bp and 6.86 µM/bp for 3BS and 2XP respectively. 2XP and 3BS showed strong DNA binding activity by the UV titration method with the computational drug modeling showed that both 2XP and 3BS failed to form any electrostatic linkages except via hydrophobic interaction through the minor groove region of the nucleic acid. The benzylvanillin alone (Bn1 has weak anticancer activity even after it was combined with the benzimidazole (2MP, but after addition of another benzylvanillin structure (2XP, stronger activity was observed. Also, the combination of benzylvanillin with benzenesulfonate (3BS significantly improved

  8. Synthesis and Characterization of 2-[1h- Benzimidazole- 2yl-Sulfanyl]-N-[(E-Furan-2-Yl- Methylidene] Aceto Hydrazide

    Directory of Open Access Journals (Sweden)

    Ramesh Dhani


    Full Text Available Heterocyclic chemistry comprises at least half of all organic chemistry research worldwide. In particular, heterocyclic structures form the basis of many pharmaceutical, agrochemical and veterinary products. The benzimidazole contains a phenyl ring fused to an imidazole ring, as indicated in the structure of benzimidazole. Diversity of biological response profile has attracted considerable interest of several researchers across the globe to explore this skeleton for its assorted therapeutic significance. By using different synthetic methods new benzimidazole derivatives were synthesized and further Melting points were determined by using Precision melting point apparatus in open capillaries and are uncorrected. The purity of the compounds was checked by TLC on silica gel G plates using n-Hexane, ethyl acetate (1:3 and methanol: chloroform (1:9 solvent system. The synthesized benzimidazole derivatives were characterized by IR, 1H NMR spectral analysis. Benzimidazole is a lead nucleus for future developments to get effective compounds.

  9. 1-{[Dimethyl(phenylsilyl]methyl}-3-(2-phenylethyl-1H-benzimidazol-3-ium bromide monohydrate

    Directory of Open Access Journals (Sweden)

    Mehmet Akkurt


    Full Text Available The title compound, C24H27N2Si+·Br−·H2O, was synthesized from 1-(dimethylphenylsilylmethyl-1H-benzimidazole and (2-bromoethylbenzene in dimethylformamide. The benzimidazole ring system is nearly planar, with a maximum deviation of 0.015 (5 Å, and forms dihedral angles of 73.0 (3 and 39.6 (2°, with the phenyl rings. In the crystal, molecules are linked by O—H...Br, C—H...Br and C—H...O hydrogen bonds. In addition, the structure features π–π stacking interactions, with a face-to-face separation of 3.644 (3 Å between parallel benzimidazole ring systems.

  10. 2-Anilino-4-(benzimidazol-2-yl)pyrimidines--a multikinase inhibitor scaffold with antiproliferative activity toward cancer cell lines. (United States)

    Determann, Renate; Dreher, Jan; Baumann, Knut; Preu, Lutz; Jones, Peter G; Totzke, Frank; Schächtele, Christoph; Kubbutat, Michael H G; Kunick, Conrad


    2-Anilino-4-(benzimidazol-2-yl)-pyrimidines, synthesized by reaction of a readily available benzimidazole-substituted enaminone with suitable arylguanidines, were shown to inhibit four cancer-related protein kinases (Aurora B, PLK1, FAK, and VEGF-R2). The most potent derivative exhibited antiproliferative activity for several cancer cell lines of the NCI in vitro cell line panel in submicromolar concentrations. Both the anilinopyrimidine structure and the substitution pattern at the aniline ring appear to be important for the protein kinase inhibitory activity.

  11. Synthesis and Cytotoxic Evaluation of Pyrrole Hetarylazoles Containing Benzimidazole/Pyrazolone/1,3,4-Oxadiazole Motifs. (United States)

    Mochona, Bereket; Jackson, Timothy; McCauley, DeCoria; Mazzio, Elizabeth; Redda, Kinfe K


    Azomethine linked pyrrole bishetarylazoles containing benzimidazole/pyrazolone/1,3,4-oxadiazole were synthesized in satisfactory yields. Their structures were confirmed by IR, (1)H-NMR, (13)C-NMR and elemental analysis. Evaluation for the cytotoxic activities In vitro against a panel of breast cancer cell lines (MDA-AB-231, BT-474 and Ishikawa cells) revealed that the pyrrole-benzimidazole hybrids are more potent than the pyrazolone and 1,3,4-oxadiazole hybrids in all cell lines. Compound (9) displayed promising cytotoxicity against BT-474 cell line with IC50 values, 7.7 µM.

  12. 2-[4-(1H-1,2,4-Triazol-1-ylphenyl]-1H-benzimidazole

    Directory of Open Access Journals (Sweden)

    Long-Huai Cheng


    Full Text Available In the title compound, C15H11N5, the benzimidazole ring system is nearly planar [maximum deviation = 0.039 (2 Å], and is oriented at a dihedral angle of 28.85 (10° with respect to the benzene ring; the dihedral angle between the triazole and benzene rings is 17.30 (15°. In the crystal N—H...N hydrogen bonds link the molecules into chains. Weak C—H...N interactions are also present.

  13. Cytotoxicity and DNA interactions of some platinum(II) complexes with substituted benzimidazole ligands. (United States)

    Ozçelik, Azime Berna; Utku, Semra; Gümüş, Fatma; Keskin, Ayten Çelebi; Açık, Leyla; Yılmaz, Sükran; Ozgüngör, Adeviye


    In the present study, four Pt(II) complexes with 2-ethyl (1)/or benzyl (2)/or p-chlorobenzyl (3)/or 2-phenoxymethyl (4) benzimidazole carrier ligands were evaluated for their in vitro cytotoxic activities against the human HeLa cervix, oestrogen receptor-positive MCF-7 breast, and oestrogen receptor-negative MDA-MB 231 breast cancer cell lines. The plasmid DNA interactions and inhibition of the BamHI restriction enzyme activities of the complexes were also studied. Complex 3 was found to be more active than carboplatin for all examined cell lines and comparable with cisplatin, except for the HeLa cell line.

  14. Synthesis of new conjugated coumarin-benzimidazole hybrids and their anticancer activity. (United States)

    Paul, Kamaldeep; Bindal, Shweta; Luxami, Vijay


    A series of novel coumarin-benzimidazole hybrids, 3-(1H-benzo[d]imidazol-2-yl)-7-(substituted amino)-2H-chromen-2-one derivatives of biological interest were synthesized. Six out of the newly synthesized compounds were screened for in vitro antitumor activity against preliminary 60 tumor cell lines panel assay. A significant inhibition for cancer cells was observed with compound 8 (more than 50% inhibition) compared with other compounds and active known drug 5-fluorouracil (in some cell lines) as positive control. Compound 8 displayed appreciable anticancer activities against leukemia, colon cancer and breast cancer cell lines.

  15. Synthesis and evaluation of benzimidazole carbamates bearing indole moieties for antiproliferative and antitubulin activities. (United States)

    Guan, Qi; Han, Chunming; Zuo, Daiying; Zhai, Min'an; Li, Zengqiang; Zhang, Qian; Zhai, Yanpeng; Jiang, Xuewei; Bao, Kai; Wu, Yingliang; Zhang, Weige


    A series of novel benzimidazole carbamates bearing indole moieties with sulphur or selenium atoms connecting the aromatic rings were synthesised and evaluated for their antiproliferative activities against three human cancer cell lines (SGC-7901, A-549 and HT-1080) using an MTT assay. Compounds 10a, 10b, 7a, 7b and 7f showed significant activities against these cell lines. The most potent compound in this series, 10a, was selected to investigate its antitumour mechanism. In addition, molecular docking studies suggested that compound 10a interacts very closely with the nocodazole docking pose through hydrogen bonds at the colchicine binding site of tubulin.

  16. Synthesis, in vitro antimicrobial and cytotoxic activities of novel pyrimidine-benzimidazol combinations. (United States)

    Chen, Peng-Ju; Yang, Ang; Gu, Yi-Fei; Zhang, Xiao-Song; Shao, Kun-Peng; Xue, Deng-Qi; He, Peng; Jiang, Teng-Fei; Zhang, Qiu-Rong; Liu, Hong-Min


    A series of novel 4-substituted-2-{[(1H-benzo[d]imidazol-2-yl)methyl] thio}-6-methylpyrimidine derivatives were designed, synthesized and evaluated for their cytotoxic activities against four human cancer cell lines and inhibitory activities against five type culture strains in vitro. Some of synthetic pyrimidine-benzimidazol combinations showed good inhibitory activities against Stenotrophomonas maltophilia, especially compounds 7b and 7c. Compounds 7a and 7d exhibited enhanced activities against MGC-803 in vitro, when compared to 5-Fu.

  17. Design and synthesis of new biprivileged molecular scaffolds: indolo-fused benzodiazepinyl/quinoxalinyl benzimidazoles. (United States)

    Barve, Indrajeet J; Chen, Chan-Yu; Salunke, Deepak B; Chung, Wen-Sheng; Sun, Chung-Ming


    The present article describes the design and synthesis of new biprivileged molecular scaffolds with diverse structural features. Commercially available, simple heterocyclic building blocks such as 4-fluoro-3-nitrobenzoic acid, 2-chloro-3-nitrobenzoic acid, and indoline were utilized for the synthesis of the novel heterocycles. Pictet-Spengler-type condensation was used as a key step to construct tetracyclic indolo-benzodiazepines and indolo-quinoxalines linked with substituted benzimidazoles. Analysis of single crystals of representative compounds showed that these molecular skeletons have the potential to present various substituents with distinct three-dimensional orientations.

  18. 1-(4-Methylbenzyl-1H-benzimidazol-2(3H-one

    Directory of Open Access Journals (Sweden)

    Lahcen El Ammari


    Full Text Available In the title compound, C15H14N2O, the fused five- and six-membered ring system is essentially planar, the maximum deviation from the mean plane being 0.009 (1 Å. The benzimidazol-2(3H-one residue is nearly perpendicular to the benzyl ring, forming a dihedral angle of 77.41 (6°. In the crystal, inversion dimers are formed by pairs of N—H...O hydrogen bonds; these dimers are linked by weak C—H...O interactions into a two-dimensional array in the (102 plane.

  19. Design, synthesis and in vitro antiprotozoal activity of benzimidazole-pentamidine hybrids. (United States)

    Torres-Gómez, Héctor; Hernández-Núñez, Emanuel; León-Rivera, Ismael; Guerrero-Alvarez, Jorge; Cedillo-Rivera, Roberto; Moo-Puc, Rosa; Argotte-Ramos, Rocío; Rodríguez-Gutiérrez, María Del Carmen; Chan-Bacab, Manuel Jesús; Navarrete-Vázquez, Gabriel


    A series of ten novel hybrids from benzimidazole and pentamidine were prepared using a short synthetic route. Each compound was tested in vitro against the protozoa Trichomonas vaginalis, Giardia lamblia, Entamoeba histolytica, Leishmania mexicana, and Plasmodium berghei, in comparison with pentamidine and metronidazole. Some analogues showed high bioactivity in the low micromolar range (IC(50)pentamidine, respectively. This compound was 23-, 108-, and 13-fold more active than pentamidine against T. vaginalis, E. histolytica and L. mexicana, respectively. Studying further structure-activity relationships through the use of bioisosteric substitution in these hybrids should provide new leads against protozoal diseases.

  20. 2-Heteroaryl Benzimidazole Derivatives as Melanin Concentrating Hormone Receptor 1 (MCH-R1) Antagonists

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Chae Jo; Kim, Jeong Young; Lee, Byung Ho; Oh, Kwangseok; Yi, Kyu Yang [Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of)


    A novel series of 2-heteroaryl substituted benzimidazole derivatives, containing the piperidinylphenyl acetamide group at the 1-position, were synthesized and evaluated as MCH-R1 antagonists. Extensive SAR investigation probing the effects of C-2 heteroaryl group led to the identification of 2-[2-(pyridin-3-yl)ethyl] analog 3o, which exhibits highly potent MCH-R1 binding activity with an IC{sub 50} value of 1 nM. This substance 3o also has low hERG binding activity, good metabolic stability, and favorable pharmacokinetic properties.

  1. Glycerol Containing Triacetylborate Mediated Syntheses of Novel 2-Heterostyryl Benzimidazole Derivatives: A Green Approach

    Directory of Open Access Journals (Sweden)

    Ashok Kumar Taduri


    Full Text Available A very simple, mild, efficient, and novel green methodology has been developed for the syntheses of some 2-hetero/styryl-benzimidazoles. Title compounds were synthesized by the condensation of o-phenylenediamine with cinnamic acids at 150–180°C for 5-6 h using glycerol containing triacetylborate (10–20 mol% as the reaction medium. In an alternative approach, condensation of 2-methylbenzimidazole derivatives with aromatic aldehydes was done using glycerol containing triacetylborate (10–20 mol% as the reaction medium.

  2. Sulfonated copolyimide membranes derived from a novel diamine monomer with pendant benzimidazole groups for fuel cells

    DEFF Research Database (Denmark)

    Li, Wei; Guo, Xiaoxia; Aili, David;


    . A series of sulfonated copolyimides (SPI) are prepared via random copolymerizatio of 1,4,5,8-naphthalenetetracarboxylic dianhydride (NTDA) with a new diamine monomer with pendant benzimidazole groups, 2,2'-bis(4-(1H-benzo[d]imidazol-2-yl)phenoxy)benzidine (BIPOB), and a sulfonated diamine monomer 4,4'-bis...... pendant groups significantly improves the hydrolytic stability as well as the radical oxidative stability of the membranes. In addition, the SPI membranes exhibit high proton conductivities of 0.1 S cm(-1) in the fully hydrated state at 60 degrees C and high elastic modulus and tensile strength...

  3. (S-2-(2-Pyrrolidinio-1H-benzimidazol-3-ium dichloride monohydrate

    Directory of Open Access Journals (Sweden)

    Dai Jing


    Full Text Available In the title compound, C11H15N32+·2Cl−·H2O, one N atom of the imidazole ring and the N atom of the pyrrolidine ring are protonated. The crystal structure is stabilized by aromatic π–π interactions between the benzene rings of neighbouring benzimidazole systems [centroid–centroid duistance = 3.712 (2 Å]. The crystal structure is further stabilized by intermolecular N—H...Cl, O—H...Cl and N—H...O hydrogen bonds.

  4. Efficient Synthesis of Functionalized Benzimidazoles and Perimidines: Ytterbium Chloride Catalyzed CmC Bond Cleavage%Efficient Synthesis of Functionalized Benzimidazoles and Perimidines: Ytterbium Chloride Catalyzed CmC Bond Cleavage

    Institute of Scientific and Technical Information of China (English)

    Cai, Lijian; Ji, Xiaofeng; Yao, Zhigang; Xu, Fan; Shen, Qi


    An efficient method is developed for the synthesis of functionalized benzimidazoles and perimidines by the condensation of aryl diamines with β-carbonyl compounds catalyzed by ytterbium chloride. The reactions give good yields under mild conditions. A mechanism involving a lanthanide activated C--C bond cleavage is proposed.

  5. Design, synthesis, molecular docking and biological evaluation of new dithiocarbamates substituted benzimidazole and chalcones as possible chemotherapeutic agents. (United States)

    Bacharaju, Keerthana; Jambula, Swathi Reddy; Sivan, Sreekanth; Jyostnatangeda, Saritha; Manga, Vijjulatha


    A series of novel dithiocarbamates with benzimidazole and chalcone scaffold have been designed synthesised and evaluated for their antimitotic activity. Compounds 4c and 9d display the most promising antimitotic activity with IC(50) of 1.66 μM and 1.52 μM respectively.

  6. On the antitumor properties of novel cyclometalated benzimidazole Ru(II), Ir(III) and Rh(III) complexes. (United States)

    Yellol, Gorakh S; Donaire, Antonio; Yellol, Jyoti G; Vasylyeva, Vera; Janiak, Christoph; Ruiz, José


    Smart design and efficient synthesis of benzimidazole Ru, Ir and Rh cyclometalated complexes are reported with promising cytotoxic activity against HT29, T47D, A2780 and A2780cisR cancer cell lines. Their apoptosis, accumulation, cell cycle arrest, protein binding and DNA binding effects are also discussed.

  7. First cascade Mitsunobu reactions for the synthesis of 2-benzoxazole-N-phenyl and 2-benzimidazole-N-phenyl derivatives. (United States)

    Yan, Yu; Zhong, Qifei; Zhao, Nan; Liu, Gang


    An efficient method has been developed via cascade Mitsunobu reactions to synthesize 2-benzoxazole-N-phenyl and 2-benzimidazole-N-phenyl derivatives, which are common structural motifs in medicinal chemistry. This method also provides a new application of the Mitsunobu reaction.

  8. The antimitotic properties of the benzimidazole fungicide carbendazim and a mechanism of resistance to this compound in Aspergillus nidulans

    NARCIS (Netherlands)

    Davidse, L.C.


    Systemic benzimidazole fungicides are well-known for their pronounced ability to control a large number of fungal plant diseases. On the other hand development of resistance in fungi to these compounds is as well widely known.Biochemical aspects of both fungitoxic action and resistance in fungi are

  9. Synthesis and structural studies of amino amide salts derived from 2-(aminomethyl)benzimidazole and α-amino acids (United States)

    Avila-Montiel, Concepción; Tapia-Benavides, Antonio R.; Falcón-León, Martha; Ariza-Castolo, Armando; Tlahuext, Hugo; Tlahuextl, Margarita


    2-{[(Ammoniumacetyl)amino]methyl}-1H-benzimidazol-3-ium dichloride 4, 2-{[(2-ammoniumpropanoyl)amino]methyl}-1H-benzimidazol-3-ium dichloride 5, and 2-{[(2-ammonium-3-phenylpropanoyl)amino]methyl}-1H-benzimidazol-3-ium dichloride 6 amino amides were synthesized via condensation of 2AMBZ dihydrochloride with the corresponding amino acid. Compounds 7-12 were obtained by replacing chloride ions (in salts 4-6) with nitrate or tetrachlorozincate ions. The results of X-ray diffraction crystallographic studies indicated that the geometries, charges and sizes of the anions are essential for the formation of the strong hydrogen bond interactions of compounds 4, 5, 9-12. Moreover, in most cases, the presence of water and solvent molecules stabilizes the supramolecular structures of these compounds. Nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy indicated that the presence of chloride or tetrachlorozincate anions increases the acidity of the benzimidazolic and amide groups more significantly than the presence of nitrate anions. However, Quantum Theory of Atoms in Molecules (QTAIM) computations of the crystal structures demonstrate that amino amides interact more strongly with NO3- than with Cl- and ZnCl42- anions; this difference explains the spectroscopic results.

  10. Antiproliferative effect of benzimidazole anthelmintics albendazole, ricobendazole, and flubendazole in intestinal cancer cell lines. (United States)

    Králová, Věra; Hanušová, Veronika; Staňková, Petra; Knoppová, Kateřina; Čáňová, Kristýna; Skálová, Lenka


    This study aimed to test the antiproliferative effect of three benzimidazole anthelmintics in intestinal cancer cells and to investigate whether these drugs, which inhibit tubulin polymerization, can potentiate the efficacy of the microtubule-stabilizing drug paclitaxel (PTX). Four intestinal cancer cell lines, SW480, SW620, HCT8, and Caco2, with different origins and growth characteristics were used. The antiproliferative effect of albendazole (ABZ), ricobendazole (RBZ), flubendazole (FLU), and their combinations with PTX was tested using three different end-point viability assays, cell cycle distribution analysis, and the x-CELLigence System for real-time cell analysis. ABZ and FLU inhibited cell proliferation significantly in a concentration-dependent and time-dependent manner through cell arrest in the G2/M phase. RBZ was not effective at any concentration tested. The cell lines differed in sensitivity to FLU and ABZ, with HCT8 being the most sensitive, showing IC₅₀ values for ABZ and FLU that reached 0.3 and 0.9 μmol/l, respectively. Combinations of PTX+ABZ and PTX+FLU decreased cell viability more effectively when compared with treatment with individual drugs alone. The anthelmintic benzimidazole drugs ABZ and FLU show a significant cytostatic effect and potentiate the efficacy of PTX in intestinal cancer cells.

  11. Antiproliferative activity of bicyclic benzimidazole nucleosides: synthesis, DNA-binding and cell cycle analysis. (United States)

    Sontakke, Vyankat A; Lawande, Pravin P; Kate, Anup N; Khan, Ayesha; Joshi, Rakesh; Kumbhar, Anupa A; Shinde, Vaishali S


    An efficient route was developed for synthesis of bicyclic benzimidazole nucleosides from readily available d-glucose. The key reactions were Vörbruggen glycosylation and ring closing metathesis (RCM). Primarily, to understand the mode of DNA binding, we performed a molecular docking study and the binding was found to be in the minor groove region. Based on the proposed binding model, UV-visible and fluorescence spectroscopic techniques using calf thymus DNA (CT-DNA) demonstrated a non-intercalative mode of binding. Antiproliferative activity of nucleosides was tested against MCF-7 and MDA-MB-231 breast cancer cell lines and found to be active at low micromolar concentrations. Compounds and displayed significant antiproliferative activity as compared to and with the reference anticancer drug, doxorubicin. Cell cycle analysis showed that nucleoside induced cell cycle arrest at the S-phase. Confocal microscopy has been performed to validate the induction of cellular apoptosis. Based on these findings, such modified bicyclic benzimidazole nucleosides will make a significant contribution to the development of anticancer drugs.

  12. Synthesis and activity of benzimidazole-1,3-dioxide inhibitors of separase. (United States)

    Do, Ha T; Zhang, Nenggang; Pati, Debananda; Gilbertson, Scott R


    Due to the oncogenic activity of cohesin protease, separase in human cancer cells, modulation of separase enzymatic activity could constitute a new therapeutic strategy for targeting resistant, separase-overexpressing aneuploid tumors. Herein, we report the synthesis, structural information, and structure-activity relationship (SAR) of separase inhibitors based on modification of the lead molecule 2,2-dimethyl-5-nitro-2H-benzimidazole-1,3-dioxide, named Sepin-1, (1) identified from a high-throughput-screen. Replacement of -NO2 at C5 with other functional groups reduce the inhibitory activity in separase enzymatic assay. Substitution of the two methyl groups with other alkyl chains at the C2 moderately improves the effects on the inhibitory activity of those compounds. Modifications on 2H-benzimidazole-1,3-dioxide or the skeleton have variable effect on inhibition of separase enzymatic activity. Density-functional theory (DFT) calculations suggest there may be a correlation between the charges on the oxide moieties on these compounds and their activity in inhibiting separase enzyme.

  13. Hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives and evaluation of their anticancer and antimycobacterial activity. (United States)

    Mantu, Dorina; Antoci, Vasilichia; Moldoveanu, Costel; Zbancioc, Gheorghita; Mangalagiu, Ionel I


    The design, synthesis, structure, and in vitro anticancer and antimycobacterial activity of new hybrid imidazole (benzimidazole)/pyridine (quinoline) derivatives are described. The strategy adopted for synthesis is straight and efficient, involving a three-step setup procedure: N-acylation, N-alkylation, and quaternization of nitrogen heterocycle. The solubility in microbiological medium and anticancer and antimycobacterial activity of a selection of new synthesized compounds were evaluated. The hybrid derivatives have an excellent solubility in microbiological medium, which make them promising from the pharmacological properties point of view. One of the hybrid compounds, 9 (with a benzimidazole and 8-aminoquinoline skeleton), exhibits a very good and selective antitumor activity against Renal Cancer A498 and Breast Cancer MDA-MB-468. Moreover, the anticancer assay suggests that the hybrid Imz (Bimz)/2-AP (8-AQ) compounds present a specific affinity to Renal Cancer A498. Concerning the antimycobacterial activity, only the hybrid compound, 9, has a significant activity. SAR correlations have been performed.

  14. 1-(4-Methylbenzyl-2-(4-methylphenyl-1H-benzimidazole

    Directory of Open Access Journals (Sweden)

    S. Rosepriya


    Full Text Available The title compound, C22H20N2, crystallizes with two independent molecules (A and B in the asymmetric unit. The benzimidazole units are almost planar [maximum deviations = 0.0161 (8 Å for A and 0.0276 (8 Å for B]. The dihedral angles between the benzimidazole unit and the benzene rings of the 4-methylbenzyl and 4-methylphenyl groups are 76.64 (3 and 46.87 (4°, respectively, in molecule A. The corresponding values in molecule B are 86.31 (2 and 39.14 (4°. The dihedral angles between the planes of the two benzene rings are 73.73 (3 and 80.69 (4° in molecules A and B, respectively. Pairs of weak intermolecular C—H...N hydrogen bonds link B molecules, forming centrosymmetric dimers with R22(8 ring motifs. There are no significant corresponding interactions involving the A molecules.

  15. Interaction of benzimidazole anthelmintics with Haemonchus contortus tubulin: binding affinity and anthelmintic efficacy. (United States)

    Lubega, G W; Prichard, R K


    The ability of various benzimidazoles (BZs) to bind tubulin under different conditions was assessed by determining their IC50 values (the concentration of unlabeled drug required to inhibit 50% of the labeled drug binding), Ka (the apparent equilibrium association constant) and Bmax (the maximum binding at infinite [BZ] = [drug-receptor]). The ability of unlabeled benzimidazoles--fenbendazole, mebendazole (MBZ), oxibendazole (OBZ), albendazole (ABZ), rycobendazole (albendazole sulfoxide, ABZSO), albendazole sulfone, oxfendazole (OFZ), and thiabendazole--to bind tubulin was determined from their ability to inhibit the binding of [3H]MBZ or [3H]OBZ to tubulin in supernatants derived from unembryonated eggs or adult worms of Haemonchus contortus. The binding constants (IC50, Ka, and Bmax) correlated with the known anthelmintic potency (recommended therapeutic doses) of the BZ compounds except for OFZ and ABZSO whose Ka values were lower than could be expected from anthelmintic potency. The binding of [3H]ABZ or [3H]OFZ to tubulin in supernatants derived from BZ-susceptible and BZ-resistant H. contortus was compared. [3H]ABZ demonstrated saturable high-affinity binding but [3H]OFZ bound with low affinity. The high-affinity binding of [3H]ABZ was reduced for the R strain. Tubulin bound BZ drugs at 4 degrees C with lower apparent Ka than at 37 degrees C.

  16. Treatment of Toxocara canis infections in mice with liposome-incorporated benzimidazole carbamates and immunomodulator glucan. (United States)

    Hrckova, G; Velebný, S


    Benzimidazole carbamates (mebendazole, albendazole and fenbendazole) are the most commonly used anthelmintic drugs for the treatment of larval toxocariasis (Toxocara canis) in paratenic hosts. However, the bioavailability of these drugs for tissues is very low due to their extremely low solubility, resulting in the administration of relatively high doses over a long period. To overcome this problem, neutral, negatively or positively charged and stabilized liposome drug carriers were examined in the chronic phase of T. canis infections in mice each orally inoculated with 1000 eggs. Moreover, liposomized albendazole and fenbendazole were co-administered with liposomized immunomodulator glucan. The highest efficacy of both drugs, evaluated 4 weeks after treatment, was recorded after their subcutaneous administration (ten doses of 25 mg kg(-1)) in stabilized liposomes and intramuscular co-administration of liposomized glucan (two doses of 5 mg kg(-1)). Fenbendazole was more effective in muscles (91.5%) whereas albendazole was more effective in the brain (92.2%). Liposomes with incorporated benzimidazole carbamate anthelmintics provide sustained drug-release reservoirs and can considerably enhance drug efficacy. Moreover, despite suppression by T. canis antigens, stimulation of the immune system by the immunomodulator glucan potentiates the effects of these antiparasitic drugs.

  17. Anticancer copper pyridine benzimidazole complexes: ROS generation, biomolecule interactions, and cytotoxicity. (United States)

    Prosser, Kathleen E; Chang, Stephanie W; Saraci, Felix; Le, Phuc H; Walsby, Charles J


    The Cu(II) complex CuCl2(pbzH), pbzH=2-(2-pyridyl)benzimidazole, and derivatives modified at the non-coordinated nitrogen of the benzimidazole fragment, have been studied as anticancer agents. These compounds show promising cytotoxicity against A549 adenocarcinomic alveolar basal epithelial cells with IC50 values in the range of 5-10μM. Importantly, this activity is higher than either CuCl2·2H2O or the individual ligands, demonstrating that ligand coordination to the Cu(II) centres of the complexes is required for full activity. Electron paramagnetic resonance (EPR) and UV-Vis spectroscopies were used to characterize the solution behaviour of the complexes. These studies demonstrate: (i) two types of solvated species in buffer, (ii) both coordinate and non-coordinate interactions with albumin, and (iii) weak interactions with DNA. Further DNA studies using agarose gel electrophoresis demonstrate strand cleavage by the complexes in the presence of ascorbate, which is mediated by reactive oxygen species (ROS). Through a fluorescence-based in vitro assay, intracellular ROS generation in the A549 cell line was observed; indicating that damage by ROS is responsible for the observed activity of the complexes.

  18. 5-Chloro-1-nonyl-1H-benzimidazol-2(3H-one

    Directory of Open Access Journals (Sweden)

    Youssef Kandri Rodi


    Full Text Available The asymmetric unit of the title compound, C16H23ClN2O, comtains two independent molecules in which the fused-ring systems are essentially planar, the largest deviation from the mean plane of each molecule being 0.011 (2 Å and 0.016 (2 Å. The benzimidazole rings of the two molecules make a dihedral angle of 66.65 (7°. The nonyl substituents are almost perpendicular to the benzimidazole planes [C—N—C—C tosrsion angles = 96.0 (3 and 81.0 (2°]. In the crystal, each independent molecule forms an inversion dimer via a pair of N—H...O hydrogen bonds. In one of the independent molecules, the terminal –CH2–CH3 group of the alkyl chain is disordered over two sets of sites with a refined occupancy ratio of 0.746 (7:0.254 (7.

  19. Design of benzimidazole- and benzoxazole-2-thione derivatives as inhibitors of bacterial hyaluronan lyase. (United States)

    Braun, Stephan; Botzki, Alexander; Salmen, Sunnhild; Textor, Christian; Bernhardt, Günther; Dove, Stefan; Buschauer, Armin


    Bacterial hyaluronan lyases (Hyal) degrade hyaluronan, an important component of the extracellular matrix, and are involved in microbial spread. Hyal inhibitors may serve as tools to study the role of the enzyme, its substrates and products in the course of bacterial infections. Moreover, such enzyme inhibitors are potential candidates for antibacterial combination therapy. Based on crystal structures of Streptococcus pneumoniae Hyal in complex with a hexasaccharide substrate and with different inhibitors, 1-acylated benzimidazole-2-thiones and benzoxazole-2-thiones were derived as new leads for the inhibition of Streptococcus agalactiae strain 4755 Hyal. Structure-based optimization led to N-(3-phenylpropionyl)benzoxazole-2-thione, one of the most potent compounds known to date (IC(50) values: 24 μM at pH 7.4, 15 μM at pH 5). Among the 27 new derivatives, other N-acylated benzimidazoles and benzoxazoles are just as active at pH 7.4, but not at pH 5. The results support a binding mode characterized by interactions with residues in the catalytic site and with a hydrophobic patch.

  20. Synthesis, structural and spectroscopic studies of two new benzimidazole derivatives: A comparative study (United States)

    Saral, Hasan; Özdamar, Özgür; Uçar, İbrahim


    In the present work, structural and spectroscopic studies on 1-Methyl-2-(2‧-hydroxy-4‧-chlorophenyl)benzimidazole (1) and 1-Methyl-2-(2‧-hydroxy-4‧-methoxyphenyl)benzimidazole (2), have been carried out extensively by X-ray diffraction, HRMS, UV-Vis, FT-IR and 1H and 13C NMR spectroscopy. The crystal structure of both compounds is stabilized by Osbnd H⋯N hydrogen bond and π-π interactions. Contrary to compound 1, the skeleton of compound 2 is considerably deviated from the planarity probably caused by intermolecular hydrogen bonding. The experimental results were compared to the theoretical ones, obtained at DFT level. Ground state geometry, electronic structure, vibrational and NMR spectra have been performed using the B3LYP functional with the 6-31 G(d,p) basis set. It was observed that the bond distances and angles in the both compounds were in good with those of the experiment. The energetic behaviors of the both compounds in methanol solvent were examined using by time-dependent DFT (TD-DFT) method by applying the polarizable continuum model (PCM). Isotropic chemical shifts (13C and 1H NMR) were calculated using the gauge-invariant atomic orbital (GIAO) method. The HOMO and LUMO analyses were used to elucidate information regarding charge transfer within the molecule.

  1. Sequence variation in the Trichuris trichiura beta-tubulin locus: implications for the development of benzimidazole resistance. (United States)

    Bennett, A B; Anderson, T J C; Barker, G C; Michael, E; Bundy, D A P


    Benzimidazole resistance has evolved in a variety of organisms and typically results from mutations in the beta-tubulin locus at specific amino acid sites. Despite widespread treatment of human intestinal nematodes with benzimidazole drugs, there have been no unambiguous reports of resistance. However, since beta-tubulin mutations conferring resistance are generally recessive, frequencies of resistance alleles less than 30% would be difficult to detect on the basis of drug treatment failures. Here we investigate sequence variation in a 1079 bp segment of the beta-tubulin locus in the human whipworm Trichuris trichiura from 72 individual nematodes from seven countries. We did not observe any alleles with amino acid mutations indicative of resistance, and of 40 point mutations there were only four non-synonymous mutations all of which were singletons. Estimated effective population sizes are an order of magnitude lower than those from another nematode species in which benzimidazole resistance has developed (Haemonchus contortus). Both the lower diversity and reduced population sizes suggest that benzimidazole resistance is likely to evolve less rapidly in Trichuris than in trichostrongyle parasites of livestock. We observed moderate levels of population subdivision (Phi(ST)=0.26) comparable with that previously observed in Ascaris lumbricoides, and identical alleles were frequently found in parasites from different continents, suggestive of recent admixture. A particularly interesting feature of the data is the high nucleotide diversities observed in nematodes from the Caribbean. This genetic complexity may be a direct result of extensive admixture and complex history of human populations in this region of the world. These data should encourage (but not make complacent) those involved in large-scale benzimidazole treatment of human intestinal nematodes.

  2. Synthesis and quantitative structure activity relationship (QSAR) of arylidene (benzimidazol-1-yl)acetohydrazones as potential antibacterial agents. (United States)

    El-Kilany, Yeldez; Nahas, Nariman M; Al-Ghamdi, Mariam A; Badawy, Mohamed E I; El Ashry, El Sayed H


    Ethyl (benzimidazol-1-yl)acetate was subjected to hydrazinolysis with hydrazine hydrate to give (benzimidazol-1-yl)acetohydrazide. The latter was reacted with various aromatic aldehydes to give the respective arylidene (1H-benzimidazol-1-yl)acetohydrazones. Solutions of the prepared hydrazones were found to contain two geometric isomers. Similarly (2-methyl-benzimidazol-1-yl)acetohydrazide was reacted with various aldehydes to give the corresponding hydrazones. The antibacterial activity was evaluated in vitro by minimum inhibitory concentration (MIC) against Agrobacterium tumefaciens (A. tumefaciens), Erwinia carotovora (E. carotovora), Corynebacterium fascians (C. fascians) and Pseudomonas solanacearum (P. solanacearum). MIC result demonstrated that salicylaldehyde(1H-benzimidazol-1-yl)acetohydrazone (4) was the most active compound (MIC = 20, 35, 25 and 30 mg/L against A. tumefaciens, C. fascians, E. carotovora and P. solanacearum, respectively). Quantitative structure activity relationship (QSAR) investigation using Hansch analysis was applied to find out the correlation between antibacterial activity and physicochemical properties. Various physicochemical descriptors and experimentally determined MIC values for different microorganisms were used as independent and dependent variables, respectively. pMICs of the compounds exhibited good correlation (r = 0.983, 0.914, 0.960 and 0.958 for A. tumefaciens, C. fascians, E. carotovora and P. solanacearum, respectively) with the prediction made by the model. QSAR study revealed that the hydrophobic parameter (ClogP), the aqueous solubility (LogS), calculated molar refractivity, topological polar surface area and hydrogen bond acceptor were found to have overall significant correlation with antibacterial activity. The statistical results of training set, correlation coefficient (r and r (2)), the ratio between regression and residual variances (f, Fisher's statistic), the standard error of estimates and

  3. VO(acac)2 catalyzed condensation of o-phenylenediamine with aromatic carboxylic acids/aldehydes under microwave radiation affording benzimidazoles

    Institute of Scientific and Technical Information of China (English)

    Madhudeepa Dey; Krishnajyoti Deb; Siddhartha Sankar Dhar


    Vanadyl acetylacetonate, VO(acac)2, has been found to be very effective catalyst for synthesis of a variety of benzimidazoles under solvent-free condition. The methodology involves the exposure of a mixture of o-phenylenediamine and a selected aromatic carboxylic acid/aldehyde to microwave radiation without the use of any solvent or supporting agents. The benzimidazoles were obtained in quick time with high yields.

  4. In vitro susceptibilities of the AIDS-associated microsporidian Encephalitozoon intestinalis to albendazole, its sulfoxide metabolite, and 12 additional benzimidazole derivatives.


    Katiyar, S. K.; Edlind, T D


    Recent reports have described the successful treatment of Encephalitozoon intestinalis infection in AIDS patients with albendazole. However, this compound is rapidly metabolized in vivo to albendazole sulfoxide, and furthermore it is only 1 of about 15 commercially developed benzimidazole derivatives. To compare the activities of albendazole, albendazole sulfoxide, and other benzimidazoles, an in vitro system involving infection of green monkey kidney cell (E6) monolayers with E. intestinalis...

  5. Novel Nonsymmetrically p-Benzyl-Substituted (Benzimidazole N-Heterocyclic Carbene-Silver(I Acetate Complexes: Synthesis and Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Frauke Hackenberg


    Full Text Available Nonsymmetrically substituted N-heterocyclic carbene (NHC precursors 1a–d and 3a–d were synthesised by first reacting 1H-(benzimidazole with p-cyanobenzyl bromide to give 4-(1H-imidazole-1-ylmethylbenzonitrile (1 and 4-(1H-benzimidazole-1-ylmethylbenzonitrile (3 and afterwards introducing benzyl bromide, 1-(bromomethyl-4-methylbenzene, 1-(bromomethyl-4-methoxybenzene, and methyl 4-(bromomethylbenzoate. The NHC-silver(I acetate complexes (1-benzyl-3-(4-cyanobenzyl-2,3-dihydro-1H-imidazole-2-ylidene silver(I acetate (2a, (1-(4-cyanobenzyl-3-(4-methylbenzyl-2,3-dihydro-1H-imidazole-2-ylidene silver(I acetate (2b, (1-(4-cyanobenzyl-3-[4-(methoxycarbonylbenzyl]-2,3-dihydro-1H-imidazole-2-ylidene silver(I acetate (2c, (1-benzyl-3-(4-cyanobenzyl-2,3-dihydro-1H-benzimidazole-2-ylidene silver(I acetate (4a, (1-(4-cyanobenzyl-3-(4-methylbenzyl-2,3-dihydro-1H-benzimidazole-2-ylidene silver(I acetate (4b, (1-(4-cyanobenzyl-3-(4-methoxybenzyl-2,3-dihydro-1H-benzimidazole-2-ylidene silver(I acetate (4c, and (1-(4-cyanobenzyl-3-[4-(methoxycarbonylbenzyl]-2,3-dihydro-1H-benzimidazole-2-ylidene silver(I acetate (4d were yielded by reacting these NHC precursors with silver(I acetate. The silver(I acetate complex 4b was characterised by single crystal X-ray diffraction. Preliminary in vitro antibacterial studies against the Gram-positive bacteria Staphylococcus aureus and the Gram-negative bacteria Escherichia coli, using the Kirby-Bauer disc diffusion method, were carried out on the seven NHC-silver(I acetate complexes 2a–c and 4a–d. Also the IC50 values of these seven complexes were determined by an MTT-based assay against the human renal cancer cell line Caki-1. The complexes 2a–c and 4a–c revealed the following IC50 values, respectively, 25 (±1, 15 (±2, 5.4 (±0.8, 16 (±2, 7.1 (±1, 20 (±4, and 14 (±1 μM.

  6. A general method for tritium labelling of benzimidazole carbamates by catalytic exchange in dioxane solutions

    Energy Technology Data Exchange (ETDEWEB)

    Lacey, E. (Commonwealth Scientific and Industrial Research Organization, Glebe, NSW (Australia). Div. of Animal Health, McMaster Lab.); Dawson, M. (Sydney Univ. (Australia). Dept. of Pharmacy); Long, M.A.; Than, C. (New South Wales Univ., Kensington (Australia). School of Chemistry)


    Benzimidazole carbamates (BZCs) act as inhibitors of the tubulin-microtubule equilibria in eukaryotic organisms. Recently drug resistance to this class of compounds in helminth parasites has been shown to be due to a reduced ability of resistant tubulin to bind BZCs. In order to quantitate the nature of the tubulin-BZC interaction a general method for the specific tritium labelling of BZCs has been developed. The BZCs: mebendazole, oxfendazole, parbendazole, oxibendazole, albendazole and fenbendazole were labelled by catalytic exchange using palladium on calcium carbonate in pure dioxane at 60{sup 0}C under tritium gas. The position of label incorporation for tritiated albendazole was determined by tritium-NMR as the 4-position of benzimadazole nucleus. The yields for individual BZCs varied from 8 to 68% for a range of specific activity of 0.44 to 13.4 Ci/mmole. (author).

  7. Synthesis and antimicrobial activity of novel 2-substituted benzimidazole, benzoxazole and benzothiazole derivatives

    Directory of Open Access Journals (Sweden)

    Vikas S. Padalkar


    Full Text Available In an endeavor to find a new class of antimicrobial agents, a series of 2-(1H-benzimidazol-2-yl-5-(diethylaminophenol, 2-(1,3-benzoxazol-2-yl-5-(diethylaminophenol, 2-(1,3-benzothiazol-2-yl-5-(diethylaminophenol and their derivatives were synthesized starting from p-N,N-diethyl amino salicylaldehyde with different substituted o-phenylenediamine or o-aminophenol or o-aminothiophenol. The newly synthesized compounds were characterized by FT-IR, 1H NMR and LC–MS analysis. All compounds were evaluated for in vitro antibacterial activities against Escherichia coli and Staphylococcus aureus strains and in vitro antifungal activity against Candida albicans and Aspergillus niger strains by using serial dilution method. The antibacterial activities were expressed as the minimum inhibitory concentration (MIC in μg/mL.

  8. Efficient fluorescent deep-blue and hybrid white emitting devices based on carbazole/benzimidazole compound

    KAUST Repository

    Yang, Xiaohui


    We report the synthesis, photophysics, and electrochemical characterization of carbazole/benzimidazole-based compound (Cz-2pbb) and efficient fluorescent deep-blue light emitting devices based on Cz-2pbb with the peak external quantum efficiency of 4.1% and Commission Internationale dÉnclairage coordinates of (0.16, 0.05). Efficient deep-blue emission as well as high triplet state energy of Cz-2pbb enables fabrication of hybrid white organic light emitting diodes with a single emissive layer. Hybrid white emitting devices based on Cz-2pbb show the peak external quantum efficiency exceeding 10% and power efficiency of 14.8 lm/W at a luminance of 500 cd/m2. © 2011 American Chemical Society.

  9. Synthesis and biological evaluation of novel pyrimidine-benzimidazol hybrids as potential anticancer agents. (United States)

    Shao, Kun-Peng; Zhang, Xu-Yao; Chen, Peng-Ju; Xue, Deng-Qi; He, Peng; Ma, Li-Ying; Zheng, Jia-Xin; Zhang, Qiu-Rong; Liu, Hong-Min


    A series of pyrimidine-benzimidazol hybrids was synthesized and evaluated for anticancer activity on four human cancer cell lines including MCF-7, MGC-803, EC-9706 and SMMC-7721. Some of the synthesized compounds exhibited moderate to potent activity against MGC-803 and MCF-7. Among them, compounds 5a-b and 6a-b showed most effective activity. Compounds 5b and 6b were more cytotoxic than 5-fluorouracil against all tested four human cancer cell lines, with IC50 values ranging from 2.03 to 10.55 μM and 1.06 to 12.89 μM, respectively. Flow cytometry analysis demonstrated that treatment of MGC-803 with 6b led to cell cycle arrest at G2/M phase accompanied by an increase in apoptotic cell death.

  10. Synthesis of novel benzimidazole functionalized chiral thioureas and evaluation of their antibacterial and anticancer activities. (United States)

    Madabhushi, Sridhar; Mallu, Kishore Kumar Reddy; Vangipuram, Venkata Sairam; Kurva, Srinivas; Poornachandra, Y; Ganesh Kumar, C


    A small library of benzimidazole functionalized chiral thioureas was prepared starting from natural amino acids (S)-alanine, (S)-phenylalanine, (S)-valine and (S)-leucine and also their (R)-isomers and studied their antimicrobial activity against a various Gram-positive and Gram-negative bacterial strains. In this study, compounds 5g and 5j were found to exhibit good antibacterial activity against both Gram-positive and Gram-negative bacterial strains such as Staphylococcus aureus, Bacillus subtilis, Micrococcus luteus, Klebsiella planticola, Escherichia coli and Pseudomonas aeruginosa. In the cytotoxicity study, thioureas derived from non-natural amino acids 5a-l showed good activity against human cancer cell lines A549, MCF7, DU145, HeLa, and no cytotoxicity was observed with their antipodes 6a-l.

  11. Synthesis and characterization of 2-substituted benzimidazoles and their evaluation as anticancer agent (United States)

    Azam, Mohammad; Khan, Azmat Ali; Al-Resayes, Saud I.; Islam, Mohammad Shahidul; Saxena, Ajit Kumar; Dwivedi, Sourabh; Musarrat, Javed; Trzesowska-Kruszynska, Agata; Kruszynski, Rafal


    In this work, we report a series of benzimidazole derivatives synthesized from benzene-1,2-diamine and aryl-aldehydes at room temperature. The synthesized compounds have been characterized on the basis of elemental analysis and various spectroscopic studies viz., IR, 1H- and 13C-NMR, ESI-MS as well by X-ray single X-ray crystallographic study. Interaction of these compounds with CT-DNA has been examined with fluorescence experiments and showed significant binding ability. All the synthesized compounds have been screened for their antitumor activities against various human cancer cell lines viz., Human breast adenocarcinoma cell line (MCF-7), Human leukemia cell line (THP-1), Human prostate cancer cell lines (PC-3) and adenocarcinomic human alveolar basal epithelial cell lines (A-549). Interestingly, all the compounds showed significant anticancer activity.

  12. Synthesis, in vitro and in vivo antitumor and antiviral activity of novel 1-substituted benzimidazole derivatives. (United States)

    Shaker, Yasser M; Omar, Mohamed A; Mahmoud, Khaled; Elhallouty, Salwa M; El-Senousy, Waled M; Ali, Mamdouh M; Mahmoud, Abeer E; Abdel-Halim, Abeer H; Soliman, Saeed M; El Diwani, Hoda I


    A novel series of 5-nitro-1H-benzimidazole derivatives substituted at position 1 by heterocyclic rings was synthesized. Cytotoxicity and antiviral activity of the new compounds were tested. Compound 3 was more active than doxorubicin against A-549, HCT-116 and MCF-7. However, compound 3 showed no activity against human liver carcinoma Hep G-2 cell line. Compounds 9 and 17b (E) showed potency near to doxorubicin against the four cell lines. The acute toxicity of compound 9 on liver cancer induced in rats was determined in vivo. Interestingly, it showed restoration activity of liver function and pathology towards normal as compared to the cancer-bearing rats induced by DENA. Compounds 17a (Z), 17b (E) and 18a (Z) were the most promising compounds for their antiviral activity against rotavirus Wa strain.

  13. Synthesis of New Benzimidazole and Benzothiazole Disulfide Metal Complexes as G-quadruplex Binding Ligands. (United States)

    Saour, Kawkab; Lafta, Dunya


    Compounds that can bind and stabilize non-canonical DNA structures are named quadruplex and are of interest in anticancer drug design due to their selective inhibitions of telomerase and consequent effects on cell proliferation. In this study, we report novel Co/Cu [II] complex compounds as G-quadruplex DNA binding ligands. The results from the preliminary assay indicated that the introduction of a positively charged 6-membered tail to the aromatic terminal group of benzimidazole significantly enhanced the binding affinity with the quadruplex and exhibited anti-telomerase activity. These derivatives showed significant selectivities for the telomeric quadruplex over duplex nucleic acids. The stabilization of non-canonical forms estimated with the FRET DNA technology using different sequences, such as F21T, c-kit1 and c-kit2, in cancer cell lines were assessed. Three members of this family showed to be very selective in stabilizing one particular G-quadruplex.

  14. Synthesis and biological activity of some heterocyclic compounds containing benzimidazole and beta-lactam moiety

    Indian Academy of Sciences (India)

    K F Ansari; C Lal


    A number of 1-substituted-2-methyl benzimidazole derivatives have been synthesized and tested for their antibacterial activities. The chemical structures of the newly synthesized compounds were verified on the basis of spectral and elemental methods of analyses. Investigation of antimicrobial activity of the compounds was done by disc diffusion method using Gram-positive (S. aureus, S. mutans and B. subtilis), Gram-negative (E. coli, S. typhi and P. aeruginosa) bacteria and fungi (C. albicans, A. flavus and A. niger). Among the compounds tested 5a, 5b, 5d, 5i, 5j and 5k exhibited good antibacterial activities against Gram positive bacteria, while 5d and 5i also showed notable antifungal activity. Specially compounds 5a and 5b exhibited appreciable activity against S. aureus and B. subtilis comparable to reference drugs.

  15. Potent DGAT1 Inhibitors in the Benzimidazole Class with a Pyridyl-oxy-cyclohexanecarboxylic Acid Moiety. (United States)

    He, Shuwen; Hong, Qingmei; Lai, Zhong; Wu, Zhicai; Yu, Yang; Kim, David W; Ting, Pauline C; Kuethe, Jeffrey T; Yang, Ginger X; Jian, Tianying; Liu, Jian; Guiadeen, Deodial; Krikorian, Arto D; Sperbeck, Donald M; Sonatore, Lisa M; Wiltsie, Judyann; Chung, Christine C; Gibson, Jack T; Lisnock, JeanMarie; Murphy, Beth A; Gorski, Judith N; Liu, Jinqi; Chen, Dunlu; Chen, Xiaoli; Wolff, Michael; Tong, Sharon X; Madeira, Maria; Karanam, Bindhu V; Shen, Dong-Ming; Balkovec, James M; Pinto, Shirly; Nargund, Ravi P; DeVita, Robert J


    We report the design and synthesis of a series of novel DGAT1 inhibitors in the benzimidazole class with a pyridyl-oxy-cyclohexanecarboxylic acid moiety. In particular, compound 11A is a potent DGAT1 inhibitor with excellent selectivity against ACAT1. Compound 11A significantly reduces triglyceride excursion in lipid tolerance tests (LTT) in both mice and dogs at low plasma exposure. An in vivo study in mice with des-fluoro analogue 10A indicates that this series of compounds appears to distribute in intestine preferentially over plasma. The propensity to target intestine over plasma could be advantageous in reducing potential side effects since lower circulating levels of drug are required for efficacy. However, in the preclinical species, compound 11A undergoes cis/trans epimerization in vivo, which could complicate further development due to the presence of an active metabolite.

  16. A third polymorph of 1,4-bis(1H-benzimidazol-2-ylbenzene

    Directory of Open Access Journals (Sweden)

    Wei-Wei Fu


    Full Text Available The title compound, C20H14N4, is a new polymorph of the previously reported structures, which were orthorhombic, space group Pbca [Bei et al. (2000. Acta Cryst. C56, 718–719] and monoclinic, space group P21/c [Dudd et al. (2003. Green Chem. 5, 187–192]. The asymmetric unit consists of two independent molecules in which the dihedral angels between the central benzene ring and the outer benzimidazole ring systems are 16.81 (10 and 14.23 (10° in one molecule and 26.09 (10 and 37.29 (10° in the other. In the crystal, molecules are linked by N—H...N and C—H...N hydrogen bonds into a tape running along the c-axis direction.

  17. 5-Chloro-2-methylsulfanyl-6-(naphthalen-1-yloxy-1H-benzimidazole methanol monosolvate

    Directory of Open Access Journals (Sweden)

    Miguel Flores-Ramos


    Full Text Available In the title compound, C18H13ClN2OS·CH3OH, the dihedral angle between the benzimidazole group and the naphthyloxy moiety [82.89 (5°] very near to orthogonality. The H atom in the five-membered ring is disordered with equal occupancies at the two N atoms and the H atom of the methanolic hydroxy group is disordered with equal occupancies over two sites at the O atom. The methanol molecule acts as a hydrogen-bond acceptor for the amino H atom and donates a hydrogen bond to the nonprotonated ring N atom. As a result, chains are formed running along the a axis.

  18. Anthelmintic activity of benzimidazole derivatives against Toxocara canis second-stage larvae and Hymenolepis nana adults. (United States)

    Márquez-Navarro, Adrián; Nogueda-Torres, Benjamín; Hernández-Campos, Alicia; Soria-Arteche, Olivia; Castillo, Rafael; Rodríguez-Morales, Sergio; Yépez-Mulia, Lilián; Hernández-Luis, Francisco


    The anthelmintic activity of 11 benzimidazole derivatives (A1-A11) and 2 thioureides N,N'-disubstituted (B1-B2) was determined. Each compound and albendazole was tested in vitro against Toxocara canis larvae and in vivo against Hymenolepis nana adult. Compounds A1-A6 and B1-B2 were designed as albendazole prodrugs. Compounds A8-A11 were designed as direct analogues of A7, which had previously proved to be an effective agent against Fasciola hepatica. Results of the in vitro screening showed that A6 was more active than albendazole at 0.18 microM (relative mobility 40% and 80%, respectively). Whereas that the in vivo evaluation against H. nana, compounds A7-A11 demonstrated significant activity in terms of removing cestode adults in the range of 88-97%, displaying better efficacy than albendazole (83%).

  19. 2-(Thiophen-2-yl-1-(thiophen-2-ylmethyl-1H-benzimidazole

    Directory of Open Access Journals (Sweden)

    David K. Geiger


    Full Text Available In the title compound, C16H12N2S2, the thiophene groups are rotationally disordered over two sets of sites, by approximately 180°, with occupancy ratios of 0.916 (2:0.084 (2 and 0.903 (2:0.097 (2. The major components of the thiophene and methylene substituted thiophene rings are canted by 24.06 (12 and 85.07 (10°, respectively, from the benzimidazole ring system plane and the dihedral angle between the major component thiophene ring planes is 84.90 (14°. In the crystal, there is a weak C—H...N hydrogen bond which links molecules into chains.

  20. Solubility improvement of an anthelmintic benzimidazole carbamate by association with dendrimers

    Energy Technology Data Exchange (ETDEWEB)

    Fernandez, L.; Sigal, E.; Santo, M., E-mail: [Departamento de Fisica, Facultad de Ciencias Exactas Fisicoquimicas y Naturales, Universidad Nacional de Rio Cuarto (Argentina); Otero, L.; Silber, J. J. [Departamento de Quimica. Facultad de Ciencias Exactas Fisicoquimicas y Naturales, Universidad Nacional de Rio Cuarto, Rio Cuarto (Argentina)


    The improvement of aqueous solubility of methyl (5-[propylthio]-1H-benzimidazole-2-yl) carbamate, albendazole (ABZ) using polyamidoamine (PAMAM) dendrimers as solubility enhancers was investigated. Full generation PAMAM dendrimers with amine terminal groups, (G3), with hydroxyl terminal groups (G3OH) and half generation PAMAM dendrimers with carboxylate terminal groups (G2.5 and G3.5), were chosen for this study. The nature of dendrimer-ABZ association was investigated by UV absorption, fluorescence emission measurements and by {sup 1}H-NMR spectroscopy. The results obtained show that these polymeric structures have the capacity to enhance the solubility of ABZ, both lipophilic and specific hydrogen bond interactions contributing to the guest-host association. Although all studied dendrimers have hydrophobic internal nanoenvironments with similar dimensions, their surfaces differ significantly and the nature and the localization of the interactions involved in ABZ-dendrimer association depend on the type of terminal groups. (author)

  1. 2-(2{prime}-hydroxyphenyl)benzothiazoles, -benzoxazoles, and -benzimidazoles for plastic scintillation applications

    Energy Technology Data Exchange (ETDEWEB)

    Pla-Dalmau, A. [Fermi National Accelerator Lab., Batavia, IL (United States)


    A new series of fluorescent compounds has been tested as dopants for plastic scintillation applications. Several 2-(2{prime}-hydroxyphenyl)benzothiazole, -benzoxazole, and -benzimidazole derivatives have been prepared and studied in a polystyrene matrix. Each derivative has been added to a styrene solution which has been thermally polymerized. The transmittance, fluorescence, and light yield characteristics of these compounds in polystyrene have been determined. Their emission time distributions have also been measured, and the decay time constants have been calculated from these data. In addition, the doped polystyrene samples have been irradiated to a total dose of 10 Mrad, utilizing a {sup 60}Co source in order to evaluate their susceptibility to radiation-induced damage. 6 figs., 1 tab.

  2. Benzimidazole-1,2,3-triazole hybrid molecules: synthesis and evaluation for antibacterial/antifungal activity. (United States)

    Ouahrouch, Abdelaaziz; Ighachane, Hana; Taourirte, Moha; Engels, Joachim W; Sedra, My Hassan; Lazrek, Hassan B


    A novel series of hybrid molecules 4a-i and 5a-i were prepared by condensation of 4-(trimethylsilylethynyl)benzaldehyde 1 with substituted o-phenylenediamines. These in turn were reacted with 2-(azidomethoxy)ethyl acetate in a Cu alkyne-azide cycloaddition (CuAAC) to generate the 1,2,3-triazole pharmacophore under microwave assistance. The newly synthesized compounds were examined for their in vitro antimicrobial activities against Gram-positive and Gram-negative bacteria and the phytopathogenic fungi Verticillium dahliae and Fusarium oxysporum f. sp. albedinis. 2-((4-(4-(5-Trifluoromethyl benzimidazol-2-yl)phenyl)-1,2,3-triazol-1-yl)methoxy)ethanol 5e showed a moderate inhibition of 30% in the Foa sporulation test.

  3. Polymer Electrolyte Membrane Fuel Cell Performance of a Sulfonated Poly(Arylene Ether Benzimidazole Copolymer Membrane

    Directory of Open Access Journals (Sweden)

    Hasan Ferdi Gerçel


    Full Text Available Disodium-3,3′-disulfonate-4,4′-dichlorodiphenylsulfone (SDCDPS and 5,5′-bis[2-(4-hydroxyphenylbenzimidazole] (HPBI monomers were synthesized. Binding these monomers via nucleophilic aromatic polycondensation reaction, a sulfonated poly(arylene ether benzimidazole copolymer was synthesized. Structures of monomers and copolymer were confirmed by proton nuclear magnetic resonance spectroscopy (1H NMR and Fourier transform infrared (FTIR spectroscopy analyses. Proton exchange membrane was prepared by dissolving copolymer in dimethylacetamide (DMAc and casting onto a glass plate. Copolymer membrane was doped with sulfuric acid to ensure proton exchange character. Single cell performance of the copolymer membrane was tested in a polymer electrolyte membrane fuel cell test station. The highest power density of the membrane was measured as 23.7 mW cm−2 at 80°C. Thermogravimetric analysis (TGA showed that as the degree of disulfonation is increased thermal stability of the copolymer is increased.

  4. Activation of peroxyl and molecular oxygen using bis-benzimidazole diamide copper (II) compounds

    Indian Academy of Sciences (India)

    Pavan Mathur


    New tetradentate bis-benzimidazole ligands have been synthesized and utilized to prepare copper (II) complexes. Some of these copper (II) complexes have been characterized structurally. The copper (II) in these complexes is found to possess varying geometries. A distorted octahedral geometry is found with a highly unsymmetrical bidentate nitrate group. An unusual polymeric one-dimensional structure is observed where copper (II) is in a distorted square pyramidal geometry with a monodentate nitrate ion, having long Cu-O bond, while a distorted triagonal bipyramidal geometry is found with two carbonyl O atoms and a Cl atom in the equatorial plane, and two benzimidazole imine N atoms occupy the axial position. These compounds are found to activate the cumylperoxyl group, and this has been utilized in the facile oxidation of aromatic alcohols to aldehydes, where they act as catalysts with large turnovers. The yields of the respective products vary from 32 to 65%. The role of molecular oxygen has been studied and an attempt has been made to identify the "active copper species”. Activation of molecular oxygen has also been observed and has been used for oxidative dealkylation of a hindered phenol, producing di-butyl quinones with yields of 20-25% and 10-12 fold catalytic turnover. Dihydroxybenzenes and substituted catechols are also readily oxidized to the corresponding quinones, in oxygen-saturated solvents. Yields of 84% have been observed with 34-fold catalyst turnover, with di--butylcatechol. The activity of these copper (II) - bis-benzmidazolediamide compounds is reminiscent of the functioning of copper centres in galactose oxidase, tyrosinase and catechol oxidase.

  5. Design and synthesis of benzimidazole analogs endowed with oxadiazole as selective COX-2 inhibitor. (United States)

    Rathore, Ankita; Rahman, Mujeeb Ur; Siddiqui, Anees Ahamad; Ali, Abuzer; Shaharyar, Mohammad


    New molecules of benzimidazole endowed with oxadiazole were designed and synthesized from 2-(2-((pyrimidin-2-ylthio)methyl)-1H-benzo[d]imidazol-1-yl)acetohydrazide as 1-((5-substituted alkyl/aryl-1,3,4-oxadiazol-2-yl)methyl)-2-((pyrimidin-2-ylthio)methyl)-1H-benzimidazoles (5a-r) with the aim to acquire selective cyclooxygenase (COX-2) inhibitor activity. The synthesized compounds were screened by in vitro cyclooxygenase assays to determine COX-1 and COX-2 inhibitory potency and the results showed that they had good-to-remarkable activity with an IC50 range of 11.6-56.1 µM. The most active compounds were further screened for their in vivo anti-inflammatory activity by using the carrageenan-induced rat paw edema model. In vitro anticancer activities of the hybrid compounds were assessed by the National Cancer Institute (NCI), USA, against 60 human cell lines, and the results showed a good spectrum. Compound 5l exhibited significant COX-2 inhibition with an IC50 value of 8.2 µM and a percent protection of 68.4%. Compound 5b evinced moderate cytotoxicity toward the UO-31 cell line of renal cancer. A docking study was performed using Maestro 9.0, to provide the binding mode into the binding sites of the cyclooxygenase enzyme. Hopefully, in the future, compound 5l could serve as a lead compound for developing new COX-2 inhibitors.

  6. The effectiveness of benzimidazole derivatives for the treatment and prevention of histomonosis (blackhead) in turkeys. (United States)

    Hegngi, F N; Doerr, J; Cummings, T S; Schwartz, R D; Saunders, G; Zajac, A; Larsen, C T; Pierson, F W


    The benzimidazole derivatives, albendazole and fenbendazole were evaluated for their effectiveness in the treatment and prevention of histomonosis (blackhead) in turkeys. Histomonosis was produced in 5 week-old birds by placing them on broiler breeder litter known to be contaminated with Heterakis gallinae ova and the protozoan Histomonas meleagridis. In the first trial, at the onset of confirmed clinical disease, birds were treated orally with metronidazole, a compound known to be effective against Histomonas. Those receiving metronidazole had significantly greater mean body weight gains during the treatment period and the 2 weeks following treatment than untreated controls. Treated birds also had significantly lower caecal and liver lesion scores. These findings served to validate the method of disease reproduction and establish its suitability for testing the benzimidazoles. Similar trials were conducted to determine the therapeutic value of albendazole at 100.0 mg/kg of body weight and fenbendazole at 10.0 mg/kg body weight, administered orally twice a day for 5 consecutive days. Under these conditions, both drugs were found to be ineffective as treatments. A final trial was conducted to assess the prophylactic value of albendazole and fenbendazole administration. At the time of placement on contaminated litter, birds were medicated as previously described with the exception that treatment was continued for 14 consecutive days, the approximate incubation period for histomonosis. The trial was terminated on the 16th day. In the case of both albendazole and fenbendazole, treatment was associated with a significant increase in mean body weight gain and lower caecal and liver lesion scores. It is believed that the observed prophylactic effect may be attributed to the destruction of the transport vector e.g., Heterakis larvae, or to direct killing of the flagellated form of Histomonas which is normally found in the caecal lumen and is considered to be more sensitive

  7. Comparative plasma disposition kinetics of albendazole and its new benzimidazol prodrug in dog. (United States)

    Khalil, Z; El Karbane, M; Faouzi, M E A; Ansar, M; Azougagh, M; El Harti, J; Taoufik, J


    The comparative pharmacokinetic behavior of albendazole (ABZ) and its new benzimidazol prodrug [1-tert-butyloxycarbonyl-5-propylthio-1-H-benzimidazol-2ylcarbamate of methyl] (ABZBoc), following their oral administration (10mg/kg) to healthy dogs was explored. Blood samples were obtained serially over a 24h period after treatment, then the plasma was analyzed by high-performance liquid chromatography (HPLC) to search the albendazole metabolites (ABZSO and ABZSO2). However, the albendazole parent drug was not detectable at any time after both treatments (ABZ and ABZBoc). By albendazole metabolites (ABZSO and ABZSO2) were the analytes recovered in the plasma after oral administration of ABZ and ABZBoc. Furthermore, some amounts of ABZBoc were also available in the plasma samples treated with this new produg. The plasma profile of each analyte followed a similar pattern after both treatments, the active metabolite (ABZSO) was the major analyte recovered in plasma (between 1 and 24h post-treatment). The pharmacokinetic parameters of both groups were calculated (Cmax, Tmax, t1/2, AUC0-›∞), and analyzed using the Student's t-test, Palbendazole metabolites (ABZSO, ABZSO2) between the group treated with albendazole (group A) and that treated with ABZBoc prodrug (group B). Hence, the levels of the various pharmacokinetics parameters were low in the group treated with prodrug, as well they did not reach equivalent concentrations to that of albendazole. These differences between albendazole and its new prodrug may be explained by the fact that ABZBoc prodrug was not effectively reduced in the intestine of dogs.

  8. Optimization of Phenyl-Substituted Benzimidazole Carboxamide Poly(ADP-Ribose) Polymerase Inhibitors: Identification of (S)-2-(2-Fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (A-966492), a Highly Potent and Efficacious Inhibitor

    Energy Technology Data Exchange (ETDEWEB)

    Penning, Thomas D.; Zhu, Gui-Dong; Gong, Jianchun; Thomas, Sheela; Gandhi, Viraj B.; Liu, Xuesong; Shi, Yan; Klinghofer, Vered; Johnson, Eric F.; Park, Chang H.; Fry, Elizabeth H.; Donawho, Cherrie K.; Frost, David J.; Buchanan, Fritz G.; Bukofzer, Gail T.; Rodriguez, Luis E.; Bontcheva-Diaz, Velitchka; Bouska, Jennifer J.; Osterling, Donald J.; Olson, Amanda M.; Marsh, Kennan C.; Luo, Yan; Giranda, Vincent L. (Abbott)


    We have developed a series of phenylpyrrolidine- and phenylpiperidine-substituted benzimidazole carboxamide poly(ADP-ribose) polymerase (PARP) inhibitors with excellent PARP enzyme potency as well as single-digit nanomolar cellular potency. These efforts led to the identification of (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (22b, A-966492). Compound 22b displayed excellent potency against the PARP-1 enzyme with a K{sub i} of 1 nM and an EC{sub 50} of 1 nM in a whole cell assay. In addition, 22b is orally bioavailable across multiple species, crosses the blood-brain barrier, and appears to distribute into tumor tissue. It also demonstrated good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination with temozolomide and in an MX-1 breast cancer xenograft model both as a single agent and in combination with carboplatin.

  9. Expeditious and Efficient Synthesis of Benzoxazoles, Benzothiazoles, Benzimidazoles Catalyzed by Ga(OTf)3 under Solvent-Free Conditions%Expeditious and Efficient Synthesis of Benzoxazoles, Benzothiazoles, Benzimidazoles Catalyzed by Ga(OTf)3 under Solvent-Free Conditions

    Institute of Scientific and Technical Information of China (English)

    刘巨艳; 刘倩; 徐玮; 王玮璐


    A new and efficient method for the synthesis of benzoxazoles, benzothiazoles, benzimidazoles from reactions of o-substituted aminoaromatics with orthoesters in the presence of catalytic amounts of Ga(OTf)3 under solvent-free conditions is presented. The remarkable features of this new protocol are high conversion, very short reaction times, cleaner reaction profiles under solvent-free conditions, straight forward procedure, and use of relatively non-toxic catalysts.

  10. Synthesis and Biological Evaluation of Novel Benzimidazole Derivatives Bearing a Heterocyclic Ring at 4/5 Position

    Energy Technology Data Exchange (ETDEWEB)

    Wubulikasimu, Reyila; Yang, Yanbing; Xue, Fei; Luo, Xianjin; Shao, Dongping [Shanghai Jiaotong Univ., Shanghai (China); Li, Yuhuan; Gao, Rongmei [Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Ye, Weidong [Zhejiang Medicine Co. Ltd., Zhejiang (China)


    A series of novel benzimidazole derivatives bearing a heterocyclic ring as oxadiazole (21-32), thiadiazole (33-34), triazole (35-36) were synthesized and evaluated for their activities against Coxsackie virus B3 and B6 in Vero cells. Compounds 21-26, 31-36 with moieties of 2'-pyridyl, 3'-pyridyl and 4'-pyridyl at the 2-position and oxadiazoles, thiadiazole, or triazole substituent at the 4- or 5-position generally displayed activities against CVB3 and CVB6. Especially compound 24 (IC{sub 50} = 1.08 μg/mL, SI = 61.7 against CVB3) was the promising candidate as lead compound for anti-enteroviral drug. It was observed in the incorporation of heterocyclic rings in benzimidazole at the 5-position could enhance their biological activities.

  11. Two thiazolylindoles and a benzimidazole: novel compounds on the designer drug market with potential cannabinoid receptor activity. (United States)

    Westphal, Folker; Sönnichsen, Frank D; Knecht, Siegfried; Auwärter, Volker; Huppertz, Laura


    In a seizure of German customauthorities two 3-([1,3]-thiazol-2-yl)indoles (N-(2-methoxyethyl),N-iso-propyl-2-(1-pentyl-1H-indol-3-yl)-4-thiazolemethanamine (1) and N,N-diethyl-2-(1-pentyl-1H-indol-3-yl)-4-thiazolemethanamine (2)) and one benzimidazole (1-(cyclohexylmethyl)-2-[(4-ethoxyphenyl)methyl]-N,N-diethyl-1H-benzimidazole-5-carboxamide (6)) were seized as pure compounds. The compounds have been detected in Germany for the first time, and no analytical data had been previously published. Mass spectrometric (MS), infrared (IR) spectroscopic, and nuclear magnetic resonance (NMR) spectroscopic data are presented and the way of the structure elucidation of these rather uncommon compounds is discussed.

  12. Nanostructures and Self-Assembly of Organogels via Benzimidazole/Benzothiazole Imide Derivatives with Different Alkyl Substituent Chains

    Directory of Open Access Journals (Sweden)

    Xihai Shen


    Full Text Available New benzimidazole/benzothiazole imide derivatives with different alkyl substituent chains were designed and synthesized. Their gelation behaviors in 22 solvents were tested as novel low-molecular-mass organic gelators. The test showed that the alkyl substituent chains and headgroups of benzimidazole/benzothiazole residues in gelators played a crucial role in the gelation behavior of all compounds in various organic solvents. More alkyl chains in molecular skeletons in present gelators are favorable for the gelation of organic solvents. SEM and AFM observations revealed that the gelator molecules self-assemble into different aggregates from wrinkle, lamella and belt to dot with change of solvents. Spectral studies indicated that there existed different H-bond formation between imide groups and hydrophobic force of alkyl substituent chains in molecular skeletons. The present work may give some insights into design and character of new organogelators and soft materials with special molecular structures.

  13. Structure of HIV-1 nonnucleoside reverse transcriptase inhibitors derivatives of N-benzyl-benzimidazole with different substituents in position 4 (United States)

    Ziółkowska, Natasza E.; Michejda, Christopher J.; Bujacz, Grzegorz D.


    The constant development of new drugs against HIV-1 is necessary due to global expansion of AIDS and HIV-1 drug resistance. Nonnucleoside reverse transcriptase inhibitors of HIV-1 (NNRTIs) are potentially effective and nontoxic drugs in AIDS therapy. The crystal structures of six nonnucleoside inhibitors of HIV-1 reverse transcriptase (RT) derivatives of N-benzyl-benzimidazole are reported here. The investigated compounds belong to the group of so called "butterfly like" inhibitors with characteristic two π-electron moieties with an angled orientation. The structural data show the influence of the substituents of the benzimidazole ring on the geometry of the molecule and correlation between the structure of the inhibitor and its biological activity.

  14. Synthesis, photo-physical and DFT studies of ESIPT inspired novel 2-(2',4'-dihydroxyphenyl) benzimidazole, benzoxazole and benzothiazole. (United States)

    Patil, Vikas S; Padalkar, Vikas S; Tathe, Abhinav B; Gupta, Vinod D; Sekar, N


    Novel ESIPT inspired benzimidazole, benzoxazole and benzothiazole were synthesized from 2,4-dihydroxy benzoic acid and 1,2-phenelenediamine, 2-aminophenol, and 2-aminothiophenol respectively. The synthesized 2-(2',4'-dihydroxyphenyl) benzimidazole, benzoxazole and benzothiazole are fluorescent and the emission characteristic are very sensitive to the micro-environment. They show a single absorption and dual emission with large Stokes shift originating from excited state intramolecular proton transfer. The absorption-emission characteristics of all these compounds are studied as a function of pH. The change in the electronic transition, energy levels, and orbital diagrams of synthesized compounds were investigated by the molecular orbital calculation and were correlated with the experimental spectral emission. Experimental absorption and emission wavelengths are in good agreement with those predicted using the Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TD-DFT) [B3LYP/6-31G(d)].

  15. Crystal structure of {bis[(1H-benzimidazol-2-yl-κN3methyl]sulfane}dichloridomercury(II

    Directory of Open Access Journals (Sweden)

    Mehdi Bouchouit


    Full Text Available In the asymmetric unit of the title compound, [HgCl2(C16H14N4S], the HgII cation is linked to two Cl atoms and two imidazole N atoms of the chelating bis[(1H-benzimidazol-2-ylmethyl]sulfane ligand, forming a slightly distorted tetrahedral environment. The substitued imidazole rings of the ligand are almost perfectly planar [with maximum deviations of 0.017 (3 and 0.012 (3 Å] and form a dihedral angle of 42.51 (5°. The crystal packing can be described as alternating layers parallel to (010. In this arrangement, N—H...Cl hydrogen bonds between the N—H groups of the benzimidazole moieties and chloride ligands are responsible for the formation of the chain-like packing pattern along [010] exhibiting a C(6 graph-set motif.

  16. 1-Benzyl-2-Phenylbenzimidazole (BPB, a Benzimidazole Derivative, Induces Cell Apoptosis in Human Chondrosarcoma through Intrinsic and Extrinsic Pathways

    Directory of Open Access Journals (Sweden)

    Ju-Fang Liu


    Full Text Available In this study, we investigated the anticancer effects of a new benzimidazole derivative, 1-benzyl-2-phenyl -benzimidazole (BPB, in human chondrosarcoma cells. BPB-mediated apoptosis was assessed by the MTT assay and flow cytometry analysis. The in vivo efficacy was examined in a JJ012 xenograft model. Here we found that BPB induced apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 but not in primary chondrocytes. BPB induced upregulation of Bax, Bad and Bak, downregulation of Bcl-2, Bid and Bcl-XL and dysfunction of mitochondria in chondrosarcoma. In addition, BPB also promoted cytosolic releases AIF and Endo G. Furthermore, it triggered extrinsic death receptor-dependent pathway, which was characterized by activating Fas, FADD and caspase-8. Most importantly, animal studies revealed a dramatic 40% reduction in tumor volume after 21 days of treatment. Thus, BPB may be a novel anticancer agent for the treatment of chondrosarcoma.

  17. One step synthesis of pyrido[1,2-α]benzimidazole derivatives of aryloxypyrazole and their antimicrobial evaluation

    Institute of Scientific and Technical Information of China (English)

    Hardik H.Jardosh; Chetan B.Sangani; Manish P.Patel; Ranjan G.Patel


    A new series of pyrido[1,2-α]benzimidazole derivatives bearing the aryloxypyrazole nucleus have been synthesized by base-catalyzed cyclocondensation reaction through multi-component reaction (MCR) approach.All the synthesized compounds were investigated against a representative panel of pathogenic strains using broth microdilution minimum inhibitory concentration (MIC) method for their in vitro antimicrobial activity.Reviewing the data,majority of the compounds were found to be active against employed pathogens.SAR study explores that antimicrobial activity is strongly depends on the nature of the substituents at the ether linked aryl ring attached to the pyrazole unit,together with the substituent present on the C5 of the benzimidazole unit.

  18. A benzimidazole derivative exhibiting antitumor activity blocks EGFR and HER2 activity and upregulates DR5 in breast cancer cells. (United States)

    Chu, B; Liu, F; Li, L; Ding, C; Chen, K; Sun, Q; Shen, Z; Tan, Y; Tan, C; Jiang, Y


    Aberrant expression or function of epidermal growth factor receptor (EGFR) or the closely related human epidermal growth factor receptor 2 (HER2) can promote cell proliferation and survival, thereby contributing to tumorigenesis. Specific antibodies and low-molecular-weight tyrosine kinase inhibitors of both proteins are currently in clinical trials for cancer treatment. Benzimidazole derivatives possess diverse biological activities, including antitumor activity. However, the anticancer mechanism of 5a (a 2-aryl benzimidazole compound; 2-chloro-N-(2-p-tolyl-1H-benzo[d]imidazol-5-yl)acetamide, C(16)H(14)ClN(3)O, MW299), a novel 2-aryl benzimidazole derivative, toward breast cancer is largely unknown. Here, we demonstrate that 5a potently inhibited both EGFR and HER2 activity by reducing EGFR and HER2 tyrosine phosphorylation and preventing downstream activation of PI3K/Akt and MEK/Erk pathways in vitro and in vivo. We also show that 5a inhibited the phosphorylation of FOXO and promoted FOXO translocation from the cytoplasm into the nucleus, resulting in the G1-phase cell cycle arrest and apoptosis. Moreover, 5a potently induced apoptosis via the c-Jun N-terminal kinase (JNK)-mediated death receptor 5 upregulation in breast cancer cells. The antitumor activity of 5a was consistent with additional results demonstrating that 5a significantly reduced tumor volume in nude mice in vivo. Analysis of the primary breast cancer cell lines with HER2 overexpression further confirmed that 5a significantly inhibited Akt Ser473 and Bad Ser136 phosphorylation and reduced cyclin D3 expression. On the basis of our findings, further development of this 2-aryl benzimidazole derivative, a new class of multitarget anticancer agents, is warranted and represents a novel strategy for improving breast cancer treatment.

  19. NaHSO4-SiO2-Promoted Solvent-Free Synthesis of Benzoxazoles, Benzimidazoles, and Benzothiazole Derivatives

    Directory of Open Access Journals (Sweden)

    K. Ravi Kumar


    Full Text Available An efficient protocol has been developed for the preparation of a library of benzoxazole, benzimidazole, and benzothiazole derivatives from reactions of acyl chlorides with o-substituted aminoaromatics in the presence of catalytic amount of silica-supported sodium hydrogen sulphate under solvent-free conditions. Simple workup procedure, high yield, easy availability, reusability, and use of ecofriendly catalyst are some of the striking features of the present protocol.

  20. Synthesis and anticancer activity of novel benzimidazole and benzothiazole derivatives against HepG2 liver cancer cells. (United States)

    Youssef, Amal M; Malki, Ahmed; Badr, Mona H; Elbayaa, Rasha Y; Sultan, Ahmed S


    Most of cancer chemotherapeutics and chemopreventives exert their effects by triggering apoptotic cell death. In this study, novel benzimidazole and benzothiazole derivatives have been synthesized to investigate their effects on HepG2 liver cancer cell lines after initial screening study. A dose response curve was constructed and the most active derivatives were further studied for apoptotic analysis. Six active benzimidazole derivatives (8, 9, 10, 12, 13 and 14) significantly induced apoptosis compared to control group. Two compounds 10 and 12 induced apoptosis by arresting cells in G1 phase of cell cycle which is confirmed by increased expression level of p21. The activity of caspase-3 which is well known as one of the key executioners of apoptosis was determined in the presence and absence of the tested derivatives. Our results indicated that compounds 10 and 12 significantly increased caspase-3 activity compared to control group. Moreover, a docked pose of compounds 10 and 12 was obtained bound to caspase-3 active site using Molecular Operating Environment module. This study demonstrated that benzimidazole derivatives 10 and 12 provoke cytotoxicity and induced apoptosis in liver cancer cells HepG2.

  1. Synthesis of β-carboline-benzimidazole conjugates using lanthanum nitrate as a catalyst and their biological evaluation. (United States)

    Kamal, Ahmed; Rao, M P Narasimha; Swapna, P; Srinivasulu, Vunnam; Bagul, Chandrakant; Shaik, Anver Basha; Mullagiri, Kishore; Kovvuri, Jeshma; Reddy, Vangala Santhosh; Vidyasagar, K; Nagesh, Narayana


    A series of β-carboline-benzimidazole conjugates bearing a substituted benzimidazole and an aryl ring at C3 and C1 respectively were designed and synthesized. The key step of their preparation was determined to involve condensation of substituted o-phenylenediamines with 1-(substituted phenyl)-9H-pyrido[3,4-b]indole-3-carbaldehyde using La(NO3)3·6H2O as a catalyst and their cytotoxic potential was evaluated. Conjugates 5a, 5d, 5h and 5r showed enhanced cytotoxic activity (GI50 values range from 0.3 to 7.1 μM in most of the human cancer cell lines) in comparison to some of the previously reported β-carboline derivatives. To substantiate the cytotoxic activity and to understand the nature of interaction of these conjugates with DNA, spectroscopy, DNA photocleavage and DNA topoisomerase I inhibition (topo-I) studies were performed. These conjugates (5a, 5d and 5r) effectively cleave pBR322 plasmid DNA in the presence of UV light. In addition, the effect of these conjugates on DNA Topo I inhibition was studied. The mode of binding of these new conjugates with DNA was also examined by using both biophysical as well as molecular docking studies, which supported their multiple modes of interaction with DNA. Moreover, an in silico study of these β-carboline-benzimidazole conjugates reveals that they possess drug-like properties.

  2. cRGD-Modified Benzimidazole-based pH-Responsive Nanoparticles for Enhanced Tumor Targeted Doxorubicin Delivery. (United States)

    Liu, Jinjian; Liu, Qian; Yang, Cuihong; Sun, Yu; Zhang, Yumin; Huang, Pingsheng; Zhou, Junhui; Liu, Qiang; Chu, Liping; Huang, Fan; Deng, Liandong; Dong, Anjie; Liu, Jianfeng


    Finding a smart cancer drug delivery carrier with long blood circulation, enhanced cancer targeting, and quick drug release in tumors is critical for efficient cancer chemotherapy. Herein, we design a cRGD-polycarboxybetaine methacrylate-b-polybenzimidazole methacrylate (cRGD-PCB-b-PBBMZ) copolymer to self-assemble into smart drug-loaded nanoparticles (cRGD-PCM NPs) which can target αvβ3 integrin overexpressed cancer tissue by cRGD peptide unit and release drug quickly in cancer cells by protonation of benzimidazole groups. The outer PCB layer can resist protein adhesion, and there are only about 10% of proteins in mouse serum adhered to the surface of PCM NPs. With the pKa value of 5.08 of the benzimidazole units, DOX can be released from NPs in pH 5.0 PBS. cRGD-PCM NPs can bring more DOX into HepG2 cells than nontargeting PCM NPs, and there has high DOX release rate in HepG2 cells because of the protonation of benzimidazole groups in endosome and lysosome. MTT assay verifies that higher cellular uptake of DOX causes higher cytotoxicity. Furthermore, the results of ex vivo imaging studies confirm that cRGD-PCM/DOX NPs can successfully deliver DOX into tumor tissue from the injection site. Therefore, the multifunctional cRGD-PCM NPs show great potential as novel nanocarriers for targeting cancer chemotherapy.

  3. Polymer supported synthesis of novel benzoxazole linked benzimidazoles under microwave conditions: in vitro evaluation of VEGFR-3 kinase inhibition activity. (United States)

    Chanda, Kaushik; Maiti, Barnali; Yellol, Gorakh S; Chien, Ming-Hsien; Kuo, Min-Liang; Sun, Chung-Ming


    An efficient soluble polymer-supported method has been developed for the parallel synthesis of substituted benzimidazole linked benzoxazoles using focused microwave irradiation. The key step involves the amidation of 4-hydroxy-3-nitrobenzoic acid with polymer-immobilized o-phenylenediamine. Application of mild acidic conditions promoted the ring closure to furnish the benzimidazole ring. After hydrogenation of the nitro-group to amine, the resulted polymer conjugates underwent efficient ring closure with various alkyl, aryl and heteroaryl isothiocyanates to generate the polymer-bound benzimidazolyl benzoxazoles. The polymer-bound compounds were finally cleaved from the support to furnish benzimidazole linked benzoxazole derivatives. The efficacy of the resultant angular bis-heterocyclic library was studied against vascular endothelial growth factor receptor (VEGFR-3). The preliminary screening of these novel compounds exhibits moderate to high inhibition (IC(50) = 0.56-1.42 μM). This protocol provides an easy access to novel angular bis-heterocycles which have potential for the discovery of novel leads for targeted cancer therapeutics.

  4. Palladium(II) and platinum(II) complexes containing benzimidazole ligands: Molecular structures, vibrational frequencies and cytotoxicity (United States)

    Abdel Ghani, Nour T.; Mansour, Ahmed M.


    (1H-benzimidazol-2-ylmethyl)-(4-methoxyl-phenyl)-amine (L 1), (1H-benzimidazol-2-ylmethyl)-(4-methyl-phenyl)-amine (L 2) and their Pd(II) and Pt(II) complexes have been synthesized as potential anticancer compounds and their structures were elucidated using a variety of physico-chemical techniques. Theoretical calculations invoking geometry optimization, vibrational assignments, 1H NMR, charge distribution and molecular orbital description HOMO and LUMO were done using density functional theory. Natural bond orbital analysis (NBO) method was performed to provide details about the type of hybridization and the nature of bonding in the studied complexes. Strong coordination bonds (LP(1)N11 → σ *(M sbnd Cl22)) and (LP(1)N21 → σ *(M sbnd Cl23)) (M = Pd or Pt) result from donation of electron density from a lone pair orbital on the nitrogen atoms to the acceptor metal molecular orbitals. The experimental results and the calculated molecular parameters revealed square-planar geometries around the metallic centre through the pyridine-type nitrogen of the benzimidazole ring and secondary amino group and two chlorine atoms. The activation thermodynamic parameters were calculated using non-isothermal methods. The synthesized ligands, in comparison to their metal complexes were screened for their antibacterial activity. In addition, the studied complexes showed activity against three cell lines of different origin, breast cancer (MCF-7), Colon Carcinoma (HCT) and human heptacellular carcinoma (Hep-G2) comparable to cis-platin.

  5. Alternative energy production pathways in Taenia crassiceps cysticerci in vitro exposed to a benzimidazole derivative (RCB20). (United States)

    Fraga, Carolina Miguel; Da Costa, Tatiane Luiza; De Castro, Ana Maria; Reynoso-Ducoing, Olivia; Ambrosio, Javier; Hernández-Campos, Alicia; Castillo, Rafael; Vinaud, Marina Clare


    Biochemical studies of benzimidazole derivatives are important to determine their mode of action and activity against parasites. The lack of antihelminthic alternatives to treat parasitic infections and albendazole resistance cases make the search for new antiparasitary drugs of utmost importance. The 6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole (RCB20) is a benzimidazole derivative with promising effect. This study evaluated the effect of different concentrations of RCB20 in the alternative energetic pathway of in vitro Taenia crassiceps cysticerci. The parasites were in vitro exposed to 6.5 and 13 µM of RCB20 and albendazole sulfoxide (ABZSO). The quantification of acetate, acetoacetate, β-hydroxybutyrate, fumarate and propionate was performed by high-performance liquid chromatography. The quantification of urea, creatinine and total proteins was performed by spectrophotometry. The increase in β-hydroxybutyrate reflects the enhancement of the fatty acid oxidation in the treated groups. Volatile fatty acids secretion, acetate and propionate, was increased in the treated groups. The secretion mechanisms of the treated parasites were impaired due to organic acids increased concentrations in the cysticerci. It is possible to conclude that the metabolic effect on alternative energetic pathways is slightly increased in the parasites treated with RCB20 than the ones treated with ABZSO.

  6. Activity of benzimidazoles against Dientamoeba fragilis (Trichomonadida, Monocercomonadidae in vitro and correlation of beta-tubulin sequences as an indicator of resistance

    Directory of Open Access Journals (Sweden)

    Stark Damien


    Full Text Available Recently, Dientamoeba fragilis has emerged as a significant and common enteropathogen. The majority of patients with dientamoebiasis present with gastrointestinal complaints and chronic symptoms are common. Numerous studies have successfully demonstrated parasite clearance, coupled with complete resolution of clinical symptoms following treatment with various antiparasitic compounds. Despite this, there is very little in vitro susceptibility data available for the organism. Benzimidazoles are a class of antiparasitic drugs that are commonly used for the treatment of protozoan and helminthic infections. Susceptibility testing was undertaken on four D. fragilis clinical isolates against the following benzimidazoles: albendazole, flubendazole, mebendazole, nocodazole, triclabendazole and thiabendazole. The activities of the antiprotozoal compounds at concentrations ranging from 2 μg/mL to 500 μg/mL were determined via cell counts of D. fragilis grown in xenic culture. All tested drugs showed no efficacy. The beta-tubulin transcript was sequenced from two of the D. fragilis isolates and amino acid sequences predicted a susceptibility to benzimidazoles. This is the first study to report susceptibility profiles for benzimidazoles against D. fragilis, all of which were not active against the organism. This study also found that beta-tubulin sequences cannot be used as a reliable marker for resistance of benzimidazoles in D. fragilis.

  7. Benzimidazole inhibitors of the protein kinase CHK2: Clarification of the binding mode by flexible side chain docking and protein–ligand crystallography (United States)

    Matijssen, Cornelis; Silva-Santisteban, M. Cris; Westwood, Isaac M.; Siddique, Samerene; Choi, Vanessa; Sheldrake, Peter; van Montfort, Rob L.M.; Blagg, Julian


    Two closely related binding modes have previously been proposed for the ATP-competitive benzimidazole class of checkpoint kinase 2 (CHK2) inhibitors; however, neither binding mode is entirely consistent with the reported SAR. Unconstrained rigid docking of benzimidazole ligands into representative CHK2 protein crystal structures reveals an alternative binding mode involving a water-mediated interaction with the hinge region; docking which incorporates protein side chain flexibility for selected residues in the ATP binding site resulted in a refinement of the water-mediated hinge binding mode that is consistent with observed SAR. The flexible docking results are in good agreement with the crystal structures of four exemplar benzimidazole ligands bound to CHK2 which unambiguously confirmed the binding mode of these inhibitors, including the water-mediated interaction with the hinge region, and which is significantly different from binding modes previously postulated in the literature. PMID:23058106

  8. Synthesis of benzimidazole-grafted graphene oxide/multi-walled carbon nanotubes composite for supercapacitance application

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Rajesh Kr., E-mail: [Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, 637371 Singapore (Singapore); Xingjue, Wang [Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, 637371 Singapore (Singapore); Kumar, Vinod [Department of Zoology, Banaras Hindu University, Varanasi (India); Srivastava, Anchal [Department of Physics, Banaras Hindu University, Varanasi (India); Singh, Vidya Nand [CSIR-National Physical Laboratory, New Delhi (India)


    Highlights: • We are reporting supercapacitance performance of BI-GO/MWCNTs composite. • The specific capacitance of BI-GO/MWCNTs is 275 and 460 F/g at 200 and 5 mV/s scan rate. • This composite has shown 224 F/g capacitance after 1300 cycles at 200 mV/s scan rate. - Abstract: We are reporting the fabrication, characterizations and supercapacitance performance of benzimidazole-grafted graphene oxide/multi-walled carbon nanotubes (BI-GO/MWCNTs) composite. The synthesis of BI-GO materials involves cyclization reaction of carboxylic groups on GO among the hydroxyl and amino groups on o-phenylenediamine. The BI-GO/MWCNTs composite has been fabricated via in situ reduction of BI-GO using hydrazine in presence of MWCNTs. Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), Raman spectroscopy, X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) have been used to characterize its surface and elemental composition. The uniform dispersion of MWCNTs with BI-GO helps to improve the charge transfer reaction during electrochemical process. The specific capacitance of BI-GO/MWCNTs composite is 275 and 460 F/g at 200 and 5 mV/s scan rate in 1 mol/L aqueous solution of H{sub 2}SO{sub 4}. This BI-GO/MWCNTs composite has shown 224 F/g capacitance after 1300 cycles at 200 mV/s scan rate, which represents its good electrochemical stability.

  9. Porous poly(benzimidazole) membrane for all vanadium redox flow battery (United States)

    Luo, Tao; David, Oana; Gendel, Youri; Wessling, Matthias


    Porous poly(benzimidazole) (PBI) membranes of low vanadium ions permeability are described for an all vanadium redox flow battery (VRFB). The PBI membrane was prepared by a water vapour induced phase inversion process of a PBI polymer solution. The membrane has a symmetrical cross-sectional morphology. A low water permeability of 16.5 L (m2 h bar)-1 indicates the high hydraulic resistance stemming from a closed cell morphology with nanoporous characteristics. The PBI membrane doped with 2.5 M H2SO4 shows a proton conductivity of 16.6 mS cm-1 and VO2+ permeability as low as 4.5 × 10-8 cm2 min-1. The stability test of dense PBI membrane in VO2+ solution indicates good chemical stability. An all vanadium redox flow battery (VRFB) operated with the porous PBI membrane shows 98% coulombic efficiency and more than 10% higher energy efficiency compared to VRFB operated with Nafion 112 at applied current densities of 20-40 mA cm-2. High in situ stability of the porous PBI membrane was confirmed by about 50 cycles of continuous charge and discharge operation of the battery.

  10. Immunohistochemical expression of budding uninhibited by benzimidazole related 1 in leukoplakia and oral squamous cell carcinoma

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    Taneeru Sravya


    Full Text Available Background: Budding uninhibited by benzimidazole related 1 (BUBR1 is an important protein in the mitotic spindle assembly checkpoint. Alterations in expression of BUBR1 have been reported in many premalignant and malignant lesions. Aim: To compare the expression of BUBR1 with respect to the normal mucosa and degree of dysplasia in oral leukoplakia (OL and also with respect to different histopathological grades of oral squamous cell carcinoma (OSCC. Materials and Methods: Neutral buffered formalin-fixed and paraffin-embedded biopsy specimens 30 each of normal, OL and OSCC tissue were included in this study. The expression of BUBR1 was detected using immunohistochemistry (IHC. The scores obtained were subjected to ANOVA test. Results: Significant correlation was found in immunostaining between normal, dysplasia and OSCC groups with a P value of 0.00001. The expression of BUBR1 was significant when compared with different degrees of dysplasia and in different histopathological grades of OSCC with a P value of 0.00001. Conclusion: Higher IHC scores were obtained with increased histopathological grades of OL and OSCC suggesting its role as a prognostic indicator.

  11. Synthesis and anti-fungicidal activity of some transition metal complexes with benzimidazole dithiocarbamate ligand (United States)

    Mohamed, Gehad G.; Ibrahim, Nasser A.; Attia, Hanaa A. E.


    Seven transition metal complexes of benzimidazole ligand (HL) are reported and characterized based on elemental analyses, IR, solid reflectance, magnetic moment, molar conductance and thermal analyses (TGA and DTA). From the obtained data, the complexes were proposed to have the general formulae [MX 2(HL)(H 2O)]· yH 2O, where M = Mn(II), Co(II), Ni(II), Cu(II), Zn(II), Cr(III); X = Cl -, SO 42- and y = 0-4. The molar conductance data revealed that all the metal chelates were non-electrolytes. From the magnetic and solid reflectance spectra, it was found that the geometrical structure of these complexes is octahedral. The thermal behaviour of these chelates showed that the hydrated complexes loss water molecules of hydration in the first step followed immediately by decomposition of the anions and ligand molecules in the subsequent steps. Fungicidal activity of the prepared complexes and free ligand was evaluated against three soil borne fungi. Data obtained showed the higher biological activity of the prepared complexes than the parent Schiff base ligand. Formulation of the most potent complex was carried out in the form of 25% WP. Fungicidal activity of the new formulation was evaluated and compared with the standard fungicide Pencycuron (Monceren 25% WP). In most cases, the new formulation possessed higher fungicidal activity than the standard fungicide under the laboratory conditions.

  12. Dye-sensitized photodegradation of the fungicide carbendazim and related benzimidazoles. (United States)

    Escalada, Juan P; Pajares, Adriana; Gianotti, José; Massad, Walter A; Bertolotti, Sonia; Amat-Guerri, Francisco; García, Norman A


    The present work studies the visible-light-promoted photodegradation of the colorless fungicide carbendazim (methyl 2-benzimidazolecarbamate) and several 2-substituted benzimidazoles (SBZ's), in water or water-methanol solution, in the presence of air and, as a photosensitizer, the synthetic xanthene dye Rose Bengal (RB) or the natural pigment riboflavin (Rf). The results indicate that the degradation of each particular SBZ depends on its chemical structure and on the sensitizer employed. In the presence of RB, the degradation always operates via a singlet molecular oxygen (O(2)((1)Delta(g)))-mediated mechanism, through a highly efficient process, as deduced from the comparison of the rate constants for physical and chemical quenching of O(2)((1)Delta(g)). In the presence of Rf, the visible-light irradiation of any of the studied SBZ's produces a series of competitive processes that depend on the relative concentrations of Rf and SBZ. These processes include the quenching of excited singlet and triplet Rf states by the SBZ and the generation of both O(2)((1)Delta(g)) and superoxide radical anion (O(2)(-)), the latter generated by electron transfer from excited Rf species to the dissolved oxygen. The overall result is the photodegradation of the SBZ and the photoprotection of the sensitizer.

  13. Benzimidazole bearing oxadiazole and triazolo-thiadiazoles nucleus: design and synthesis as anticancer agents. (United States)

    Husain, Asif; Rashid, Mohd; Mishra, Ravinesh; Parveen, Shama; Shin, Dong-Soo; Kumar, Deepak


    Two new series of benzimidazole bearing oxadiazole[1-(1H-benzo[d]imidazol-2-yl)-3-(5-substituted-1,3,4-oxadiazol-2-yl)propan-1-ones (4a-l)] and triazolo-thiadiazoles[1-(1H-benzo[d]imidazol-2-yl)-3-(6-(substituted)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl)propan-1-one (7a-e)] have been synthesized successfully from 4-(1H-benzo[d]imidazol-2-yl)-4-oxobutanehydrazide (3) with an aim to produce promising anticancer agents. In vitro anticancer activities of synthesized compounds were screened at the National Cancer Institute (NCI), USA, according to their applied protocol against full NCI 60 human cell lines panel; results showed good to remarkable anticancer activity. Among them, compound (4j, NCS: 761980) exhibited significant growth inhibition and further screened at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 μM) with GI(50) values ranging from 0.49 to 48.0 μM and found superior for the non-small cell lung cancer cell lines like HOP-92 (GI(50) 0.49, TGI 19.9,LC(50) >100 and Log(10)GI(50) -6.30, Log(10)TGI -4.70, Log(10)LC(50) >-4.00).

  14. Benzimidazole clubbed with triazolo-thiadiazoles and triazolo-thiadiazines: new anticancer agents. (United States)

    Husain, Asif; Rashid, Mohd; Shaharyar, M; Siddiqui, Anees A; Mishra, Ravinesh


    Two series of Benzimidazole clubbed with triazolo-thiadiazoles (5a-q, 5r, 5s and 5x-a(1)) and triazolo-thiadiazines (5t-w) were synthesized with an aim to produce promising anticancer agents. In vitro anticancer activities of synthesized compounds were investigated at the National Cancer Institute (NCI) against NCI 60 cell line panel; results showed good to remarkable broad-spectrum anticancer activity. Among them, the compound 5h (NCS: 760452, 1-(1H-benzo [d] imidazol-2-yl)-3-(6-(2,4-dichlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl) propan-1-one) exhibited significant growth inhibition with GI50 values ranging from 0.20 to 2.58 μM and found superior selectivity for the leukemia cell lines and further screened at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 μM). The 5h may possibly be used as lead compound for developing new anticancer agents.

  15. Benzimidazoles diminish ERE transcriptional activity and cell growth in breast cancer cells. (United States)

    Payton-Stewart, Florastina; Tilghman, Syreeta L; Williams, LaKeisha G; Winfield, Leyte L


    Estrogen receptors (ERα and ERβ) are members of the nuclear receptor superfamily. They regulate the transcription of estrogen-responsive genes and mediate numerous estrogen related diseases (i.e., fertility, osteoporosis, cancer, etc.). As such, ERs are potentially useful targets for developing therapies and diagnostic tools for hormonally responsive human breast cancers. In this work, two benzimidazole-based sulfonamides originally designed to reduce proliferation in prostate cancer, have been evaluated for their ability to modulate growth in estrogen dependent and independent cell lines (MCF-7 and MDA-MB 231) using cell viability assays. The molecules reduced growth in MCF-7 cells, but differed in their impact on the growth of MDA-MB 231 cells. Although both molecules reduced estrogen response element (ERE) transcriptional activity in a dose dependent manner, the contrasting activity in the MDA-MB-231 cells seems to suggest that the molecules may act through alternate ER-mediated pathways. Further, the methyl analog showed modest selectivity for the ERβ receptor in an ER gene expression array panel, while the naphthyl analog did not significantly alter gene expression. The molecules were docked in the ligand binding domains of the ERα-antagonist and ERβ-agonist crystal structures to evaluate the potential of the molecules to interact with the receptors. The computational analysis complimented the results obtained in the assay of transcriptional activity and gene expression suggesting that the molecules upregulate ERβ activity while down regulating that of ERα.

  16. Competitive binding of a benzimidazole to the histone-binding pocket of the Pygo PHD finger. (United States)

    Miller, Thomas C R; Rutherford, Trevor J; Birchall, Kristian; Chugh, Jasveen; Fiedler, Marc; Bienz, Mariann


    The Pygo-BCL9 complex is a chromatin reader, facilitating β-catenin-mediated oncogenesis, and is thus emerging as a potential therapeutic target for cancer. Its function relies on two ligand-binding surfaces of Pygo's PHD finger that anchor the histone H3 tail methylated at lysine 4 (H3K4me) with assistance from the BCL9 HD1 domain. Here, we report the first use of fragment-based screening by NMR to identify small molecules that block protein-protein interactions by a PHD finger. This led to the discovery of a set of benzothiazoles that bind to a cleft emanating from the PHD-HD1 interface, as defined by X-ray crystallography. Furthermore, we discovered a benzimidazole that docks into the H3K4me specificity pocket and displaces the native H3K4me peptide from the PHD finger. Our study demonstrates the ligandability of the Pygo-BCL9 complex and uncovers a privileged scaffold as a template for future development of lead inhibitors of oncogenesis.

  17. Selective ALDH3A1 inhibition by benzimidazole analogues increase mafosfamide sensitivity in cancer cells. (United States)

    Parajuli, Bibek; Fishel, Melissa L; Hurley, Thomas D


    Aldehyde dehydrogenase enzymes irreversibly oxidize aldehydes generated from metabolism of amino acids, fatty acids, food, smoke, additives, and xenobiotic drugs. Cyclophosphamide is one such xenobiotic used in cancer therapies. Upon activation, cyclophosphamide forms an intermediate, aldophosphamide, which can be detoxified to carboxyphosphamide by aldehyde dehydrogenases (ALDH), especially ALDH1A1 and ALDH3A1. Consequently, selective inhibition of ALDH3A1 could increase chemosensitivity toward cyclophosphamide in ALDH3A1 expressing tumors. Here, we report detailed kinetics and structural characterization of a highly selective submicromolar inhibitor of ALDH3A1, 1-[(4-fluorophenyl)sulfonyl]-2-methyl-1H-benzimidazole (CB7, IC50 of 0.2 μM). CB7 does not inhibit ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, or ALDH2 activity. Structural, kinetics, and mutagenesis studies show that CB7 binds to the aldehyde binding pocket of ALDH3A1. ALDH3A1-expressing lung adenocarcinoma and glioblastoma cell lines are sensitized toward mafosfamide (MF) treatment in the presence analogues of CB7, whereas primary lung fibroblasts lacking ALDH3A1 expression, are not.

  18. Purine-benzimidazole hybrids: synthesis, single crystal determination and in vitro evaluation of antitumor activities. (United States)

    Sharma, Alka; Luxami, Vijay; Paul, Kamaldeep


    In an effort to identify novel compounds for the treatment of cancer, a diverse array of potential bioactive hybrid, purine-benzimidazole was synthesized in good yields through nucleophilic substitution at C6 position of purine ring with versatile cyclic amines at C2 position. The structures of newly prepared compounds were confirmed by IR, (1)H, (13)C NMR, mass spectroscopy and, in case of 19, by single crystal X-ray diffraction analysis. The newly synthesized compounds were evaluated against 60 human tumour cell lines at one dose concentration level. Compound 6 exhibited significant growth inhibition and was evaluated as 60 cell panel at five dose concentration levels. Compound 6 proved to be 1.25 fold more active than the positive control 5-FU, with GI50 value of 18.12 μM (MG-MID). Interaction of the compounds with Aurora-A enzyme involved in the process of propagation of cancer, has also been investigated. Compound 6 showed selectivity towards Aurora-A kinase inhibition with IC50 value of 0.0l μM. Molecular docking studies in the active binding site provided theoretical support for the experimental biological data acquired.

  19. New benzimidazoles and their antitumor effects with Aurora A kinase and KSP inhibitory activities. (United States)

    Abd El-All, Amira S; Magd-El-Din, Asmaa A; Ragab, Fatma A F; ElHefnawi, Mahmoud; Abdalla, Mohamed M; Galal, Shadia A; El-Rashedy, Ahmed A


    A newly synthesized series of anticancer compounds comprising thiazolo[3,2-a]pyrimidine derivatives 6a-q bearing a benzimidazole moiety was produced via a one-pot reaction of N-(4-(1H-benzo[d]imidazol-2-yl)phenyl)-2-cyanoacetamide 5 with 2-aminothiazole and an appropriate aromatic aldehyde. Compound 7 was obtained via the reaction of 4-(1H-benzo[d]imidazol-2yl)benzenamide 1 with carbon disulphide and methyl iodide in the presence of concentrated aqueous solution of NaOH, then treated with o-phenylenediamine to give N-(4-1H-benzo[d]imidazol-2-yl)phenyl)-1H-benzo[d]imidazol-2-amine 8. The structures of the newly synthesized compounds were confirmed by analytical and spectroscopic measurements (IR, MS, and (1) H NMR). The synthesized products were screened and studied for their in vitro antitumor activity against three human cancer cell lines (namely colorectal cancer cell line HCT116, human liver cancer cell line HepG2, and human ovarian cancer cell line A2780) and their Aurora A kinase and KSP inhibitory activities. All newly synthesized compounds revealed marked results comparable with the standard drug CK0106023. The compounds 6e and 6k of the thiazolopyrimidine derivatives were the most active compounds when tested against the three cell lines in comparison with the standard drug CK0106023, and showed potent dual KSP and Aurora A kinase inhibition.

  20. Synthesis and Biological Evaluation of 2-Aminobenzothiazole and Benzimidazole Analogs Based on the Clathrodin Structure. (United States)

    Montalvão, Sofia; Leino, Teppo O; Kiuru, Paula S; Lillsunde, Katja-Emilia; Yli-Kauhaluoma, Jari; Tammela, Päivi


    A series of 2-aminobenzothiazole and benzimidazole analogs based on the clathrodin scaffold was synthesized and investigated for their antimicrobial and antiproliferative activities as well as for their effects in hepatitis C virus (HCV) replicon model. Compound 7, derived from 2-aminobenzothiazole, exhibited moderate antimicrobial activity only against the Gram-positive bacterium, Enterococcus faecalis. In the antiviral assay, compounds 4d and 7 were found to suppress the HCV replicon by >70%, but also to exhibit cytotoxicity against the host cells (35 and 44%, respectively). Compounds 4a and 7 demonstrated good activity in the antiproliferative assays on the human melanoma cell line A-375. To assess the selectivity of the effects between cancerous and noncancerous cells, a mouse fibroblast cell line was used. The IC50 values for compound 7 against the melanoma cell line A-375 and the fibroblast cell line BALB/c 3T3 were 16 and 71 µM, respectively, yielding fourfold selectivity toward the cancer cell line. These results suggest that compound 7 should be studied further in order to fully explore its potential for drug development.

  1. Resistance to benzimidazoles and levamisole in nematode parasites of sheep in Nyandarua district of Kenya

    DEFF Research Database (Denmark)

    Maingi, N.; Bjørn, H.; Gichohi, V.M.;


    The occurrence of anthelmintic resistance on 25 sheep farms in the Nyandarua District of Kenya was investigated, using the faecal egg count reduction test (FECRT), the egg hatch assay (EHA) and a larval development assay (LDA). In the FECRT, resistance to both benzimidazoles (BZs) and levamisole...... (LEV) was detected on four farms, resistance to LEV only on three farms and to BZs, only on two farms. Haemonchus contortus was the predominant nematode species in both pre-treatment and post-treatment faecal cultures. Out of the six farms where BZ resistance was detected in the FECRT, only isolates...... from one farm had an LD50 value higher than 0.5 mu M thiabendazole (TBZ) (0.1 mu g TBZ/ml) in the EHA indicating resistance. Isolates from three other farms, where susceptibility to BZs was detected and four with suspected BZ resistance in the FECRT, had LD50 values higher than 0.5 mu M TBZ in the EHA...

  2. Synthesis and evaluation of novel benzimidazole derivative [Bz-Im] and its radio/biological studies. (United States)

    Tiwari, Anjani K; Mishra, Anil K; Bajpai, Aruna; Mishra, Pushpa; Singh, Sweta; Sinha, Deepa; Singh, V K


    Two different benzimidazole analogues act as multimodal agent, first one as novel non-peptidic CCK-B receptor antagonist and similarly as potent anti-fungal agent, designated as [Bz-Im]. These compounds were synthesized and characterized by spectroscopic techniques such as FT-IR, NMR, EI-MS and also evaluated for specific radiopharmaceuticals. Preliminary radiolabeling results with (99m)Tc and biological evaluation studies showed promising results for further evaluation in vivo. The efficiency of labeling was more than 97% and complex was stable for about 12h at 30 degrees C in the presence of serum. Both ligands showed binding to most of the organs, known to express CCK receptors in biodistribution studies. Cholecystokinin (CCK(1) andCCK(2)) receptor binding affinities of these analogues are, IC(50), 0.942+/-0.107 for compound C and 0.665+/-0.211 for compound D in rat pancreatic acini. The anti-fungal activity has shown inhibitory activity against Aspergillus flavus and Aspergillus niger. These studies have provided a new template for further development of non-peptidic ligands for diagnostic and therapeutic purposes of diseases related with CCK receptors as well as anti-microbes.

  3. Potent inhibition of protein tyrosine phosphatases by copper complexes with multi-benzimidazole derivatives. (United States)

    Li, Ying; Lu, Liping; Zhu, Miaoli; Wang, Qingming; Yuan, Caixia; Xing, Shu; Fu, Xueqi; Mei, Yuhua


    A series of copper complexes with multi-benzimidazole derivatives, including mono- and di-nuclear, were synthesized and characterized by Fourier transform IR spectroscopy, UV-Vis spectroscopy, elemental analysis, electrospray ionization mass spectrometry. The speciation of Cu/NTB in aqueous solution was investigated by potentiometric pH titrations. Their inhibitory effects against human protein tyrosine phosphatase 1B (PTP1B), T-cell protein tyrosine phosphatase (TCPTP), megakaryocyte protein tyrosine phosphatase 2 (PTP-MEG2), srchomology phosphatase 1 (SHP-1) and srchomology phosphatase 2 (SHP-2) were evaluated in vitro. The five copper complexes exhibit potent inhibition against PTP1B, TCPTP and PTP-MEG2 with almost same inhibitory effects with IC(50) at submicro molar level and about tenfold weaker inhibition versus SHP-1, but almost no inhibition against SHP-2. Kinetic analysis indicates that they are reversible competitive inhibitors of PTP1B. Fluorescence study on the interaction between PTP1B and complex 2 or 4 suggests that the complexes bind to PTP1B with the formation of a 1:1 complex. The binding constant are about 1.14 × 10(6) and 1.87 × 10(6) M(-1) at 310 K for 2 and 4, respectively.

  4. Crystal Structure and Electronic Structure of a Luminescent Compound 2-(2-Pyridyl) Benzimidazole

    Institute of Scientific and Technical Information of China (English)

    岳淑美; 苏忠民; 马建方; 廖奕; 阚玉和; 张恒君


    The crystal structure of 2-(2-pyridyl) benzimidazole was determined by singlecrystal X-ray diffraction at 193(2) K. It crystallizes in orthorhombic system, space group Pbca with unit cell constants a = 10.6204(7), b = 10.1407(4), c = 18.6327(8) A, Z= 8, V= 2006.7(2) A3, Dc. =1.292 g/cm3, F(000) = 816 andμ(MoKα) = 0.081 mm-1. The structure was refined to R = 0.0317 and wR = 0.0454 for 795 observed reflections with Ⅰ> 2σ(Ⅰ). In the solid state, it has an emission maximum at 369 nm, while in solution (DMSO), the maximum excitation is at 372 nm. Quantum chemistry calculation was performed by the method of density functional theory. Theoretical results show that atom N is the reactive site when coordinating with a metal, and the electronic structure of the title compound presents excellent carrier transport properties.

  5. Synthesis and Crystal Structure of catena-Poly[bis-(benzimidazole)cobalt(Ⅱ) μ- Phthalato

    Institute of Scientific and Technical Information of China (English)

    XUE Yu-Hong; ZHANG Li; XU Duan-Jun


    The title polymeric complex [Co(C8H4O4)(C7H6N2)2]n has been prepared and its crystal structure was determined by X-ray diffraction method. The crystal belongs to monoclinic,space group C2/c with a = 7.7865(12), b = 20.4215(18), c = 13.4880(14) (A),β = 103.298(2)°, V = 2087.3(4) (A)3, Mr = 459.32, Z = 4, Dc= 1.462 g/cm3,μ = 0.859 mm-1, F(000) = 940, R = 0.0636 and wR = 0.1639 for 1278 observed reflections (I > 2σ(Ⅰ)). The complex assumes a distorted tetrahedral coordination geometry, formed by two phthalate anions and two benzimidazoles (bzim). The phthalate anions bridge the neighboring Co(Ⅱ) atoms to form the polymeric chains. The centroid distance of 3.471(3) (A) between the parallel bzim rings of adjacent polymeric chains suggests the existence of π-π stacking.

  6. Synthesis and Photovoltaic Properties of Polymers Based on Cyclopentadithiophene and Benzimidazole Units

    Energy Technology Data Exchange (ETDEWEB)

    Song, Su Hee; Park, Sei Jung; Shim, Joo Young; Kim, Il; Suh, Hong Suk [Pusan National University, Busan (Korea, Republic of); Kwon, Soon Cheol; Lee, Kwang Hee [Gwangju Institute of Science and Technology, Gwangju (Korea, Republic of); Jin, Young Eup; Park, Sung Heum [Pukyong National University, Busan (Korea, Republic of)


    The new semiconducting copolymers with 4,4-dialkyl-4H-cyclopenta[2,1-b:3,4-b']dithiophene and 2,2-dimethyl- 2H-benzimidazole units were synthesized. The fused aromatic rings, such as cyclopentadithiophene (CPDT) unit, can make the polymer backbone more rigid and coplanar, which induces long conjugation length, narrow band gap, and strong intermolecular {pi}-{pi} interaction. The stacking ability was controlled through attaching of linear or branched alkyl side chains. The spectra of PEHCPDTMBI and PHCPDTMBI in the solid films show absorption bands with maximum peaks at 401, 759 and 407, 768 nm, and the absorption onsets at 925 and 954 nm, corresponding to band gaps of 1.34 and 1.30 eV, respectively. The devices comprising PHCPDTMBI with TiO{sub X} showed a V{sub OC} of 0.39 V, a J{sub SC} of 1.14 mA/cm{sup 2}, and a FF of 0.34, giving a power conversion efficiency of 0.15%. The PHCPDTMBI with linear alkyl chain on CPDT shows good solubility in organic solvent with higher PCE value than that of PEHCPDTMBI

  7. Self-assembled 1-octadecyl-1H-benzimidazole film on copper surface for corrosion protection

    Indian Academy of Sciences (India)

    B V Appa Rao; M Marsihma Reddy


    Films of 1-octadecyl-1H-benzimidazole (OBI) have been formed on copper surface by selfassembly method. Optimum conditions viz. the solvent, concentration of OBI, immersion period and temperature for the formation of a protective film on copper have been established using impedance studies. The OBI film has been characterized by X-ray photoelectron spectroscopy, reflection absorption Fourier transform infrared (FTIR) spectroscopy, contact angle measurements and atomic force microscopy. Efficiency of the OBI film to protect copper from corrosion has been investigated in aq. HCl solution using electrochemical impedance spectroscopy, potentiodynamic polarization method, cyclic voltammetry, scanning electron microscopy and gravimetry. Results of these studies inferred that the OBI film has an inhibition efficiency in the range of 97-99% under different conditions. Polarization studies inferred that the OBI film functions as a cathodic inhibitor. Cyclic voltammetric studies showed that the film is stable even after 15 cycles, when the copper electrode is polarized to an anodic potential of 0.35V vs. Ag/AgCl electrode.

  8. In vitro detection of benzimidazole resistance in Haemonchus contortus: egg hatch test versus larval development test. (United States)

    Várady, M; Cudeková, P; Corba, J


    The present study was designed to compare the egg hatch test (EHT) and the larval development test (LDT) as in vitro tools for detection of benzimidazole (BZ) resistance in Haemonchus contortus, a nematode parasite of small ruminants. Comparisons were made during a course of infection and changes in both EHT and LDT were monitored to measure the correlation between resistance and susceptibility in different parasite stages (eggs and larvae). In addition, mixed doses of known numbers of susceptible and BZ-resistant H. contortus eggs were used to assess the sensitivity of LDT for the detection of low levels of resistance. The degree of resistance for each test was expressed as resistance factor (RF). The LDT showed a greater ability to distinguish between four susceptible and four resistant isolates of H. contortus with higher resistance factors compared to the EHT. For the EHT the RF by using ED(50) criterion ranged from 3.2 to 13.3 and from 7.4 to 25.2 by using LC(99). For LDT the resistant isolates were 4.3-63.1 times more tolerant than the susceptible isolates using the ED(50) criterion and 91.1-1411.0 times more tolerant using the LC(99) criterion. The LDT was also able to clearly indicate the presence of low level (4%) of resistant larvae amongst a susceptible background population.

  9. Synthesis and Structure of L-Aspartato-nickel(II) Complex with Benzimidazole

    Institute of Scientific and Technical Information of China (English)

    张骊; 戴志远


    The title complex Ni(C4H5NO4)(C7H6N2)3·1.75(H2O)(C25H26.5N7NiO5.75,Mr=575.74) has been prepared and its crystal structure was determined by X-ray diffraction method.The crystal of this chiral complex belongs to monoclinic,space group P21 with a=13.208(1),b=10.741(1),c=19.398(1)A,β=104.39(1)°,V=2665.8(4)A3,Z=4,Dc=1.435 g/cm3,μ(MoKα)=0.780 mm-1 and F(000)=1198.The final R=0.0504 and wR=0.1267 for 9159 observed reflections (I>2σ(I)),and R=0.065 and wR=0.1299 for 11006 independent reflections.The complex assumes a distorted octa-hedral coordinate geometry formed by one aspartate dianion and three benzimidazole ligands.The aspartate chelates to the Ni atom as a tridentate ligand.The lattice water molecules are hydrogen-bonded to the Ni complex molecule.

  10. Evaluation of Benzimidazole Resistance in Haemonchus Contortus Using Comparative PCR-RFLP Methods

    Directory of Open Access Journals (Sweden)

    S Bokaie


    Full Text Available Background: In order to deworm the ruminants especially of sheep in Iran, consumption of benzimi­dazoles has more than 2 decades history and today farmers are using imidazothiazoles, macrocyclic lactones and mostly benzimidazole compounds (BZs to treat infected farm animals. It has been demonstrated that the most common molecular mechanism leading to BZsresistance in Haemonchus contortus is a single mutation at amino acid 200 (phenylalanine to tyrosine of the isotype 1 of beta tubulin gene. According to the report of such mutations in Iranian Telador­sagia circumcincta isolates with Restriction Site Created PCR-RFLP, we decided to evaluate the frequency of such mutations in H. contortus in three different geographical areas of Iran.Methodes: A total of 102 collected adult male H. contortus were evaluated with PCR-RFLP (us­ing PSP1406I as restriction enzyme. By means of a second step to compare function of different methods and to increase sensitivity of detection mechanism, a third of samples were examined by another PCR-RFLP method (using TaaI as restriction enzyme and finally beta tubulin gene of two samples was sequenced.Results: All of samples were detected as BZss homozygote. Finally, beta tubulin gene sequenc­ing of two samples showed no point mutation at codon 200.Conclusion: It seems that BZresistance of H. contortus in Iran is not a serious problem as antici­pated before.

  11. One-pot microwave assisted synthesis under green chemistry conditions, antioxidant screening, and cytotoxicity assessments of benzimidazole Schiff bases and pyrimido[1,2-a]benzimidazol-3(4H)-ones. (United States)

    Neochoritis, Constantinos G; Zarganes-Tzitzikas, Tryfon; Tsoleridis, Constantinos A; Stephanidou-Stephanatou, Julia; Kontogiorgis, Christos A; Hadjipavlou-Litina, Dimitra J; Choli-Papadopoulou, Theodora


    The synthesis of a number of benzimidazole Schiff bases 3 and 3-oxo-pyrimido[1,2-a]benzimidazoles 4 in excellent yields by a one-step sequence from the reaction of 2-aminobenzimidazole under green chemistry conditions is described. Structural assignments of the new compounds as well as complete assignment of (1)H and (13)C NMR signals have been unambiguously achieved based on the analysis of their (1)H and (13)C NMR (1D and 2D), IR, MS and elemental analysis data. To the synthesized Schiff bases the E-configuration was assigned on the basis of comparison of experimental and calculated (DFT) (13)C NMR chemical shifts. Compounds 3 and 4 were evaluated as inhibitors of lipoxygenase (LOX) and of lipid peroxidation (LPO). All the tested derivatives showed inhibition of lipid peroxidation, whereas most of them were found to have higher activation than the reference compound trolox; The Schiff bases 3e, 3h, and 3i, and the pyrimidobenzimidazoles 4a, 4e and 4f were found to be the most potent. The most potent LOX inhibitor within the subset of Schiff bases was found compound 3i, followed by 3f, whereas compounds 4a and 4g were found the most potent of the 3-oxo-pyrimido[1,2-a]benzimidazole group. Moreover, some cytotoxicity assessments were undertaken, whereupon it was found that Schiff base 3i and pyrimidobenzimidazoles 4e and 4f did not exhibit cytotoxicity at similar concentrations resembling thus the inhibitory activity of lipid peroxidation. The most cytotoxic Schiff base and pyrimidobenzimidazole were found to be 3d and 4c, respectively.

  12. Complexes cobalt(II, zinc(II and copper(II with some newly synthesized benzimidazole derivatives and their antibacterial activity

    Directory of Open Access Journals (Sweden)



    Full Text Available The preparation and properties of some complexes of cobalt(II, zinc(II and copper(II with several newly synthesized benzimidazole derivatives (L are reported. The complexes, of the general formula [MCl2L2] (M=Co(II, Zn(II and [CuCl2L(H2O], have a tetrahedral structure. The complexes were characterized by elemental analysis, molar conductivity, magnetic susceptibility measurements, IR and absorption electronic spectra. The antibacterial activitiy of the benzimidazoles and their complexes was evaluated against Erwinia carotovora subsp. carotovora and Erwinia amylovora. The complexes were found to be more toxic than the ligands.

  13. Role of benzimidazole (Bid) in the delta-opioid agonist pseudopeptide H-Dmt-Tic-NH-CH(2)-Bid (UFP-502). (United States)

    Salvadori, Severo; Fiorini, Stella; Trapella, Claudio; Porreca, Frank; Davis, Peg; Sasaki, Yusuke; Ambo, Akihiro; Marczak, Ewa D; Lazarus, Lawrence H; Balboni, Gianfranco


    H-Dmt-Tic-NH-CH(2)-Bid (UFP-502) was the first delta-opioid agonist prepared from the Dmt-Tic pharmacophore. It showed interesting pharmacological properties, such as stimulation of mRNA BDNF expression and antidepression. To evaluate the importance of 1H-benzimidazol-2-yl (Bid) in the induction of delta-agonism, it was substituted by similar heterocycles: The substitution of NH(1) by O or S transforms the reference delta-agonist into delta-antagonists. Phenyl ring of benzimidazole is not important for delta-agonism; in fact 1H-imidazole-2-yl retains delta-agonist activity.

  14. ERK-dependent phosphorylation of HSF1 mediates chemotherapeutic resistance to benzimidazole carbamates in colorectal cancer cells. (United States)

    Wales, Christina T K; Taylor, Frederick R; Higa, Allan T; McAllister, Harvey A; Jacobs, Aaron T


    Drugs containing the benzimidazole carbamate scaffold include anthelmintic and antifungal agents, and they are now also recognized as having potential applications in the treatment of colorectal and other cancers. These agents act by binding to β-tubulin, and in doing so they disrupt microtubules, arrest cell division, and promote apoptotic cell death in malignant cells. We have evaluated several commercially available benzimidazole carbamates for cytotoxic activity in colorectal cancer cells. In addition to cytotoxicity, we also observe activation of the transcription factor, heat shock factor-1 (HSF1). HSF1 is well known to mediate a cytoprotective response that promotes tumor cell survival and drug resistance. Here, we show that biochemical inhibition with the HSF1 inhibitor KRIBB11 or siRNA-based silencing of HSF1 results in a significant enhancement of drug potency, causing an approximately two-fold decrease in IC50 values of parbendazole and nocodazole. We also define a mechanism for drug-induced HSF1 activation, which results from a phosphorylation event at Ser326 that is dependent on the activation of the extracellular regulated protein kinase-1/2 (ERK-1/2) mitogen-activated protein kinase pathway. Inhibition of the upstream kinase MEK-1/2 with U0126 attenuates the phosphorylation of both ERK-1/2 and HSF1, and significantly enhances drug cytotoxicity. From these data we propose a unique model whereby the ERK-1/2-dependent activation of HSF1 promotes chemotherapeutic resistance to benzimidazole carbamates. Therefore, targeting the ERK-1/2 signaling cascade is a potential strategy for HSF1 inhibition and a means of enhancing the cytotoxicity of these agents.

  15. Vasodilator activity of 2-(p-chloro-alpha-hydroxybenzyl)benzimidazole (HBBPC) on femoral vascular bed of the rabbit. (United States)

    Demenge, P; Silice, C; Luu Duc, C; Carraz, G


    The effects of 2-(p-chloro-alpha-hydroxybenzyl) benzimidazole HCl (HBBPC) have been studied on the femoral peripheral resistance (i.v. route) and only femoral blood flow (local i.a. injection), in comparison with other vasodilators, i.e., sodium nitroprusside, dihydralazine and piribedil. The vasomotor activity of HBBPC, namely, decreased peripheral resistance and increased femoral blood flow, seems interesting because it begins after pressure has returned to normal. This substance is likely to induce a vasoconstriction in other areas (increased femoral blood flow with decreased peripheral resistance without a fall of blood pressure).

  16. Ethyl 2-(4-nitrophenyl-1-[3-(2-oxopyrrolidin-1-ylpropyl]-1H-benzimidazole-5-carboxylate

    Directory of Open Access Journals (Sweden)

    Yeong Keng Yoon


    Full Text Available In the title compound, C23H24N4O5, the essentially planar benzimidazole ring system [maximum deviation = 0.008 (2 Å] forms a dihedral angle of 39.22 (7° with the attached nitrobenzene ring. The pyrrolidin-2-one ring adopts an envelope conformation with a C atom as the flap. In the crystal, molecules are connected by C—H...O interactions, forming sheets propagating in (011. The crystal packing also features weak π–π stacking interactions [centroid–centroid = 3.6746 (12 Å].

  17. Influence of the side chain next to C-terminal benzimidazole in opioid pseudopeptides containing the Dmt-Tic pharmacophore. (United States)

    Balboni, Gianfranco; Trapella, Claudio; Sasaki, Yusuke; Ambo, Akihiro; Marczak, Ewa D; Lazarus, Lawrence H; Salvadori, Severo


    To improve the structure-activity studies of the lead delta opioid agonist H-Dmt-Tic-Asp*-Bid, we synthesized and pharmacologically characterized a series of analogues in which the side chain next to 1H-benzimidazole-2-yl (Bid) was substituted by those endowed with different chemical properties. Interesting results were obtained: (1) only Gly, Ala, and Asp resulted in delta agonism, (2) Phe yielded delta antagonism, (3) and all other residues except Glu (devoid of any activity) gave mu agonism.

  18. Effect of diphenyl, o-phenylphenol and 2-(4-thiazoyl) benzimidazole on growth of tetrahymena pyriformis

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, K.; Yoshikawa, H.; Sugitani, A.; Kawai, M.


    Diphenyl (DP), o-phenylphenol (OPP), 2-(4-thiazoyl) benzimidazole (TBZ), are used as fungicides for citrus fruits. The acute toxicity of these compounds has been established for whole animals. However, additional information as to the cytotoxic effect of these fungicides is required. The ciliated protozoan, Tetrahymena pyriformis, is a single cell organism easily grown in an axenic medium, and has nutritional requirements similal to those of higher animals. Therefore, T. pyriformis has been used as a tool for the determination of the toxicity of food colors and heavy metals. The authors report the toxicity of DP, OPP and TBZ using T. pyriformis as a model test system.

  19. Syntheses of Benzimidazoles, Quinoxalines and 3,3-Dihydro 1 H-1,5-benzodiazepines Starting from o-Phenylenediamine

    Institute of Scientific and Technical Information of China (English)

    CUI Yong; TANG Xiu-Bo; SHAO Chang-Xing; LI Ji-Tai; SUN Wen-Hua


    A series of benzo-fused heteroaromatic compounds with 5-, 6- and 7-membered rings, such as benzimidazole,quinoxaline and 1H-1,5-benzodiazepine derivatives, were synthesized through condensation reaction of o-phenyl-enediamine with aryl aldehydes or ketones. The experimental conditions were carefully examined, and the products were characterized by 1H NMR, 13C NMR, MS, IR and elemental analyses. In addition, the structure of a benzodiazaepine derivative with 7-membered ring was confirmed by single crystal X-ray diffraction analysis.

  20. Graphene oxide-based benzimidazole-crosslinked networks for high-performance supercapacitors (United States)

    Cui, Yi; Cheng, Qian-Yi; Wu, Haiping; Wei, Zhixiang; Han, Bao-Hang


    The synthesis of graphene oxide (GO)-based benzimidazole-crosslinked network (GOBIN) materials is presented. These materials are prepared by the covalent crosslinking of GO sheets using a condensation reaction between the carboxylic acid moieties on the GO surface and the o-aminophenyl end groups of 3,3'-diaminobenzidine (or 1,2,4,5-benzenetetraamine tetrahydrochloride). An efficient one-pot catalyst- and template-free synthesis was performed. The obtained porous GO-based materials possess a Brunauer-Emmett-Teller specific surface area ranging from 260 to 920 m2 g-1. Electrochemical testing indicates that the GOBIN materials display a specific capacitance up to 370 F g-1 at a current density of 0.1 A g-1 and about 90% of the original capacitance is retained after 5000 cycles at a current density of 3 A g-1. Therefore, GOBIN materials can be employed as promising electrode materials for high-performance supercapacitors with outstanding cycling stability. Furthermore, owing to their significantly high specific surface area, these materials also show hydrogen uptake (up to 1.24 wt%, at 77 K and 1.0 bar) and carbon dioxide capture (up to 14.2 wt%, at 273 K and 1.0 bar) properties. As a result, these GO-based porous materials improve both the supercapacitor performance and gas sorption property, which demonstrate an excellent performance in the practical application of energy storage.The synthesis of graphene oxide (GO)-based benzimidazole-crosslinked network (GOBIN) materials is presented. These materials are prepared by the covalent crosslinking of GO sheets using a condensation reaction between the carboxylic acid moieties on the GO surface and the o-aminophenyl end groups of 3,3'-diaminobenzidine (or 1,2,4,5-benzenetetraamine tetrahydrochloride). An efficient one-pot catalyst- and template-free synthesis was performed. The obtained porous GO-based materials possess a Brunauer-Emmett-Teller specific surface area ranging from 260 to 920 m2 g-1. Electrochemical testing

  1. A comprehensive approach to the determination of two benzimidazoles in environmental samples. (United States)

    Wagil, Marta; Maszkowska, Joanna; Białk-Bielińska, Anna; Stepnowski, Piotr; Kumirska, Jolanta


    Among the various pharmaceuticals regarded as emerging pollutants, benzimidazoles--represented by flubendazole and fenbendazole--are of particular concern because of their large-scale use in veterinary medicine and their health effects on aquatic organisms. For this reason, it is essential to have reliable analytical methods which can be used to simultaneously monitor their appearance in environmental matrices such as water, sediment and tissue samples. To date, however, such methods relating to these three matrices have not been available. In this paper we present a comprehensive approach to the determination of both drugs in the mentioned above matrices using liquid chromatography-ion trap mass spectrometry (LC-MS/MS). Special attention was paid to the sample preparation step. The optimal extraction methods were further validated by experiments with spiked water, sediment and fish tissue samples. Matrix effects were established. The following absolute recoveries of flubendazole and fenbendazole were achieved: 96.2% and 95.4% from waters, 103.4% and 98.3% from sediments, and 98.3% and 97.6% from fish tissue samples, respectively. Validation of the LC-MS/MS methods enable flubendazole and fenbendazole to be determined with method detection limits: 1.6 ng L(-1) and 1.7 ng L(-1) in water samples; 0.3 ng g(-1) for both compounds in sediment samples, and 3.3 ng g(-1) and 3.5 ng g(-1) in tissue samples, respectively. The proposed methods were successfully used for analysing selected pharmaceuticals in real samples collected in northern Poland. There is first data on the concentration in the environment of the target compounds in Poland.

  2. Separation of lanthanides and actinides(III) using tridentate benzimidazole, benzoxazole and benzothiazole ligands

    Energy Technology Data Exchange (ETDEWEB)

    Drew, M.G.B.; Hudson, M.J.; Iveson, P.B.; Vaillant, L.; Youngs, T.G.A. [Reading Univ. (United Kingdom). Dept. of Chemistry; Hill, C.; Madic, Ch. [CEA Valrho, Dir. de l' Energie Nucleaire, Departement RadioChimie et Procedes, Service de Chimie des Procedes de Separation (DEN/DRCP/SCPS/LCSE), 30 - Marcoule (France)


    The ability of new hydrophobic tridentate ligands based on 2,6-bis(benzimidazole-2-yl)pyridine, 2,6-bis(benzoxazole-2-yl)pyridine and 2,6-bis(benzothiazole-2-yl)pyridine to selectively extract americium(III) from europium(III) was measured. The most promising ligand - 2,6-bis(benzoxazole-2-yl)-4-(2-decyl-1-tetra-decyl-oxy)pyridine L{sup 9} was found to give separation factors (SF{sub Am/Eu}) of up to 70 when used to extract cations from 0.02-0.10 M HNO{sub 3} into TPH in synergy with 2-bromo-decanoic acid. Six structures of lanthanide complexes with 2,6-bis(benzoxazole-2-yl)pyridine L{sup 6} were then determined to evaluate the types of species that are likely to be involved in the separation process. Three structural types were observed, namely [LnL{sup 6}(NO{sub 3}){sub 3}(H{sub 2}O){sub 2}), 11-coordinate only for La, [LnL{sup 6}(NO{sub 3})3 (CH{sub 3}CN)], 10-coordinate for Pr, Nd and Eu and [LnL{sup 6}(NO{sub 3}){sub 3}(H{sub 2}O)], L 10-coordinate for Eu and Gd. Quantum Mechanics calculations were carried out on the tridentate ligands to elucidate the conformational preferences of the ligands in the free state and protonated and di-protonated forms and to assess the electronic properties of the ligands for comparison with other ter-dentate ligands used in lanthanide/actinide separation processes. (authors)

  3. A Cu (NO3)2.3H2O catalysed facile synthesis of substituted 4(3H)-quinazolinones and benzimidazoles

    Indian Academy of Sciences (India)

    G A N K Durgareddy; R Ravikumar; S Ravi; Srinivas R Adapa


    One pot synthesis of alkyl, aryl, heteroaryl mono(2)substituted 4(3H)-quinazolinones and 2-aryl or heteroaryl, 1-arylmethyl or heteroarylmethyl -1H-benzimidazoles using a water soluble Cu (NO3)2.3H2O catalyst at room/ambient temperature in excellent yield.

  4. Magnetic Ionic Liquid [bmim][FeCl4] as an Efficient Catalyst for the Synthesis of 2-Aryl Benzimidazoles and 2-Aryl Benzothiazoles Derivatives

    Directory of Open Access Journals (Sweden)

    Soheil Sayyahi


    Full Text Available The magnetic ionic liquid (MIL 1-butyl-3-methylimidazolium tetrachloro ferrate(III ([bmim][FeCl4] sufficiently catalyzes the one-pot condensation of 1,2 diaminobenzene or 2-aminobenzenethiol with different aromatic aldehydes producing benzimidazoles and benzothiazoles drivatives, respectively. The MIL showed high performance resulting great yields with appropriate reaction time.

  5. Microwave Synthesis, Characterization and DNA-binding Properties of a New Cobalt(Ⅱ) Complex with 2,6-Bis(benzimidazol-2-yl)pyridine

    Institute of Scientific and Technical Information of China (English)

    Nian Yuan TAN; Xiao Ming XIAO; Ze Lin LI; Takeko MATSUMURA-INOUE


    A new cobalt(Ⅱ) complex with tridentate ligand 2, 6-bis (benzimidazol- 2-yl)pyridine has been synthesized by microwave irradiation method and characterized by elemental analysis, electrochemical and spectral methods. The binding of the complex with calf thymus DNA has also been investigated by absorption and fluorescence spectra.

  6. A benzimidazole derivative (RCB20) in vitro induces an activation of energetic pathways on Taenia crassiceps (ORF strain) cysticerci. (United States)

    Fraga, Carolina Miguel; da Costa, Tatiane Luiza; de Castro, Ana Maria; Reynoso-Ducoing, Olivia; Ambrosio, Javier; Hernández-Campos, Alicia; Castillo, Rafael; Vinaud, Marina Clare


    Human cysticercosis caused by Taenia crassiceps is unusual; however, it is an useful experimental model for cysticercosis studies. Benzimidazole derivatives are important antihelminthic drugs widely used against helminths. A novel compound 6-chloro-5-(1-naphthyloxy) -2-(trifluoromethyl)-1H-benzimidazole (RCB20) is a benzimidazole derivative less polar and more lipophilic. The aim of this study was to detect the effect of the RCB20 on the in vitro energetic metabolism of T. crassiceps cysticerci. For this, products of the metabolism both produced and secreted/excreted (S/E) by the parasite were detected through spectrophotometry and high performance liquid chromatography after exposure to 6.5 and 13 μM of RCB20 and albendazole sulfoxide (ABZSO). There was a gradual increase in the concentrations of glucose not uptaken by parasites exposed to both concentrations RCB20 and ABZSO. There was a higher concentration of all the organic acids related to the tricarboxilic acid cycle int the parasites exposed to RCB20. The structural differences between RCB20 and ABZSO result in different targets within the parasite and in a greater induction of the energetic pathways, such as the glycolysis and the TCA cycle. RCB20 is a good candidate as a substitute for anthelminthic benzimidazoles due to a differentiated site of action with similar outcome.

  7. Nickel Oxide Nanoparticle-Deposited Silica Composite Solid-Phase Extraction for Benzimidazole Residue Analysis in Milk and Eggs by Liquid Chromatography-Mass Spectrometry. (United States)

    Sun, Huan; Yu, Qiong-Wei; He, Hai-Bo; Lu, Qian; Shi, Zhi-Guo; Feng, Yu-Qi


    A novel nickel oxide nanoparticle-deposited silica (SiO2@NiO) composite was prepared via liquid-phase deposition (LPD) and then employed as a solid-phase extraction (SPE) sorbent. When the SPE was coupled with liquid chromatography-electrospray ionization mass spectrometry (LC-ESI/MS) analysis, an analytical platform for the sensitive determination of benzimidazole residues in egg and milk was established. The limits of detection of nine benzimidazoles were in the range of 0.8-2.2 ng/mL in milk and 0.3-2.1 ng/g in eggs, respectively, which was 5-10 times superior to the methods with other adsorbents for SPE. The recoveries of nine benzimidazoles spiked in milk and egg ranged from 70.8 to 118.7%, with relative standard deviations (RSDs) being less than 18.9%. This work presented the excellent extraction performance of NiO on benzimidazoles for the first time, and the applicability of the LPD technique used as sorbents for trace analysis in complex matrices was also demonstrated.

  8. Crystal structure of 1,3-bis(4-methylbenzyl-1H-1,3-benzimidazol-3-ium bromide monohydrate

    Directory of Open Access Journals (Sweden)

    Sevim Türktekin Çelikesir


    Full Text Available In the title hydrated symetrically substituted 1,3-bis(4-methylbenzylbenzimidazolium salt, C23H23N2+·Br−·H2O, the dihedral angles between the benzimidazole ring system (r.m.s. deviation = 0.003 Å and the pendant benzene rings are 73.18 (16 and 77.52 (16°. Both benzene rings lie to the same side of the benzimidazole ring system, giving the cation an overall U-shape. In the crystal, the cation is linked to the water molecule by a short C—H...O hydrogen bond and the water molecule forms O—H...Br hydrogen bonds. Together, these interactions lead to [010] chains. The packing is consolidated by C—H...Br hydrogen bonds and aromatic π–π stacking interactions [centroid–centroid distances = 3.5401 (17 and 3.8815 (18 Å], generating a three-dimensional network.

  9. (E-1,2-Bis(1-propyl-5,6-dimethyl-1H-benzimidazol-2-ylethene

    Directory of Open Access Journals (Sweden)

    Joseph A. Potenza


    Full Text Available In the title compound, C26H32N4, the essentially planar (r.m.s. deviations of 0.0053 and 0.0242 Å benzimidazole fragments are trans with respect to a central ethene fragment, and are canted in opposite directions by 2.78 (6 and 5.87 (6° with respect to the ethene plane, giving the molecule a propeller conformation. The terminal ethyl fragments of the pendant n-propyl groups protrude to either side of the benzimidazole planes. Overall, the molecule exhibits a pseudo-center of symmetry at the mid-point of the ethene fragment. Both π–π stacking and typical C—H...π interactions are notably absent, as are intermolecular hydrogen bonds. When viewed along the a axis, the structure appears as criss-crossed layers of molecules with the planar fragments separated along the c-cell direction by the protruding ethyl groups.

  10. The efficacy of fenbendazole and albendazole against immature and adult stages of benzimidazole-resistant sheep trichostrongylids. (United States)

    Gunawan, M; Sangster, N C; Kelly, J D; Griffin, D; Whitlock, H V


    The efficacy of two recently introduced benzimidazole anthelmintics, albendazole and fenbendazole, was determined for six-day, 10-day and adult stages of resistant strains of Haemonchus contortus and Trichostrongylus colubriformis. Albendazole, at 3.8 mg/kg reduced H contortus worm counts by 92.4, 70.8 and 67.1 per cent while fenbendazole, at 5.0 mg/kg, reduced worm burdens by 51.7, 95.5 and 93.4 per cent against six-, 10- and 25-day-old parasites respectively. For T colubriformis, the corresponding reductions with albendazole were 97.7, 95.8 and 64.9 per cent and for fenbendazole 29.0, 66.3 and 33.4 per cent. Compared with susceptible strains of H contortus and T colubriformis, for which therapeutic doses of benzimidazole anthelmintics are generally highly active against all stages of development, the present results show that these drugs do not have a uniform level of activity against all developmental stages of resistant strains.

  11. The ternary metal mixed ligand complexes formed by benzimidazole and N, N-bis(2-hydroxyethyl) glycine

    Institute of Scientific and Technical Information of China (English)

    贺小凤; 龙腊生; 毋福海; 乐学义; 陈小明; 计亮年; 周忠远


    The stability constants of the ternary M(Bic)(Bzim)+ complexes, where M2+=Cu2+, Ni2+ or Zn2+, Bic-=the anion of N, N-bis(2-hydroxyethyl) glycine and Bzim = benzimidazole, were determined by potentiometric pH titration in aqueous solution. One of them (M2+ = Cu2+) was also separately determined by spectrophotometry. The results show that these ternary complexes are stabler than expected on statistical grounds. The enhanced stability of the ternary M(Bic) (Bzim)+ complexes is attributed to the πA-πB cooperative effect between Bic- and benzimidazole. Besides, compared with Cu(Bic) (Bzim)+ and Ni(Bic) (Bzim)+, the ternary Zn(Bic)(Bzim)+ complex has relatively high stability. The crystal structure of [Cu(Bic)(Bzim)]ClO4 was determined by single crystal X-ray diffraction techniques. The copper atom has a trigonal-bipyramidal geometry, the basal plane is formed by an oxygen atom of the carboxylato group and two hydroxyl oxygen atoms, the apical position is occupied by a nitrogen a

  12. Syntheses and molecular structures of novel Ru(II) complexes with bidentate benzimidazole based ligands and their catalytic efficiency for oxidation of benzyl alcohol (United States)

    Dayan, Osman; Tercan, Melek; Özdemir, Namık


    Five bidentate ligands derived from quinoline-2-carboxylic acid, i.e. 2-(1H-benzimidazol-2-yl)quinoline (L1), 2-(1-benzyl-1H-benzimidazol-2-yl)quinoline (L2), 2-[1-(2,3,5,6-tetramethylbenzyl)-1H-benzimidazol-2-yl]quinoline (L3), 2-[1-(4-chlorobenzyl)-1H-benzimidazol-2-yl]quinoline (L4), and 2-[1-(4-methylbenzyl)-1H-benzimidazol-2-yl]quinoline (L5) were synthesized. Treatment of L1-5 with [RuCl2(p-cymene)]2 and KPF6 afforded six-coordinate piano-stool Ru(II) complexes, namely, [RuCl(L1)(p-cymene)]PF6 (C1), [RuCl(L2)(p-cymene)]PF6 (C2), [RuCl(L3)(p-cymene)]PF6 (C3), [RuCl(L4)(p-cymene)]PF6 (C4), and [RuCl(L5)(p-cymene)]PF6 (C5). Synthesized compounds were characterized with different techniques such as 1H and 13C NMR, FT-IR, and UV-vis spectroscopy. The solid state structure of L1 and C3 was confirmed by single-crystal X-ray diffraction analysis. The single crystal structure of C3 verified coordination of L3 to the Ru(II) center. The Ru(II) center has a pseudo-octahedral three legged piano stool geometry. The complexes C1-5 were tested as catalysts for the catalytic oxidation of benzyl alcohol to benzaldehyde in the presence of periodic acid (H5IO6) (Substrate/Catalyst/Oxidant = 1/0.01/0.5). The best result was obtained with C2 (3 h→90%).

  13. Structural and in vitro cytotoxicity studies on 1H-benzimidazol-2-ylmethyl-N-phenyl amine and its Pd(II) and Pt(II) complexes (United States)

    Abdel Ghani, Nour T.; Mansour, Ahmed M.


    [MLCl 2]· zH 2O (L = (1H-benzimidazol-2-ylmethyl)-N-phenyl amine; M = Pd, z = 0; M = Pt, z = 1) and [PdL(OH 2) 2]·2X·zH 2O (X = Br, I, NO 3, z = 0; X = SCN, z = 1) complexes were synthesized as potential anticancer compounds and characterized by elemental analysis, spectral and thermal methods. FT-IR and 1H NMR studies revealed that the benzimidazole L is coordinated to the metal ions via the pyridine-type nitrogen (N py) of the benzimidazole ring and secondary amino group (NH sec). Quantum mechanical calculations of energies, geometries, vibrational wavenumbers, and 1H NMR of the benzimidazole L and its complexes were carried out by density functional theory using B3LYP functional combined with 6-31G(d) and LANL2DZ basis sets. Natural bond orbitals (NBOs) and frontier molecular orbitals were performed at B3LYP/LANL2DZ level of theory. The synthesized ligand, in comparison to its metal complexes was screened for its antibacterial activity. The benzimidazole L is more toxic against the bacterium Staphylococcus aureus (MIC = 58 μg/mL) than the standard tetracycline (MIC = 82 μg/mL). The complexes showed cytotoxicity against breast cancer, Colon Carcinoma, and human heptacellular Carcinoma cells. The platinum complex ( 6) displays cytotoxicity (IC 50 = 12.4 μM) against breast cancer compared with that reported for cis-platin 9.91 μM.

  14. Benzimidazole-resistant gastrointestinal nematodes in indigenous Chiapas and Pelibuey sheep breeds from Chiapas, Mexico. (United States)

    Liébano-Hernández, E; González-Olvera, M; Vázquez-Peláez, C; Mendoza-de-Gives, P; Ramírez-Vargas, G; Peralta-Lailson, M; Reyes-García, M E; Osorio, J; Sánchez-Pineda, H; López-Arellano, M E


    Because of the natural adaptation of Mexican sheep, the aim of the present study was to identify the presence or absence of gastrointestinal parasitic nematodes (GIN) resistant to benzimidazole (BZ) in both Chiapas and Pelibuey sheep breeds on local farms. Both male and female GIN-infected grazing sheep of the two breeds were selected. Sheep faecal samples were collected to obtain infective larvae (L3). This evolving stage of the parasite was used for taxonomic identification of the genus, based on its morphological characteristics. BZ anthelmintic resistance was evaluated using a nematode-compound in vitro interaction bioassay and the allele-specific polymerase chain reaction technique to detect mutations of residues 198 and 200 on isotype 1 of the β-tubulin gene. Three BZ-based compounds (febendazole (FBZ), tiabendazole (TBZ) and albendazole (ABZ)) at concentrations of 1, 0.5, 0.25, 0.125, 0.062 and 0.03 mg/ml were used to estimate the anthelmintic efficacy and lethal dose (LD50, LD90 and LD99) of the drugs. Two parasitic nematodes, Haemonchus and Teladorsagia, were identified in both isolates. Also, the proportions of anthelmintic resistance identified in GIN of the two sheep breeds were 68% in isolates from the Chiapas breed and 71.8% in the Pelibuey breed. The specific lethal activity obtained with FBZ was higher than 90%. However, TBZ and ABZ showed a lethal activity lower than 50%. High variability in the discriminating dose values was found among the BZ drugs. For example, FBZ LD ranged from 0.01 to 1.20 mg/ml; on the other hand, TBZ and ABZ required a dose ranging from 0.178 to 759 mg/ml. In addition, amino acid changes of Phe (TTC) to Tyr (TAC) at codon 200 of the β-tubulin gene, showing resistance to BZ, and no changes at codon 198 Glu (GAA) to Ala (GCA) were observed for both isolates. These results confirmed the presence of a genetic mutation associated with BZ in both Chiapas and Pelibuey nematode isolates.

  15. Synthesis, interaction with DNA and antiproliferative activities of two novel Cu(II) complexes with Schiff base of benzimidazole (United States)

    Song, Wen-Ji; Cheng, Jian-Ping; Jiang, Dong-Hua; Guo, Li; Cai, Meng-Fei; Yang, Hu-Bin; Lin, Qiu-Yue


    Two novel copper(II) complexes with Schiff base of benzimidazole [Cu(L)Cl]2·CH3OH have been synthesized. HL1 (N-(benzimidazol-2-ymethyl)-5-chlorosalicylideneimine, C15H11ClN3O) and HL2 (N-(benzimidazol-2-ymethyl)-salicylideneimine, C15H12N3O) are ligands of complex (1) and complex (2), respectively. The complexes were characterized by elemental analysis, IR, UV-Vis, TGA and X-ray diffraction. Within the complexes, Cu(II) ions were four coordinated by two nitrogen atom of azomethine and imine, one phenolic oxygen atom from HL and one chloride atom. A distorted quadrilateral structure was formed. Complex (1) crystallized in the triclinic crystal system. Results showed that π-π stacking effect occurred due to the existence of aromatic ring from Schiff base and hydrogen bonding between methanol and adjacent atoms. The DNA binding properties of the complexes were investigated by electronic absorption spectra, fluorescence spectra and viscosity measurements. Results indicated that complexes bound to DNA via partial intercalation mode. The DNA binding constants Kb/(L mol-1) were 1.81 × 104 (1), 1.37 × 104 (2), 6.27 × 103 (HL1) and 3.14 × 103 (HL2) at 298 K. The title complexes could quench the emission intensities of EB-DNA system significantly. The results of agarose gel electrophoresis indicated complex (1) could cleave supercoiled DNA through the oxidative mechanism. The inhibition ratios revealed that complex (1) and HL1 had strong antiproliferative activities against human breast cancer cells (MCF-7) lines and human colorectal cancer cells (COLO205) lines in vitro. The antiproliferative activities of complex (1) against MCF-7 lines (IC50 = 16.9 ± 1.5 μmol L-1) and against COLO205 lines (IC50 = 16.5 ± 3.4 μmol L-1) is much stronger than that of HL1, which had the potential to develop anti-cancer drug.

  16. Proton conducting membranes based on benzimidazole sulfonic acid doped sulfonated poly(oxadiazole-triazole) copolymer for low humidity operation

    Energy Technology Data Exchange (ETDEWEB)

    Boaventura, M.; Mendes, A.; Madeira, L.M. [LEPAE - Laboratorio de Engenharia de Processos Ambiente e Energia, Faculdade de Engenharia da Universidade do Porto, Rua Dr. Roberto Frias s/n, 4200-465 Porto (Portugal); Gomes, D.; Nunes, S.P. [GKSS Research Centre Geesthacht GmbH, Max Planck Str. 1, D-21502, Geesthacht (Germany); Ponce, M.L.


    This work reports for the first time the preparation of sulphonated poly(oxadiazole-triazole) copolymer membranes doped with amphoteric molecule, 1H-benzimidazole-2-sulphonic acid and their characterisation as proton conductors at 120 C and low humidity. The membranes had not only high proton conductivities, up to 4 x 10{sup -3} S cm{sup -1} at 120 C and low relative humidity (5 and 10%), but also had good mechanical properties with a storage modulus of about 3 GPa at 300 C and high thermal stability with T{sub g} up to around 420 C. Because of their superior ion conducting and mechanical properties they have potential as a proton conducting membrane for fuel cell applications, in particular at high temperature and extremely low-humidity conditions. (Abstract Copyright [2008], Wiley Periodicals, Inc.)

  17. Comparative Studies on Conventional and Microwave Synthesis of Some Benzimidazole, Benzothiazole and Indole Derivatives and Testing on Inhibition of Hyaluronidase

    Directory of Open Access Journals (Sweden)

    Joachim Jose


    Full Text Available We have synthesized twelve 2-substituted benzimidazole, benzothiazole andindole derivatives using on both microwave irradiation and conventional heating methods.The microwave method was observed to be more beneficial as it provides an increase ofyield from 3% to 113% and a 95 to 98 % reduction in time. All compounds were tested bya stains-all assay at pH 7 and by a Morgan-Elson assay at pH 3.5 for hyaluronidaseinhibitory activity at a concentration of 100 μM. The most potent compound was 2-(4-hydroxyphenyl-3-phenylindole (12 with an IC50 value of 107 μM at both pH 7 and 3.5.

  18. Investigation of the apoptotic pathway induced by benzimidazole-oxindole conjugates against human breast cancer cells MCF-7. (United States)

    Lakshma Nayak, Vadithe; Nagaseshadri, Bobburi; Vishnuvardhan, M V P S; Kamal, Ahmed


    In our previous studies, benzimidazole-oxindole conjugates were synthesized and evaluated by National Cancer Institute (NCI) for their cytotoxic activity and the new molecules like 5c and 5p were considered as potential leads. These conjugates arrested the cell cycle at G2/M phase and inhibited tubulin polymerization. These observations prompted us to investigate the apoptotic mechanism induced by these lead molecules against human breast cancer cells (MCF-7). Studies like measurement of mitochondrial membrane potential (ΔΨm), generation of reactive oxygen species (ROS) and Annexin V-FITC assay revealed that these compounds induced mitochondrial mediated (intrinsic apoptotic pathway) apoptosis in human breast cancer cells. It was further confirmed by western blot analysis of pro apoptotic protein Bax, anti apoptotic protein Bcl-2, cytochrome c release, caspase-9 activity and cleavage of PARP.

  19. Benzimidazole-Based Quinazolines: In Vitro Evaluation, Quantitative Structure-Activity Relationship, and Molecular Modeling as Aurora Kinase Inhibitors. (United States)

    Sharma, Alka; Luxami, Vijay; Saxena, Sanjai; Paul, Kamaldeep


    A series of benzimidazole-based quinazoline derivatives with different substitutions of primary and secondary amines at the C2 position (1-12) were evaluated for their Aurora kinase inhibitory activities. All compounds except for 3 and 6 showed good activity against Aurora kinase inhibitors, with IC50 values in the range of 0.035-0.532 μM. The ligand efficiency (LE) of the compounds with Aurora A kinase was also determined. The structure-activity relationship and the quantitative structure-activity relationship revealed that the Aurora inhibitory activities of these derivatives primarily depend on the different substitutions of the amine present at the C2 position of the quinazoline core. Molecular docking studies in the active binding site also provided theoretical support for the experimental biological data acquired. The current study identifies a novel class of Aurora kinase inhibitors, which can further be used for the treatment of cancer.

  20. An efficient synthesis of 3'-indolyl substituted pyrido[1,2-]benzimidazoles as potential antimicrobial and antioxidant agents

    Indian Academy of Sciences (India)

    Harshad G Kathrotiya; Manish P Patel


    A new class of indole-based pyrido[1,2-]benzimidazole derivatives 4a-r have been synthesized by one-pot cyclocondensation reaction of 2-phenyl-1-indole-3-carboxaldehyde 1a-i, malononitrile 2 and 2-cyanomethylbenzimidazole 3a-b in the presence of catalytic amount of NaOH. In vitro antimicrobial activity of the synthesized compounds were investigated against a representative panel of pathogenic strains specifically three Gram-positive bacteria (Streptococcus pneumoniae, Clostridium tetani, Bacillus subtilis), three Gram-negative bacteria (Salmonella typhi, Vibrio cholerae, Escherichia coli) and two fungi (Aspergillus fumigatus, Candida albicans) using broth microdilution MIC (minimum inhibitory concentration) method. In vitro antioxidant activity was evaluated by ferric-reducing antioxidant power (FRAP) assay method. Compounds 4c, 4e, 4l and 4q have been found to be most efficient antimicrobial members while compounds 4h and 4p possess better ferric reducing antioxidant power.

  1. Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DNA-binding antimicrobial agents. (United States)

    Zhang, Ling; Addla, Dinesh; Ponmani, Jeyakkumar; Wang, Ao; Xie, Dan; Wang, Ya-Nan; Zhang, Shao-Lin; Geng, Rong-Xia; Cai, Gui-Xin; Li, Shuo; Zhou, Cheng-He


    A series of novel benzimidazole quinolones as potential antimicrobial agents were designed and synthesized. Most of the prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. The most potent compound 15m was membrane active and did not trigger the development of resistance in bacteria. It not only inhibited the formation of biofilms but also disrupted the established Staphylococcus aureus and Escherichia coli biofilms. It was able to inhibit the relaxation activity of E. coli topoisomerase IV at 10 μM concentration. Moreover, this compound also showed low toxicity against mammalian cells. Molecular modeling and experimental investigation of compound 15m with DNA suggested that this compound could effectively bind with DNA to form a steady 15m-DNA complex which might further block DNA replication to exert the powerful bioactivities.

  2. Low power optical limiting studies on nanocrystalline benzimidazole thin films prepared by modified liquid phase growth technique

    Indian Academy of Sciences (India)

    P A Praveen; S P Prabhakaran; R Ramesh Babu; K Sethuraman; K Ramamurthi


    In the present work, benzimidazole (BMZ), a well known nonlinear optical material, thin films were deposited using the modified liquid phase growth technique at different solution temperatures. The prepared samples were subjected to spectral, structural and surface analyses. Linear optical properties and third-order optical nonlinearity of the deposited BMZ thin films were analysed using UV–visible–NIR spectrum and -scan technique, respectively. The experimental results show that the BMZ films exhibit reverse saturable absorption and positive nonlinearity at 650 nm CW laser of power 5 mW. The measured third-order nonlinear susceptibility of the films is about 10−10 esu. Optical limiting studies were performed using the same laser source and the potentiality of the BMZ films is reported.

  3. Benzimidazole-functionalized Zr-UiO-66 nanocrystals for luminescent sensing of Fe3+ in water (United States)

    Dong, Yingying; Zhang, Hanzhuo; Lei, Fan; Liang, Mei; Qian, Xuefeng; Shen, Peilian; Xu, Hui; Chen, Zhihui; Gao, Junkuo; Yao, Juming


    Zr-based MOF structure UiO-66 exhibits unprecedented high thermal and chemical stability, making it to be one of the most used MOFs in various applications. Yet, the poor photoluminescent (PL) properties of UiO-66 limit its applications in luminescent sensing. Herein, a new benzimidazole-functionalized UiO-66 nanocrystal (UiO-66-BI) was successfully fabricated via microwave synthesis. UiO-66-BI displayed octahedral nanocrystal morphology with a diameter smaller than 200 nm and could disperse well in water and common organic solvents. UiO-66-BI demonstrated extended optical absorption in the visible-light region and efficiently improved PL emission compared with UiO-66 pristine. The sensing properties of UiO-66-BI nanocrystals towards different ions were studied, and the results demonstrated that UiO-66-BI showed excellent selective luminescent sensing of Fe3+ ions in water.

  4. Design, synthesis and biological evaluation of novel benzimidazole-2-substituted phenyl or pyridine propyl ketene derivatives as antitumour agents. (United States)

    Wu, Lin-tao; Jiang, Zhi; Shen, Jia-jia; Yi, Hong; Zhan, Yue-chen; Sha, Ming-quan; Wang, Zhen; Xue, Si-tu; Li, Zhuo-rong


    A series of novel benzimidazole-2-subsituted phenyl or pyridine propyl ketene derivatives were designed and synthesized. The biological activities of these derivatives were then evaluated as potential antitumour agents. These compounds were assayed for growth-inhibitory activity against HCT116, MCF-7 and HepG2 cell lines in vitro. The IC50 values of compounds A1 and A7 against the cancer cells were 0.06-3.64 μM and 0.04-9.80 μM, respectively. Their antiproliferative activities were significantly better than that of 5-Fluorouracil (IC50: 56.96-174.50 μM) and were close to that of Paclitaxel (IC50: 0.026-1.53 μM). The activity of these derivatives was over 100 times more effective than other reported structures of chalcone analogues (licochalcone A). A preliminary mechanistic study suggested that these compounds inhibit p53-MDM2 binding. Compounds A1, A7 and A9 effectively inhibited tumour growth in BALB/c mice with colon carcinoma HCT116 cells. The group administered 200 mg/kg of compound A7 showed a 74.6% tumour growth inhibition with no signs of toxicity at high doses that was similar to the inhibition achieved with the 12.5 mg/kg irinotecan positive control (70.2%). Therefore, this class of benzimidazole-2-subsituted phenyl or pyridine propyl ketene derivatives represents a promising lead structure for the development of possible p53-MDM2 inhibitors as new antitumour agents.

  5. A Green Route for the One-Pot Synthesis of 1,2-Disubstituted Benzimidazoles Using Iron(Ill) Phosphate under Solventless Conditions%A Green Route for the One-Pot Synthesis of 1,2-Disubstituted Benzimidazoles Using Iron(Ill) Phosphate under Solventless Conditions

    Institute of Scientific and Technical Information of China (English)

    Behbahani, F.K.; Ziaei, Parisa


    1,2-Disubstituted benzimidazoles are selectively synthesized in high yields under extremely mild conditions via the condensation of o-phenylenediamine derivatives with aldehyde derivatives using catalytic amount of iron(Ⅲ) phosphate under solventfree conditions. The use of readily available iron(Ⅲ) phosphate as a reusable and recyelable catalyst makes this process quite simple, convenient, and environment-friendly.

  6. A green and efficient protocol for the synthesis of quinoxaline, benzoxazole and benzimidazole derivatives using heteropolyanion-based ionic liquids: as a recyclable solid catalyst. (United States)

    Vahdat, Seyed Mohammad; Baghery, Saeed


    In this paper, we introduce two nonconventional ionic liquid compounds which are composed of propane sulfonate functionalized organic cations and heteropolyanions as green solid acid catalysts for the highly efficient and green synthesis of 2,3-disubstitutedquinoxaline derivatives. These ionic liquids are in the solid state at room temperature and the synthesis is carried out via the one-pot condensation reaction of various o-phenylenediamine with 1,2-diketone derivatives. Benzoxazole and benzimidazole derivatives were also synthesized by these novel catalysts via the one-pot condensation from reaction orthoester with o-aminophenol (synthesis of benzoxazole derivatives) and ophenylenediamine (synthesis of benzimidazole derivatives). All experiments successfully resulted in the desired products. The described novel synthesis method has several advantages of safety, mild condition, high yields, short reaction times, simplicity and easy workup compared to the traditional method of synthesis.

  7. Anchoring of Cu(II) onto surface of porous metal-organic framework through post-synthesis modification for the synthesis of benzimidazoles and benzothiazoles (United States)

    Kardanpour, Reihaneh; Tangestaninejad, Shahram; Mirkhani, Valiollah; Moghadam, Majid; Mohammadpoor-Baltork, Iraj; Zadehahmadi, Farnaz


    Efficient synthesis of various benzimidazoles and benzothiazoles under mild conditions catalyzed by Cu(II) anchored onto UiO-66-NH2 metal organic framework is reported. In this manner, first, the aminated UiO-66 was modified with thiophene-2-carbaldehyde and then the prepared Schiff base was reacted with CuCl2. The prepared catalyst was characterized by FT-IR, UV-vis, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), N2 adsorption, inductively coupled plasma atomic emission spectroscopy (ICP-AES) and field emission scanning electron microscopy (FE-SEM). The UiO-66-NH2-TC-Cu was applied as a highly efficient catalyst for synthesis of benzimidazole and benzothiazole derivatives by the reaction of aldehydes with 1,2-diaminobenzene or 2-aminothiophenol. The Cu(II)-containing MOF was reused several times without any appreciable loss of its efficiency.

  8. Synthesis, DNA binding ability and anticancer activity of 2-heteroaryl substituted benzimidazoles linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates. (United States)

    Kamal, Ahmed; Pogula, Praveen Kumar; Khan, Mohammed Naseer Ahmed; Seshadri, Bobburi Naga; Sreekanth, Kokkonda


    As a continuation of our efforts to develop the benzimidazole-PBD conjugates as potential anticancer agents, a series of heteroaryl substituted benzimidazole linked PBD conjugates has been synthesized and evaluated for their anticancer potential in 60 human cancer cell lines. Most of the compounds exhibited promising anticancer activity and interestingly, compounds 4c and 4d displayed significant activity in most of the cell lines tested. Whereas, compound 4e showed selectivity in renal cancer cells with GI50 values of <10 and 70 nM against RXF 393 and UO-31 cell lines, respectively. Further, these compounds also showed significant DNA-binding affinity by thermal denaturation study using duplex form of calf thymus (CT) DNA.

  9. The effect of single and divided dose administration on the efficacy of fenbendazole against adult stages of benzimidazole resistant sheep trichostrongylids. (United States)

    Sangster, N C; Whitlock, H V; Kelly, J D; Gunawan, M; Hall, C A


    Sheep infected with benzimidazole resistant strains of Haemonchus contortus and Trichostrongylus colubriformis were used to compare the anthelmintic efficacy of fenbendazole given as a single dose or administered in a divided dose regime over five days. Statistical analysis showed no significant difference between the two methods of administration for H contortus. On the other hand, divided dose fenbendazole was significantly less effective than single doses against adult T colubriformis at dose rates of 5 and 7.5 mg/kg. In the case of H contortus a highly significant correlation coefficient between post treatment egg counts and worm counts (r = 0.789) was obtained. This suggests that reduction in faecal egg output following drug treatment would provide a useful field indication of anthelmintic performance of fenbendazole (and possibly related compounds) against benzimidazole resistant strains of this parasite.

  10. Synthesis and SAR of novel, potent and orally bioavailable benzimidazole inhibitors of poly(ADP-ribose) polymerase (PARP) with a quaternary methylene-amino substituent. (United States)

    Zhu, Gui-Dong; Gandhi, Viraj B; Gong, Jianchun; Thomas, Sheela; Luo, Yan; Liu, Xuesong; Shi, Yan; Klinghofer, Vered; Johnson, Eric F; Frost, David; Donawho, Cherrie; Jarvis, Ken; Bouska, Jennifer; Marsh, Kennan C; Rosenberg, Saul H; Giranda, Vincent L; Penning, Thomas D


    Poly(ADP-ribose) polymerases (PARPs) play significant roles in various cellular functions including DNA repair and control of RNA transcription. PARP inhibitors have been demonstrated to potentiate the effect of cytotoxic agents or radiation in a number of animal tumor models. Utilizing a benzimidazole carboxamide scaffold in which the amide forms a key intramolecular hydrogen bond for optimal interaction with the enzyme, we have identified a novel series of PARP inhibitors containing a quaternary methylene-amino substituent at the C-2 position of the benzimidazole. Geminal dimethyl analogs at the methylene-amino substituent were typically more potent than mono-methyl derivatives in both intrinsic and cellular assays. Smaller cycloalkanes such as cyclopropyl or cyclobutyl were tolerated at the quaternary carbon while larger rings were detrimental to potency. In vivo efficacy data in a B16F10 murine flank melanoma model in combination with temozolomide (TMZ) are described for two optimized analogs.

  11. Comparison of in vitro methods and faecal egg count reduction test for the detection of benzimidazole resistance in small strongyles of horses. (United States)

    Königová, A; Várady, M; Corba, J


    The objective of the study was to compare the in vitro egg hatch test (EHT), larval development test (LDT) and in vivo faecal egg count reduction test (FECR test) for the detection of benzimidazole resistance in equine strongyles. The presence of resistant or susceptible strongyle populations was determined in 25 stud farms using the in vivo FECR test and in vitro EHT. On the basis of the FECR values, resistance to fenbendazole was detected on 15 of the 25 farms (60%). The ED50 value (anthelmintic concentration producing 50% inhibition of hatching) for suspected resistant populations varied from 0.110 to 0.222 microg/ml thiabendazole (TBZ). Final LD50 values (anthelmintic concentration inhibiting development of 50% of eggs into L3 infective larvae) above 0.029 microg/ml TBZ in the in vitro larval development test on samples from 11 stud farms revealed the presence of populations of small strongyles suspected of being benzimidazole-resistant.

  12. cyclo-Tetra-μ-malato-κ16O,O′,O′′:O′′′-tetrakis[bis(1H-benzimidazole-κN3cobalt(II] eicosahydrate

    Directory of Open Access Journals (Sweden)

    Duan-Jun Xu


    Full Text Available The title compound, [Co4(C4H4O54(C7H6N28]·20H2O, consists of tetranuclear CoII complexes and disordered uncoordinated water molecules. The tetrameric complex molecule has overline{4} symmetry. While two benzimidazole molecules and a tridentate malate dianion coordinate a CoII ion, the carboxylate O atom from an adjacent malate dianion bridges the CoII ions to complete a distorted octahedral coordination geometry. The tridentate malate dianion chelates the CoII ion, and the chelate six- and five-membered rings show half-chair and envelope configurations, respectively. A face-to-face separation of 3.494 (9 Å between parallel benzimidazole ligands indicates the existence of π–π stacking between adjacent complexes. The crystal structure also involves N—H...O and O—H...O hydrogen bonds.

  13. DFT and electrochemical studies of tris(benzimidazole-2-ylmethyl)amine as an efficient corrosion inhibitor for carbon steel surface

    Energy Technology Data Exchange (ETDEWEB)

    Roque, Jacinto Morales [Facultad de Quimica, Universidad Nacional Autonoma de Mexico, Mexico D.F. 04510 (Mexico); Pandiyan, T. [Facultad de Quimica, Universidad Nacional Autonoma de Mexico, Mexico D.F. 04510 (Mexico)], E-mail:; Cruz, J. [Centro de Investigaciones Quimicas, Universidad Autonoma del Estado de Hidalgo, Unidad Universitaria, Km 4.5 Carretera Pachuca-Tulancingo, C.P. 42184 Pachuca-Hidalgo (Mexico); Garcia-Ochoa, E. [Centro de Investigacion en Corrosion, Universidad Autonoma de Campeche, Mexico, Av. Agustin Melgar s/n, Colonia Buenavista, San Francisco de Campeche, Cam. C.P. 24030 (Mexico)


    The corrosion inhibition properties of tris(benzimidazole-2-ylmethyl)amine (TBMA) were analyzed by DFT and electrochemical techniques such as polarization curves and electrochemical impedance spectroscopy (EIS). DFT results clearly show that TBMA posses corrosion inhibition properties by having a delocalization region (N{sub 1}=C{sub 2}=N{sub 3}) in the benzimidazole ring that gives up their {pi} electron density through its HOMO orbital to the metal LUMO to form a adsorption layer over the metallic surface; this has been proved by interacting the TBMA and its protonated structures with the surface of Fe{sub 13} cluster, showing that the protonated moiety adsorbs strongly on the iron surface than that of the neutral structure. Electrochemical impedance data demonstrate that the interface between the electrode and the TBMA solution decreases the charge capacitance and simultaneously increases the function of the charge/discharge of the interface, facilitating the formation of adsorption layer over the iron surface.

  14. A novel sodium iodide and ammonium molybdate co-catalytic system for the efficient synthesis of 2-benzimidazoles using hydrogen peroxide under ultrasound irradiation. (United States)

    Bai, Guo-Yi; Lan, Xing-Wang; Chen, Guo-Feng; Liu, Xiao-Fang; Li, Tian-Yu; Shi, Ling-Juan


    The reaction of aldehydes and o-phenylenediamine for the preparation of 2-benzimidazoles has been studied using hydrogen peroxide as an oxidant under ultrasound irradiation at room temperature in this paper. The combination of substoichiometric sodium iodide and ammonium molybdate as co-catalysts, together with using small amounts of hydrogen peroxide, makes this transformation very efficient and attractive under ultrasound. Thus, a mild, green and efficient method is established to carry out this reaction in high yield.

  15. Preparation of stir cake sorptive extraction based on polymeric ionic liquid for the enrichment of benzimidazole anthelmintics in water, honey and milk samples. (United States)

    Wang, Yulei; Zhang, Jie; Huang, Xiaojia; Yuan, Dongxing


    In this work, a new stir cake sorptive extraction (SCSE) using polymeric ionic liquid monolith as sorbent was prepared. The sorbent was obtained by in situ copolymerization of an ionic liquid, 1-allyl-3-methylimidazolium bis[(trifluoro methyl)sulfonyl]imide (AMII) and divinylbenzene (DB) in the presence of N,N-dimethylformamide. The influence of the content of ionic liquid and the porogen in the polymerization mixture on extraction performance was studied thoroughly. The physicochemical properties of the polymeric ionic liquid were characterized by infrared spectroscopy, elemental analysis, scanning electron microscopy and mercury intrusion porosimetry. The usefulness of SCSE-AMIIDB was demonstrated by the enrichment of trace benzimidazole anthelmintics. Several parameters affecting the extraction efficiency were investigated, and under the optimized conditions, a simple and effective method for the determination of trace benzimidazoles residues in water, milk and honey samples was established by coupling SCSE-AMIIDB with high performance liquid chromatography/diode array detection (SCSE-AMIIDB-HPLC/DAD). Results indicated that the limits of detection (S/N=3) for target compounds were 0.020-0.072 μg L(-1), 0.035-0.10 μg L(-1) and 0.026-0.076 μg L(-1) in water, milk and honey samples, respectively. In addition, an acceptable reproducibility was achieved by evaluating the repeatability and intermediate precision with relative standard deviations (RSD) of less than 9% and 11%, respectively. Finally, the established AMII-SCSE-HPLC/DAD method was successfully applied for the determination of benzimidazoles residues in milk, honey and environmental water samples. Recoveries obtained for the determination of benzimidazole anthelmintics in spiking samples ranged from 70.2% to 117.6%, with RSD below 12% in all cases.

  16. Structure-Bioactivity Relationship for Benzimidazole Thiophene Inhibitors of Polo-Like Kinase 1 (PLK1, a Potential Drug Target in Schistosoma mansoni.

    Directory of Open Access Journals (Sweden)

    Thavy Long


    Full Text Available Schistosoma flatworm parasites cause schistosomiasis, a chronic and debilitating disease of poverty in developing countries. Praziquantel is employed for treatment and disease control. However, its efficacy spectrum is incomplete (less active or inactive against immature stages of the parasite and there is a concern of drug resistance. Thus, there is a need to identify new drugs and drug targets.We show that RNA interference (RNAi of the Schistosoma mansoni ortholog of human polo-like kinase (huPLK1 elicits a deleterious phenotypic alteration in post-infective larvae (schistosomula or somules. Phenotypic screening and analysis of schistosomula and adult S. mansoni with small molecule inhibitors of huPLK1 identified a number of potent anti-schistosomals. Among these was a GlaxoSmithKline (GSK benzimidazole thiophene inhibitor that has completed Phase I clinical trials for treatment of solid tumor malignancies. We then obtained GSKs Published Kinase Inhibitor Sets (PKIS 1 and 2, and phenotypically screened an expanded series of 38 benzimidazole thiophene PLK1 inhibitors. Computational analysis of controls and PLK1 inhibitor-treated populations of somules demonstrated a distinctive phenotype distribution. Using principal component analysis (PCA, the phenotypes exhibited by these populations were mapped, visualized and analyzed through projection to a low-dimensional space. The phenotype distribution was found to have a distinct shape and topology, which could be elicited using cluster analysis. A structure-activity relationship (SAR was identified for the benzimidazole thiophenes that held for both somules and adult parasites. The most potent inhibitors produced marked phenotypic alterations at 1-2 μM within 1 h. Among these were compounds previously characterized as potent inhibitors of huPLK1 in cell assays.The reverse genetic and chemical SAR data support a continued investigation of SmPLK1 as a possible drug target and/or the prosecution of

  17. Ultrasound promoted and SiO2/CCl3COOH mediated synthesis of 2-aryl-1-arylmethyl-1-benzimidazole derivatives in aqueous media: An eco-friendly approach

    Indian Academy of Sciences (India)

    Brajesh Kumar; Kumari Smita; Brajendra Kumar; Luis Cumbal


    Ultrasonic irradiation is an efficient and innocuous technique of reagent activation for synthesizing organic compounds. First one-pot synthesis of 2-aryl-1-arylmethyl-1H- benzimidazole derivatives from o- phenylenediamine and an aromatic aldehyde in the presence of silica gel supported trichloroacetic acid (SiTCA) was carried out with excellent yields at 50°C by sonication. This method provided several advantages such as green solvent, inexpensive catalyst, simple experimental methodology, shorter reaction time and higher yield.

  18. Synthesis of a novel series of 4-arylpiperazinyl derivatives linked to a 2-(pyridin-3-yl)-1H-benzimidazole as new Delavirdine analogues

    Energy Technology Data Exchange (ETDEWEB)

    Pessoa-Mahana, David; Nunez, Andres; Espinosa, Christian; Mella-Raipn, Jaime [Pontificia Universidad Catolica de Chile, Santiago (Chile). Facultad de Quimica. Dept. de Farmacia; Pessoa-Mahana, Hernan [Universidad de Chile, Santiago (Chile). Facultad de Ciencias Quimicas. Dept. de Quimica Organica y Fisico-Quimica


    The synthesis of a series of substituted arylpiperazines linked to a 2-(pyridin-3-yl)-1H-benzo[d]imidazole scaffold through an alkylic linker is reported. The novel 1-(2-(4-arylpiperazin-1-yl)alkyl)-2-(pyridin-3-yl)-1H-benzimidazole derivatives are structurally related to the anti-HIV-1 drug Delavirdine and belong to the bis(heteroaryl)piperazines family (BHAPs), a well known HIV-1 reverse transcriptase inhibitors group. (author)

  19. Novel Ni(II) and Zn(II) complexes coordinated by 2-arylaminomethyl-1H-benzimidazole: Molecular structures, spectral, DFT studies and evaluation of biological activity (United States)

    Abdel-Ghani, Nour T.; Abo El-Ghar, Maha F.; Mansour, Ahmed M.


    [NiL1,2Cl2(OH2)3]·zH2O and [ZnL1,2(CH3CO2)2] (L1 = (1H-benzimidazol-2-ylmethyl)-N-phenyl amine, z = 0 and L2 = 2-[(1H-Benzimidazol-2-ylmethyl)-amino]-benzoic acid methyl ester, z = 1) complexes have been synthesized and characterized by a variety of physico-chemical techniques. The central Ni(II) ion is coordinated by only the pyridine-type nitrogen (Npy) of benzimidazole ring, three water molecules and two chlorido ligands forming a distorted octahedral geometry. Five coordinated zinc complexes were obtained, where the coordination sphere of zinc ion is made up of secondary amino group (NHsec), Npy and two acetate groups, one acts as a unidentate and the other as a bidentate. A theoretical DFT/UB3LYP method combined with LANL2DZ basis set shows that all the metal-ligand bonds are of the L → M type. Electronic structures have been calculated using TD-DFT method. The antibacterial activity of NiL2 complexes decreases by the introduction of COOCH3 group in the ortho-position of the aniline moiety.

  20. Preparation of stir cake sorptive extraction based on polymeric ionic liquid for the enrichment of benzimidazole anthelmintics in water, honey and milk samples

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yulei [State Key Laboratory of Marine Environmental Science, Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystem, College of the Environment and Ecology, Xiamen University, Siming Road, P.O. Box 1009, Xiamen 361005 (China); Zhang, Jie [Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences (China); Huang, Xiaojia, E-mail: [State Key Laboratory of Marine Environmental Science, Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystem, College of the Environment and Ecology, Xiamen University, Siming Road, P.O. Box 1009, Xiamen 361005 (China); Yuan, Dongxing [State Key Laboratory of Marine Environmental Science, Key Laboratory of the Ministry of Education for Coastal and Wetland Ecosystem, College of the Environment and Ecology, Xiamen University, Siming Road, P.O. Box 1009, Xiamen 361005 (China)


    Highlights: • A new polymeric ionic liquid-based monolith was prepared. • The monolith was used as the extractive medium of stir cake sorptive extraction. • The SCSE–AMIIDB can extract benzimidazole anthelmintics (BAs) effectively. • A combination of SCSE–AMIIDB–LD–HPLC/DAD was developed. • The combination was applied to monitor trace BAs in water, milk and honey samples. - Abstract: In this work, a new stir cake sorptive extraction (SCSE) using polymeric ionic liquid monolith as sorbent was prepared. The sorbent was obtained by in situ copolymerization of an ionic liquid, 1-allyl-3-methylimidazolium bis[(trifluoro methyl)sulfonyl]imide (AMII) and divinylbenzene (DB) in the presence of N,N-dimethylformamide. The influence of the content of ionic liquid and the porogen in the polymerization mixture on extraction performance was studied thoroughly. The physicochemical properties of the polymeric ionic liquid were characterized by infrared spectroscopy, elemental analysis, scanning electron microscopy and mercury intrusion porosimetry. The usefulness of SCSE–AMIIDB was demonstrated by the enrichment of trace benzimidazole anthelmintics. Several parameters affecting the extraction efficiency were investigated, and under the optimized conditions, a simple and effective method for the determination of trace benzimidazoles residues in water, milk and honey samples was established by coupling SCSE–AMIIDB with high performance liquid chromatography/diode array detection (SCSE–AMIIDB–HPLC/DAD). Results indicated that the limits of detection (S/N = 3) for target compounds were 0.020–0.072 μg L{sup −1}, 0.035–0.10 μg L{sup −1} and 0.026–0.076 μg L{sup −1} in water, milk and honey samples, respectively. In addition, an acceptable reproducibility was achieved by evaluating the repeatability and intermediate precision with relative standard deviations (RSD) of less than 9% and 11%, respectively. Finally, the established AMII

  1. Novel palladium(II) and platinum(II) complexes with 1H-benzimidazol-2-ylmethyl-N-(4-bromo-phenyl)-amine: structural studies and anticancer activity. (United States)

    Abdel Ghani, Nour T; Mansour, Ahmed M


    [MLCl(2)] (L = (1H-benzimidazol-2-ylmethyl)-N-(4-bromo-phenyl)-amine; M = Pd & Pt) and [PdL(OH(2))(2)]∙2X∙zH(2)O (X = Br, I, z = 2; X = SCN, z = 1; X = NO(3), z = 0) complexes have been synthesized as potential anticancer compounds and their structures were elucidated using elemental analysis, spectral, thermal analysis and X-ray powder diffraction. The benzimidazole (L) crystallizes in the space group P2(1)/c with a = 8.6660(3) Å, b = 16.6739(7) Å, c = 9.8611(4) Å and β = 113.505(3) ° and forms an infinite chain structure with a trans-zigzag type along the crystallographic axis "a", through the intermolecular H-bond. FT-IR and (1)H NMR studies revealed that the ligand L is coordinated to the metal ion via the pyridine-type nitrogen (N(py)) of the benzimidazole ring and secondary amino group (NH(sec)). Quantum mechanical calculations of energies, geometries, vibrational wavenumbers, and (1)H NMR of the benzimidazole L and its complexes were carried out by DFT/B3LYP method combined with 6-31G(d) and LANL2DZ basis sets. Natural bond orbital (NBO) analysis and frontier molecular orbitals (FMO) were performed at B3LYP/LANL2DZ level of theory. The benzimidazole L, in comparison to its metal complexes was screened for its antibacterial activity. The complexes showed cyctotoxic effects against human breast cancer (MCF7), hepatocarcinoma (HepG(2)) and colon carcinoma cells (HCT). The platinum complex (6) exhibited a moderate antitumor activity against MCF7 with IC(50) = 10.2 μM comparing to that reported for cis-platin 9.91 μM.

  2. Photodriven spin change of Fe(II) benzimidazole compounds anchored to nanocrystalline TiO(2) thin films. (United States)

    Xia, Hai-Long; Ardo, Shane; Narducci Sarjeant, Amy A; Huang, Sunxiang; Meyer, Gerald J


    Ferrous tris-chelate compounds based on 2-(2'-pyridyl)benzimidazole (pybzim) have been prepared and characterized for studies of spin equilibria in fluid solution and when anchored to the surface of mesoporous nanocrystalline (anatase) TiO(2) and colloidal ZrO(2) thin films. The solid state structure of Fe(pybzim)(3)(ClO(4))(2).CH(3)CN.H(2)O was determined by single-crystal X-ray diffraction at 110 K to be triclinic, P-1, a = 11.6873(18), b = 12.2318(12), c = 14.723(4) A, alpha = 89.864(13) degrees , beta = 71.430(17) degrees , gamma = 73.788(11) degrees , V = 1907.1(6) A(3), Z = 2, and R = 0.0491. The iron compound has a meridional FeN(6) distorted octahedral geometry with bond lengths expected for a low-spin iron center at 110 K. The visible absorption spectra of Fe(pybzim)(3)(2+) and Fe(pymbA)(3)(2+), where pymbA is 4-(2-pyridin-2-yl-benzimidazol-1-ylmethyl)-benzoic acid, in methanol solution were dominated by metal-to-ligand charge-transfer (MLCT) bands. Variable-temperature UV-visible absorption spectroscopy revealed dramatic changes in the extinction coefficient consistent with a high-spin ((1)A) left harpoon over right harpoon low-spin ((5)T) equilibrium. Thermodynamic parameters for the temperature-dependent spin equilibrium of Fe(pymbA)(3)(2+) in methanol were determined to be DeltaH(HL) = 3270 +/- 210 cm(-1) and DeltaS(HL) = 13.3 +/- 0.8 cm(-1) K(-1). The corresponding values for Fe(pybzimEE)(3)(2+), where pybzimEE is (2-pyridin-2-yl-benzimidazol-1-yl)-acetic acid ethyl ester, in acetonitrile solution were determined to be 3072 +/- 34 cm(-1)and 10.5 +/- 0.1 cm(-1) K(-1). The temperature-dependent effective magnetic moments of Fe(pybzimEE)(3)(2+) in acetonitrile solution were also quantified by the Evans method. Pulsed 532 nm light excitation of Fe(pybzim)(3)(2+) or Fe(pymbA)(3)(2+) in solution resulted in an immediate bleach of the MLCT absorption bands. Relaxation back to the equilibrium state followed a first-order reaction mechanism. Arrhenius analysis

  3. Adsorption of benzotriazole and benzimidazole from water over a Co-based metal azolate framework MAF-5(Co). (United States)

    Sarker, Mithun; Bhadra, Biswa Nath; Seo, Pill Won; Jhung, Sung Hwa


    Benzotriazole (BTA) and benzimidazole (BZI) are regarded as water pollutants because of their extensive uses in industry and appreciable water solubility. The adsorption of both BTA and BZI from water over a newly synthesized metal-organic framework, MAF-5(Co), was investigated and compared with zeolitic imidazole frameworks (ZIFs), such as ZIF-8(Zn) and ZIF-67(Co), as well as commercial activated carbon. MAF-5(Co) had the highest adsorption capacities for both BTA and BZI. The maximum adsorption capacities of MAF-5(Co) for BTA and BZI were 389 and 175mgg(-1), respectively. Hydrophobic and π-π interactions between the aromatic adsorbate BTA and MAF-5(Co) were suggested as a plausible mechanism. Based on the zeta potential of MAF-5(Co) and effects of pH on the BTA adsorption, electrostatic interactions between the MAF-5(Co) and BTA species might also affect the adsorption of BTA over MAF-5(Co). MAF-5(Co) can be recycled for adsorptive removal of BTA by simple ethanol washing. Therefore, MAF-5(Co) is suggested as a promising adsorbent for the removal of BTA and BZI from water.

  4. PCR diagnosis of benzimidazole-susceptibility or -resistance in natural populations of the small ruminant parasite, Teladorsagia circumcincta. (United States)

    Elard, L; Cabaret, J; Humbert, J F


    We have developed a new molecular tool for the diagnosis of the benzimidazole (BZ)-susceptibility or resistance in Teladorsagia circumcincta a nematode parasite of small ruminants. This tool is based on the use of the PCR and allows the genotyping of resistant (rr) or susceptible (rS and SS) adult worms or larvae. By using four primers in the same reaction mixture, worms can be genotyped in regard to the mutation on the residue 200 (phenylalanine to tyrosine) of the beta-tubulin which is implicated in BZ resistance. A very high proportion of homozygous SS (Phe/Phe) individuals characterized the BZ susceptible populations, whereas a variable proportion of homozygous rr (Tyr/Tyr) individuals characterized the BZ resistant populations. A positive correlation was observed between the LD50 estimated by egg hatch assay, and the proportion of mutant homozygous individuals rr (Tyr/Tyr). Our PCR method allows the rapid genotyping of numerous worms and permits the detection of the first resistant individuals in a worm population.

  5. Discovery of quinazolin-4-amines bearing benzimidazole fragments as dual inhibitors of c-Met and VEGFR-2. (United States)

    Shi, Lei; Wu, Ting-Ting; Wang, Zhi; Xue, Jia-Yu; Xu, Yun-Gen


    Both c-Met and VEGFR-2 are important targets for the treatment of cancers. In this study, a series of N-(2-phenyl-1H-benzo[d]imidazol-5-yl)quinazolin-4-amine derivatives were designed and identified as dual c-Met and VEGFR-2 inhibitors. Among these compounds bearing quinazoline and benzimidazole fragments, compound 7j exhibited the most potent inhibitory activity against c-Met and VEGFR-2 with IC50 of 0.05μM and 0.02μM, respectively. It also showed the highest anticancer activity against the tested cancer cell lines with IC50 of 1.5μM against MCF-7 and 8.7μM against Hep-G2. Docking simulation supported the initial pharmacophoric hypothesis and suggested a common mode of interaction at the ATP-binding site of c-Met and VEGFR-2, which demonstrates that compound 7j is a potential agent for cancer therapy deserving further researching.

  6. Synthesis and pharmacological evaluation of polyfunctional benzimidazole-NSAID chimeric molecules combining anti-inflammatory, immunomodulatory and antioxidant activities. (United States)

    Bansal, Yogita; Silakari, Om


    Polyfunctional compounds comprise a novel class of therapeutic agents for treatment of multifactorial diseases. The present study reports a series of benzimidazole-non-steroidal anti-inflammatory drugs (NSAIDs) conjugates (1-10) as novel polyfunctional compounds synthesized in the presence of orthophosphoric acid. The compounds were evaluated for anti-inflammatory (carageenan-induced paw edema model), immunomodulatory (direct haemagglutination test and carbon clearance index models), antioxidant (in vitro and in vivo) and for ulcerogenic effects. Each of the compound has retained the anti-inflammatory activity of the corresponding parent NSAID while exhibiting significantly reduced gastric ulcers. Additionally, the compounds are found to possess potent immunostimulatory and antioxidant activities. The compound 8 was maximally potent (antibody titre value 358.4 ± 140.21, carbon clearance index 0.053 ± 0.002 and antioxidant EC50 value 0.03 ± 0.006). These compounds, exhibiting such multiple pharmacological activities, can be taken as lead for the development of potent drugs for the treatment of chronic multifactorial diseases involving inflammation, immune system modulation and oxidative stress such as cancers. The Lipinski's parameters suggested the compounds to be bear drug like properties.

  7. Synthesis of 2-aryl-1,2,4-oxadiazolo-benzimidazoles: Tubulin polymerization inhibitors and apoptosis inducing agents. (United States)

    Kamal, Ahmed; Reddy, T Srinivasa; Vishnuvardhan, M V P S; Nimbarte, Vijaykumar D; Subba Rao, A V; Srinivasulu, Vunnam; Shankaraiah, Nagula


    A new series of 2-aryl 1,2,4-oxadiazolo-benzimidazole conjugates have been synthesized and evaluated for their antiproliferative activity in the sixty cancer cell line panel of the National Cancer Institute (NCI). Compounds 5l (NSC: 761109/1) and 5x (NSC: 761814/1) exhibited remarkable cytotoxic activity against most of the cancer cell lines in the one dose assay and were further screened at five dose concentrations (0.01, 0.1, 1, 10 and 100 μM) which showed GI50 values in the range of 0.79-28.2 μM. Flow cytometric data of these compounds showed increased cells in G2/M phase, which is suggestive of G2/M cell cycle arrest. Further, compounds 5l and 5x showed inhibition of tubulin polymerization and disruption of the formation of microtubules. These compounds induce apoptosis by DNA fragmentation and chromatin condensation as well as by mitochondrial membrane depolarization. In addition, structure activity relationship studies within the series are also discussed. Molecular docking studies of compounds 5l and 5x into the colchicine-binding site of the tubulin, revealed the possible mode of interaction by these compounds.

  8. Synthesis and biological evaluation of new benzimidazole-thiazolidinedione hybrids as potential cytotoxic and apoptosis inducing agents. (United States)

    Sharma, Pankaj; Srinivasa Reddy, T; Thummuri, Dinesh; Senwar, Kishna Ram; Praveen Kumar, Niggula; Naidu, V G M; Bhargava, Suresh K; Shankaraiah, Nagula


    A series of new benzimidazole-thiazolidinedione hybrids has been synthesized and evaluated for their cytotoxic potential against a selected human cancer cell lines of prostate (PC-3 and DU-145), breast (MDA-MB-231), lung (A549) and a normal breast epithelial cells (MCF10A). Among the tested compounds, 11p exhibited promising cytotoxicity with IC50 value of 11.46 ± 1.46 μM on A549 lung cancer cell line and did not show significant toxicity on normal MCF10A cells. Lung cancer cells (A549) have been used to know the mechanism of cell growth inhibition and apoptosis inducing effect with compound 11p. The treatment of A549 cells with 11p showed typical apoptotic morphology like cell shrinkage, chromatin condensation and horseshoe shaped nuclei formation. Flow-cytometry analysis revealed the G2/M phase of cell cycle arrest in a dose dependent manner. Preliminary mechanistic studies suggested that the cell migration was inhibited through the disruption of F-actin protein. Acridine orange-ethidium bromide (AO-EB), DAPI, annexin V-FITC/propidium iodide, rhodamine-123 and MitoSOX assays suggested the induction of apoptosis in A549 cells by compound 11p.

  9. Effect of Mercapto and Methyl Groups on the Efficiency of Imidazole and Benzimidazole-based Inhibitors of Iron Corrosion. (United States)

    Milošev, Ingrid; Kovačević, Nataša; Kokalj, Anton


    We report on the combined experimental and computational study of imidazole- and benzimidazole-based corrosion inhibitors containing methyl and/or mercapto groups. Electrochemical measurements and long-term immersion tests were performed on iron in NaCl solution, whilst computational study explicitly addresses the molecular level details of the bonding on iron surface by means of density functional theory calculations (DFT). Experimental data were the basis for the determination of inhibition efficiency and mechanism. Methyl group combined with mercapto group has a beneficial effect on corrosion inhibition at all inhibitor concentrations. The beneficial effect of mercapto group combined with benzene group is not so pronounced as when combined with methyl group. The latter is in stark contrast with the behaviour found previously on copper, where the effect of methyl group was detrimental and that of mercapto and benzene beneficial. Explicit DFT calculations reveal that methyl-group has a small effect on the inhibitor-surface interaction. In contrast, the presence of mercapto group involves the strong S-surface bonding and consequently the adsorption of inhibitors with mercapto group is found to be more exothermic.

  10. Sulfonated poly(2,5-benzimidazole) (SABPBI) impregnated with phosphoric acid as proton conducting membranes for polymer electrolyte fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Asensio, J.A. [Institut de Ciencia de Materials de Barcelona, Bellaterra (Spain); Universitat Ramon Llull, Barcelona (Spain). Inst. Quimic de Sarria; Borros, S. [Universitat Ramon Llull, Barcelona (Spain). Inst. Quimic de Sarria; Gomez-Romero, P. [Institut de Ciencia de Materials de Barcelona, Bellaterra (Spain)


    Previously cast ABPBI membranes were sulfonated by doping with sulfuric acid followed by heat treatment at 450 {sup o}C for 5 min in air. Sulfonation degrees between 35 and 49% of the benzimidazole rings were achieved. The resulting SABPBI membranes were impregnated with phosphoric acid (H{sub 3}PO{sub 4} 85%/H{sub 2}O, 70:30 bath). For concentrated phosphoric acid baths (above 65%), the capacity of these membranes for phosphoric acid uptake (and consequently also their conductivity) increased with the degree of sulfonation. Sulfonated and acid doped SABPBI membranes were characterized in terms of degree of sulfonation, thermal stability (TGA), X-ray diffraction, FTIR spectroscopy and proton conductivity in the dry state, and compared with phosphoric acid impregnated ABPBI studied earlier. The maximum conductivity measured in dry conditions was 3.5x10{sup -2} S cm{sup -2} at 185 {sup o}C for SABPBI 4.6H{sub 3}PO{sub 4} (with a degree of sulfonation of 41%) which compares favorably with non-sulfonated ABPBI and makes feasible their application in PEM Fuel Cells working at temperatures of 150-200 {sup o}C. (Author)

  11. Synthesis, characterization, biological studies (DNA binding, cleavage, antibacterial and topoisomerase I) and molecular docking of copper(II) benzimidazole complexes. (United States)

    Arjmand, Farukh; Parveen, Shazia; Afzal, Mohd; Shahid, Mohd


    To explore the therapeutic potential of copper-based benzimidazole complexes, tetranuclear Cu(II) complex 1 and dinuclear ternary amino acid complexes 2 and 3 {L-trp and L-val, respectively} were synthesized and thoroughly characterized. In vitro DNA binding studies of complexes 1-3 were carried out employing UV-vis titrations, fluorescence, circular dichroic and viscosity measurements which revealed that the complexes 1-3 bind to CT DNA preferably via groove binding. Complex 1 cleaved pBR322 DNA via hydrolytic pathway (validated by T4 DNA ligase assay), accessible to major groove while 2 followed oxidative mechanism, binding to minor groove of DNA double helix; binding events were further validated by molecular docking studies. Additionally, the complexes 1 and 2 exhibit high Topo-I inhibitory activity at different concentrations. The complexes 1-3 were evaluated for antibacterial activity against Escherichia coli and Staphylococcus aureus, and 2 was found to be most effective against Gram-positive bacteria.

  12. Pharmacophore modeling and 3D-QSAR studies on substituted benzothiazole / benzimidazole analogues as DHFR inhibitors with antimycobacterial activity

    Directory of Open Access Journals (Sweden)

    R. Priyadarsini


    Full Text Available The resurgence of tuberculosis and the emergence of multidrug-resistant strains of Mycobacteria drugs has propelled the development of new structural classes of antitubercular agents. The present study was undertaken to investigate the opportunities which the enzyme dihydrofolate reductase, a promising drug target for treatmentof Mycobacterial infections offers for the development of new TB drugs. Pharmacophore models were established by using the HipHop and HypoGen algorithms implemented in the Catalyst software package. Thebest quantitative pharmacophore model, consisted of two hydrogen bond acceptor, a hydrophobic aliphatic, and a ring aromatic feature which has the highest correlation coefficient (0.93, as well as enrichment factor of 1.75 and Goodness of hit score of 0.73. Based on the pharmacophore model some leads were optimized and some of its derivatives were synthesized and analysed by following QSAR studies. About 25 compounds of substituted benzothiazole/ benzimidazole derivatives were synthesized as potent DHFR inhibitors and screened for antimycobacterial activity. To further explore the structure-activity relationships of all newly synthesized compounds, 3D-QSAR analyses were developed. MFA studies were performed with the QSAR module of Cerius2 using genetic partial least squares (G/PLS algorithm. The predictive ability of the developed model was assessed using a training set of 25 and a test set of 5 compounds (r2pred = 0.924.The analyzed MF

  13. Synthesis, electronic structure and spectral fluorescent properties of vinylogous merocyanines derived from 1,3-dialkyl-benzimidazole and malononitrile (United States)

    Kulinich, Andrii V.; Mikitenko, Elena K.; Ishchenko, Alexander A.


    A vinylogous series of merocyanines were synthesized with 1,3-dibutyl-benzimidazole and malononitrile residues as the donor and acceptor terminal groups. These dyes do not comprise carbonyl groups, which are prone to the strong specific solvation by polar solvents up to hydrogen bond formation, and nevertheless they possess distinct reversed solvatochromism, i.e. their molecules have very high dipolarity. At that, they are soluble in a wide range of solvents from n-hexane to ethanol and do not aggregate readily. They were studied thoroughly by UV/Vis, fluorescence, IR, and NMR spectroscopy methods. Their structure and spectral properties in the ground and excited fluorescent states were modelled at the DFT level both in vacuum and in solvents of various polarities by using the PCM solvent field simulation. The calculations were performed using several hybrid functionals (B3LYP, CAM-B3LYP, and wB97XD) and the split-valence 6-31G (d,p) basis set.

  14. Metal coordination polymers of 2,3-bis(benzimidazol-1-ylmethyl)quinoxaline: Syntheses, crystal structures and luminescent properties (United States)

    Du, Jian-Long; Wei, Zi-Zhang; Hu, Tong-Liang


    Two new metal-organic frameworks, {[Cu LI]·CHCl 3} ∞( 1) and {[Hg L(Br) 2] 4·2CH 2Cl 2} ∞ ( 2) have been prepared by reacting CuI and HgBr 2 with the new flexible ligand L [ L = 2,3-Bis(benzimidazol-1-ylmethyl)quinoxaline]. Both complexes have been characterized by elemental analysis, IR, TGA, XRPD, and single crystal X-ray diffraction determination. In 1, the Cu(I) ion takes tetrahedral coordination geometry, and the flexible ligands bridge dinuclear units (Cu 2I 2) to form a one dimensional (1D) double chain structure. While in 2, the Hg(II) coordinates to two bromine ions and two nitrogen donors of L to form a 1D coordination polymer. The structure differences of the two complexes mainly depend on the geometry of the metal ions and the influence of anions. The coordination features of the ligand have also been primarily investigated by density functional theory (DFT) calculations. In addition, the fluorescent properties of the complexes and free ligand L have been investigated in the solid state at room temperature.

  15. Computational Study Exploring the Interaction Mechanism of Benzimidazole Derivatives as Potent Cattle Bovine Viral Diarrhea Virus Inhibitors. (United States)

    Wang, Jinghui; Yang, Yinfeng; Li, Yan; Wang, Yonghua


    Bovine viral diarrhea virus (BVDV) infections are prevailing in cattle populations on a worldwide scale. The BVDV RNA-dependent RNA polymerase (RdRp), as a promising target for new anti-BVDV drug development, has attracted increasing attention. To explore the interaction mechanism of 65 benzimidazole scaffold-based derivatives as BVDV inhibitors, presently, a computational study was performed based on a combination of 3D-QSAR, molecular docking, and molecular dynamics (MD) simulations. The resultant optimum CoMFA and CoMSIA models present proper reliabilities and strong predictive abilities (with Q(2) = 0. 64, R(2)ncv = 0.93, R(2)pred = 0.80 and Q(2) = 0. 65, R(2)ncv = 0.98, R(2)pred = 0.86, respectively). In addition, there was good concordance between these models, molecular docking, and MD results. Moreover, the MM-PBSA energy analysis reveals that the major driving force for ligand binding is the polar solvation contribution term. Hopefully, these models and the obtained findings could offer better understanding of the interaction mechanism of BVDV inhibitors as well as benefit the new discovery of more potent BVDV inhibitors.

  16. Novel Benzothiazole, Benzimidazole and Benzoxazole Derivatives as Potential Antitumor Agents: Synthesis and Preliminary in Vitro Biological Evaluation

    Directory of Open Access Journals (Sweden)

    Li Yang


    Full Text Available In a previous hit-to-lead research program targeting anticancer agents, two promising lead compounds, 1a and 1b, were found. However, the poor solubility of 1a and 1b made difficult further in vivo studies. To solve this problem, a lead optimization was conducted through introducing N-methyl-piperazine groups at the 2-position and 6-position. To our delight, the optimized analogue 1d showed comparable antiproliferative activity in vitro with better solubility, compared with 1a. Based on this result, the replacement of the benzothiazole scaffold with benzimidazole and benzoxazole moieties afforded 1f and 1g, whose activities were fundamentally retained. In the preliminary in vitro biological evaluation, the immunofluorescence staining of HCT116 cells indicated that 1d, 1f and 1g led to cytosolic vacuolization which was not induced by 1a at low micromolecular concentrations. These results suggest that these optimized compounds might potentially constitute a novel class of anticancer agents, which merit further studies.

  17. Novel benzothiazole, benzimidazole and benzoxazole derivatives as potential antitumor agents: synthesis and preliminary in vitro biological evaluation. (United States)

    Xiang, Pu; Zhou, Tian; Wang, Liang; Sun, Chang-Yan; Hu, Jing; Zhao, Ying-Lan; Yang, Li


    In a previous hit-to-lead research program targeting anticancer agents, two promising lead compounds, 1a and 1b, were found. However, the poor solubility of 1a and 1b made difficult further in vivo studies. To solve this problem, a lead optimization was conducted through introducing N-methyl-piperazine groups at the 2-position and 6-position. To our delight, the optimized analogue 1d showed comparable antiproliferative activity in vitro with better solubility, compared with 1a. Based on this result, the replacement of the benzothiazole scaffold with benzimidazole and benzoxazole moieties afforded 1f and 1g, whose activities were fundamentally retained. In the preliminary in vitro biological evaluation, the immunofluorescence staining of HCT116 cells indicated that 1d, 1f and 1g led to cytosolic vacuolization which was not induced by 1a at low micromolecular concentrations. These results suggest that these optimized compounds might potentially constitute a novel class of anticancer agents, which merit further studies.

  18. Derivatives containing both coumarin and benzimidazole potently induce caspase-dependent apoptosis of cancer cells through inhibition of PI3K-AKT-mTOR signaling. (United States)

    Liu, Haitao; Wang, Yubin; Sharma, Ashok; Mao, Rui; Jiang, Na; Dun, Boying; She, Jin-Xiong


    Coumarins are a large family of compounds derived from a wide range of plants, fungi, and bacteria, and coumarin derivatives can have extremely variable structures and consequently diverse biological properties including antitumor activity. Compounds that bear a benzimidazole moiety are known to possess antitumor activity and a variety of other biological activities. High-throughput screening of a compound library identified a coumarin-containing and a benzimidazole-containing compound [#32, 7-(diethylamino)-3-(1-methyl-1H-benzimidazol-2-yl)-2H-chromen-2-one] that has potent anticancer activity. Evaluation of 17 additional analogs further identified three compounds with anticancer activity in 14 different human cancer cell lines. Fluorescence-activated cell sorting and western blotting analyses suggested that these compounds can induce caspase-dependent apoptosis. Real-time reverse transcriptase PCR analyses of 26 cancer-related genes revealed that seven genes (NPPB, ATF3, DDIT4, CDH10, TSPAN14, TXNIP, and AXL) were significantly upregulated and nine genes (PAGE4, LRP8, SNCAIP, IGFBP5, SLCO2A1, CLDN2, ESRRG, D2HGDH, and PDGFRA) were significantly downregulated. The most upregulated gene is natriuretic peptide precursor B (NPPB) or brain natriuretic peptide, which is increased by 7-, 27-, and 197-fold at 12, 24, and 48 h, respectively. The second most upregulated gene is ATF3, which is increased by 23-fold at the 48 h timepoint. PAGE4 and IGFBP5 are the two most downregulated genes, with a 17-fold reduction in both genes. The expression of several genes (DDIT4, PDGFRA, LRP8, IGFBP5) and western blotting data on key signaling proteins indicate that compound #32 significantly inhibits the PI3K-AKT-mTOR pathway, an intracellular signaling pathway critical in cell proliferation and apoptosis.

  19. Hepatic microsomal metabolism of the anthelmintic benzimidazole fenbendazole: enhanced inhibition of cytochrome P450 reactions by oxidized metabolites of the drug. (United States)

    Murray, M; Hudson, A M; Yassa, V


    Potentiation of the anthelmintic action of benzimidazole carbamates, such as fenbendazole [methyl 5(6)-(phenylthio)-1H-benzimidazol-2-ylcarbamate], has been noted during concurrent administration of benzimidazoles that possess no intrinsic anthelmintic activity. This study investigated the possibility that inhibition of P450 enzymes by fenbendazole and its metabolites could play a role in the potentiation phenomenon. Fenbendazole underwent P450-mediated oxidation in microsomes from untreated rat liver to the sulfoxide and (4'-hydroxyphenyl)thio metabolites [2.92 and 2.87 nmol/(mg of protein.h)]. Pretreatment of rats with phenobarbital or dexamethasone enhanced sulfoxidation by 1.9- and 2.9-fold, respectively. 4'-Hydroxylation was increased slightly (by 28%) by phenobarbital and decreased slightly (by 41%) by dexamethasone. Induction also promoted further metabolism of the sulfoxide to fenbendazole sulfone. Immunoinhibition and chemical inhibition studies suggested that P450 3A proteins and the flavin-containing monooxygenase are involved in sulfoxide and sulfone formation whereas 4'-hydroxylation involved the P450s 2C11, 2C6, and 2B1, depending on the type of induction. In untreated rat liver, the sulfoxide and (4'-hydroxyphenyl)thio metabolites of fenbendazole were relatively potent inhibitors of P450-mediated androstenedione 16 alpha-, 16 beta-, and 6 beta-hydroxylation (IC50 values of 42, 36, and 74 microM, respectively); 7 alpha-hydroxylase activity was uninhibited. In contrast, fenbendazole and its sulfone metabolite were not inhibitors of these reactions. Mixed-function oxidase activities in phenobarbital-induced rat hepatic microsomes were refractory to inhibition by most compounds, but P450 1A1 mediated activities in microsomes from beta-naphthoflavone-induced rat liver were quite susceptible to inhibition by fenbendazole sulfoxide. Studies with two analogous sulfoxides yielded similar findings.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Development and validation of an ultra high performance liquid chromatography tandem mass spectrometry method for simultaneous determination of sulfonamides, quinolones and benzimidazoles in bovine milk. (United States)

    Hou, Xiao-Lin; Chen, Guo; Zhu, Li; Yang, Ting; Zhao, Jian; Wang, Lei; Wu, Yin-Liang


    A simple, sensitive and reliable analytical method was developed for the simultaneous determination of 38 veterinary drugs (18 sulfonamides, 11 quinolones and 9 benzimidazoles) and 8 metabolites of benzimidazoles in bovine milk by ultra high performance liquid chromatography-positive electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). Samples were extracted with acidified acetonitrile, cleaned up with Oasis(®) MCX cartridges, and analyzed by LC-MS/MS on an Acquity UPLC(®) BEH C18 column with gradient elution. The method allows such multi-analyte measurements within a 13min runtime while the specificity is ensured through the MRM acquisition mode. The method was validated according to the European Commission Decision 2002/657/EC determining specificity, decision limit (CCα), detection capability (CCβ), recovery, precision, linearity and stability. For compounds which have MRLs in bovine milk, the CCα values fall into a range from 11 to 115μg/kg, and the CCβ values fall within a range of 12-125μg/kg. For compounds which have not MRLs in bovine milk, the CCα values fall into a range from 0.01 to 0.08μg/kg, and the CCβ values fall within a range of 0.02-0.11μg/kg. The mean recoveries of the 46 analytes were between 87 and 119%. The calculated RSD values of repeatability and within-laboratory reproducibility experiments were below 11% and 15% for the 46 compounds, respectively. The method was demonstrated to be suitable for the simultaneous determination of sulfonamides, quinolones and benzimidazoles in bovine milk.

  1. Critical tests in equids with fenbendazole alone or combined with piperazine: particular reference to activity on benzimidazole-resistant small strongyles. (United States)

    Lyons, E T; Tolliver, S C; Drudge, J H


    Seven critical tests in equids were conducted with single doses of fenbendazole (5 mg kg-1) alone (Panacur--American Hoechst, Somerville, NJ); (2 tests with paste and 1 with suspension formulation) or in combination with piperazine (American Hoechst); (40 mg base kg-1); (4 tests with paste formulation). The main purpose of the tests was evaluation of activity against benzimidazole-resistant small strongyles (Cyathostomum catinatum, Cyathostomum coronatum, Cylicocyclus nassatus, Cylicostephanus goldi, and Cylicostephanus longibursatus). Natural infections of 2 populations of benzimidazole-resistant small strongyles were evaluated; 1 was population B in 2 horses and the other was population S in 5 ponies. Removal of the 5 species of population B was 49-91% in the animal treated with fenbendazole paste alone and 100% (4 of these species present) in the animal treated with the combination. For population S, 2 of the 5 resistant species were present in small numbers in 1 animal treated with fenbendazole paste alone and all were removed; the 1 animal receiving fenbendazole suspension alone had removals of 0-70% for the 5 benzimidazole-resistant species. Also for population S, the 5 resistant species were present in 2 animals treated with the paste combination and removal was 98-100% and of 4 of the 5 resistant species in 1 animal, removal was 76-99%. Removal of large strongyles (Strongylus vulgaris and Strongylus edentatus) was 92-100% for fenbendazole paste alone or in combination with piperazine in the 5 infected animals. For Oxyuris equi, present in 1 animal treated with the combination, there was 91% removal of immature and 100% removal of mature specimens. There probHably was no activity by fenbendazole alone or the combination against bots, tapeworms, and parenteral stages of S. vulgaris and S. edentatus. The combination may have had some activity against immature Habronema spp. and mature abronema muscae.

  2. Highly potent extranuclear-targeted luminescent iridium(iii) antitumor agents containing benzimidazole-based ligands with a handle for functionalization. (United States)

    Yellol, Jyoti; Pérez, Sergio A; Yellol, Gorakh; Zajac, Juraj; Donaire, Antonio; Vigueras, Gloria; Novohradsky, Vojtech; Janiak, Christoph; Brabec, Viktor; Ruiz, José


    A series of 6 substitutionally inert and luminescent iridium(iii) antitumor agents of the type [Ir(C(∧)N)2(N(∧)N)][PF6] containing a benzimidazole N(∧)N ligand with an ester group as a handle for further functionalization has been prepared. They exhibit IC50 values in the high nanomolar range in some ovarian and breast cancer cell lines (approximately 100× more cytotoxic than cisplatin (CDDP) in MDA-MB-231) and are located in the actin cortex predominantly as shown by confocal luminescence microscopy. This discovery could open the door to a new large family of drug bioconjugates with diverse and simultaneous functions.

  3. Discovery of benzimidazole-diamide finger loop (Thumb Pocket I) allosteric inhibitors of HCV NS5B polymerase: Implementing parallel synthesis for rapid linker optimization. (United States)

    Goulet, Sylvie; Poupart, Marc-André; Gillard, James; Poirier, Martin; Kukolj, George; Beaulieu, Pierre L


    Previously described SAR of benzimidazole-based non-nucleoside finger loop (Thumb Pocket I) inhibitors of HCV NS5B polymerase was expanded. Prospecting studies using parallel synthesis techniques allowed the rapid identification of novel cinnamic acid right-hand sides that provide renewed opportunities for further optimization of these inhibitors. Novel diamide derivatives such as 44 exhibited comparable potency (enzymatic and cell-based HCV replicon) as previously described tryptophan-based inhibitors but physicochemical properties (e.g., aqueous solubility and lipophilicity) have been improved, resulting in molecules with reduced off-target liabilities (CYP inhibition) and increased metabolic stability.

  4. Iodido[5-methyl-1H-benzimidazole-2(3H-thione-κS]bis(triphenylphosphane-κPcopper(I methanol monosolvate

    Directory of Open Access Journals (Sweden)

    Yu-Han Jiang


    Full Text Available In the title compound, [CuI(C8H8N2S(C18H15P2]·CH3OH, the coordination environment around the CuI atom is distorted tetrahedral, defined by two P atoms of two triphenylphosphane ligands, one S atom of a 5-methyl-1H-benzimidazole-2(3H-thione ligand and one I atom. The complex molecules and the methanol solvent molecules are connected via N—H...O and O—H...I hydrogen bonds, forming a chain along [010]. An intramolecular N—H...I hydrogen bond is also observed.

  5. Tetra-μ3-iodido-tetrakis{[ethyl 2-(1H-benzimidazol-1-ylacetate-κN3]copper(I}

    Directory of Open Access Journals (Sweden)

    Lili Yang


    Full Text Available The complex molecule of the tetranuclear cubane-type title compound, [Cu4I4(C11H12N2O24], has crystallographically imposed fourfold inversion symmetry. The CuI ions are coordinated in a distorted tetrahedral geometry by an N atom of a benzimidazole ring system and three μ3-iodide ions, forming a Cu4I4 core. In the crystal, complex molecules are connected into a three-dimensional network by C—H...O hydrogen bonds involving H and O atoms of adjacent ethoxycarbonyl groups.

  6. Anion-controlled assembly of metal 3,5-bis(benzimidazol-1-ylmethyl) benzoate complexes: Synthesis, characterization and property

    Energy Technology Data Exchange (ETDEWEB)

    Kuai, Hai-Wei [Coordination Chemistry Institute, State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing National Laboratory of Microstructures, Nanjing University, Nanjing 210093 (China); Faculty of Life Science and Chemical Engineering, Huaiyin Institute of Technology, Huaian 223003 (China); Lv, Gao-Chao; Hou, Chao [Coordination Chemistry Institute, State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing National Laboratory of Microstructures, Nanjing University, Nanjing 210093 (China); Sun, Wei-Yin, E-mail: [Coordination Chemistry Institute, State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing National Laboratory of Microstructures, Nanjing University, Nanjing 210093 (China)


    Hydrothermal reactions of 3,5-bis(benzimidazol-1-ylmethyl)benzoic acid (HL) with Cd(II), Cu(II) and Zn(II) salts provide eight new metal complexes which were characterized by single crystal and powder X-ray diffraction, IR, elemental and thermogravimetric analyses. Two cadmium frameworks [Cd(L){sub 2}]·2H{sub 2}O (1) and [Cd(L)Cl] (2) have 3D structures with (4{sup 2}.6{sup 5}.8{sup 3})(4{sup 2}.6) and rtl (4.6{sup 2}){sub 2}(4{sup 2}.6{sup 10}.8{sup 3}) topologies, respectively. Structural diversity of four copper complexes [Cu{sub 3}(L){sub 2}]·NO{sub 3}·0.5H{sub 2}O (3), [Cu{sub 2}(HL){sub 2}(SO{sub 4})]·3.5H{sub 2}O (4), [Cu(L)(bdc){sub 0.5}]·1.5H{sub 2}O (5) and [Cu{sub 2}(L)(HL)(Hbdc)] (6) (H{sub 2}bdc=1,4-benzenedicarboxylic acid) is achieved through the alteration of copper salts and addition of auxiliary ligand. As a result, 3 has a 1D ladder structure, 4 is a discrete dinuclear complex, 5 displays a (3,4)-connected 2-nodal 3-fold interpenetrating framework with (4{sup 2}.6.10{sup 2}.12)(4{sup 2}.6) topology, 6 exhibits a 4-connected uninodal 2D sql (4{sup 4}.6{sup 2}) network. Within the zinc series, ZnCl{sub 2} and ZnSO{sub 4} were used for the syntheses of [Zn(L)Cl] (7) and [Zn(L)(SO{sub 4}){sub 0.5}]·2H{sub 2}O (8), respectively. 7 shows a 3-connected uninodal 2D hcb network with (6{sup 3}) topology and 8 is a (3,6)-connected 2-nodal 3D framework with (4{sup 2}.6){sub 2}(4{sup 4}.6{sup 2}.8{sup 8}.10) topology. The luminescent properties of the Cd(II) and Zn(II) complexes were investigated. - Graphical abstract: Eight new complexes have been successfully synthesized from the hydrothermal reactions of Cd(II), Cu(II) and Zn(II) salts with 3,5-bis(benzimidazol-1-ylmethyl)benzoic acid. The complexes exhibited anion-controlled structural diversity. - Highlights: • Metal complexes have diverse structures of 1D chains, 2D networks and 3D frameworks. • Anion-controlled assembly of the complexes is reported. • The luminescent properties of the Cd

  7. Six complexes based on bis(imidazole/benzimidazole-1-yl)pyridazine ligands: Syntheses, structures and properties (United States)

    Wang, Xin-Fang; Du, Ceng-Ceng; Zhou, Sheng-Bin; Wang, Duo-Zhi


    Herein we reported six new Ni(II)/Cu(II)/Zn(II) complexes, namely, [Ni(L1)4(OH)2] (1), [Cu(L1)4(OH)2] (2), [Cu(L1)2(SiF6)]n (3), {[Cu(L2)(HCOO)2]·H2O·CH3OH}n (4), [Ni(L2)2(NO3)2]n (5) and {[Zn(L2)Cl2]·DMF}n (6) (L1 = 3,6-bis(imidazole-1-yl)pyridazine, L2 = 3,6-bis(benzimidazole-1-yl)pyridazine), which were characterized by single-crystal X-ray diffraction, elemental analysis, IR, PXRD. These complexes have been successfully constructed under interface diffusion process, heating reflux or hydrothermal conditions. The structures of 1 and 2 are mononuclear complexes. Complex 3 exhibits a 6-connected 3D topology network with the Schläfli symbol of (412·63). In complex 4, two Cu(II) were connected through two HCOO- anions to form dinuclear structure unit, which is arranged into a 1D ladder-like structure by μ2-L2 ligands. Complexes 5 and 6 are 1D zigzag chains connected by L2 ligands, but the Ni(II) ion is six-coordinated in 5 and the Zn(II) ion is four-coordinated in 6. Moreover, the solid-state luminescence property and UV-vis diffuse reflection spectrum of complex 6 have been investigated and discussed.

  8. The influence of cryopreservation on a benzimidazole-resistant isolate of Haemonchus contortus conditioned for inhibited development. (United States)

    Hendrikx, W M; Boersema, J H; Eysker, M


    Larvae of a fenbendazole (FBZ)-selected, benzimidazole-resistant strain of Haemonchus contortus were conditioned for inhibited development during 7 weeks at 15 degrees C. Sheep raised nearly worm-free were infected with nonfrozen larvae (L3). Larvae from the same batch were exsheathed and cryopreserved over liquid nitrogen for 1 year, and another group of sheep was infected with the same dose of these L3 larvae after thawing. Egg hatch assays for all sheep were done between 21 and 30 days post infection (p.i.). Fenbendazole susceptibility was tested by treating 50% of each group of sheep on day 30 p.i. Worm counts of all sheep were done on day 38 p.i. The exsheathment time of the designated frozen L3 larvae at 15 degrees C exceeded the usual time span at room temperature. Of the frozen L3 larvae, 60% was motile after thawing. The mean LC50 values (micrograms tiabendazole/ml) and the mean percentage of efficacy after FBZ treatment against total worm burden, adults and early L4 larvae of nonfrozen and frozen H. contortus were not significantly different. The mean percentages of take (infectivity) for nonfrozen and frozen doses were 35.3% and 5.9%, respectively (P less than 0.001). In nontreated sheep, the mean percentages of inhibition for nonfrozen and frozen doses were 91.9%, and 54.2%, respectively (P less than 0.01). The exsheathment time seems to be temperature-dependent. The induction of inhibited development of L3 larvae during 7 weeks was as effective as during 5 weeks at 15 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Phylogenetic Characterization of β-Tubulins and Development of Pyrosequencing Assays for Benzimidazole Resistance in Cattle Nematodes (United States)

    Demeler, Janina; Krüger, Nina; Krücken, Jürgen; von der Heyden, Vera C.; Ramünke, Sabrina; Küttler, Ursula; Miltsch, Sandra; López Cepeda, Michael; Knox, Malcolm; Vercruysse, Jozef; Geldhof, Peter; Harder, Achim; von Samson-Himmelstjerna, Georg


    Control of helminth infections is a major task in livestock production to prevent health constraints and economic losses. However, resistance to established anthelmintic substances already impedes effective anthelmintic treatment in many regions worldwide. Thus, there is an obvious need for sensitive and reliable methods to assess the resistance status of at least the most important nematode populations. Several single nucleotide polymorphisms (SNPs) in the β-tubulin isotype 1 gene of various nematodes correlate with resistance to benzimidazoles (BZ), a major anthelmintic class. Here we describe the full-length β-tubulin isotype 1 and 2 and α-tubulin coding sequences of the cattle nematode Ostertagia ostertagi. Additionally, the Cooperia oncophora α-tubulin coding sequence was identified. Phylogenetic maximum-likelihood analysis revealed that both isotype 1 and 2 are orthologs to the Caenorhabditis elegans ben-1 gene which is also associated with BZ resistance upon mutation. In contrast, a Trichuris trichiura cDNA, postulated to be β-tubulin isotype 1 involved in BZ resistance in this human parasite, turned out to be closely related to C. elegans β-tubulins tbb-4 and mec-7 and would therefore represent the first non-ben-1-like β-tubulin to be under selection through treatment with BZs. A pyrosequencing assay was established to detect BZ resistance associated SNPs in β-tubulin isotype 1 codons 167, 198 and 200 of C. oncophora and O. ostertagi. PCR-fragments representing either of the two alleles were combined in defined ratios to evaluate the pyrosequencing assay. The correlation between the given and the measured allele frequencies of the respective SNPs was very high. Subsequently laboratory isolates and field populations with known resistance status were analyzed. With the exception of codon 167 in Cooperia, increases of resistance associated alleles were detected for all codons in at least one of the phenotypically resistant population. Pyrosequencing

  10. Multiplex PCR Detection of Alleles Responsible for Benzimidazole-Susceptibility or-Resistance in Natural Populations of Haemonchus contortus

    Institute of Scientific and Technical Information of China (English)

    BO Xin-wen; LI Xiang-rui


    A multiplex PCR was developed to detect benzimidazole-resistance (BZ-R) or -susceptibility (BZ-S) in Haemonchus contortus by amplification with 4 primers of a sequence of the GRU-1 gene of β-tubulin of H. contortus making use of sequence information available in Genbank. The method was based on two allele-non-specific primers and two allelespecific primers. Fl (264 bp) and F3 (799 bp) should be produced in BZ-R, F2 (585 bp) and F3 in BZ-S. With this method,we demonstrated that H. contortus BZ-R strain from Australia showed Fl and F3, and the worm BZ-S strain from Shanghai did F2 and F3. Sequence analysis of the isotype 1 gene of β-tubulin of BZ-R from Australia and BZ-S from Shanghai showed the code in residue 200 of the gene was respectively TAC and TTC. The LD50 of albendazole of the Australian BZR strain was 0.54 μg mL-1, the Shanghai BZ-S strain was only 0.0023 μg mL-1 by EHA (egg hatch assay). The multiplex PCR could determinate the genotype of single adult worm or several third stage larvae and was performed on at least 50 ng of genomic DNA. BZ-R H. contortus were not detected in Shihezi and Yining of the Xinjiang, Wuhe of the Anhui Province,Nanjing and Xuzhou of the Jiangsu Province. The LD50 of the H. contortus from these locations to albendazole as determined by EHA varied between 0.0023-0.0032 μg mL-1. The result indicated that the multiplex PCR could be used to differentiate BZ-R and BZ-S of H. contortus and that the BZ-R situation of H. contortus was not serious in China.

  11. Identification of Benzimidazole Diamides as Selective Inhibitors of the Nucleotide-Binding Oligomerization Domain 2 (NOD2) Signaling Pathway (United States)

    Rickard, David J.; Sehon, Clark A.; Kasparcova, Viera; Kallal, Lorena A.; Zeng, Xin; Montoute, Monica N.; Chordia, Tushar; Poore, Derek D.; Li, Hu; Wu, Zining; Eidam, Patrick M.; Haile, Pamela A.; Yu, Jong; Emery, John G.; Marquis, Robert W.; Gough, Peter J.; Bertin, John


    NOD2 is an intracellular pattern recognition receptor that assembles with receptor-interacting protein (RIP)-2 kinase in response to the presence of bacterial muramyl dipeptide (MDP) in the host cell cytoplasm, thereby inducing signals leading to the production of pro-inflammatory cytokines. The dysregulation of NOD2 signaling has been associated with various inflammatory disorders suggesting that small-molecule inhibitors of this signaling complex may have therapeutic utility. To identify inhibitors of the NOD2 signaling pathway, we utilized a cell-based screening approach and identified a benzimidazole diamide compound designated GSK669 that selectively inhibited an MDP-stimulated, NOD2-mediated IL-8 response without directly inhibiting RIP2 kinase activity. Moreover, GSK669 failed to inhibit cytokine production in response to the activation of Toll-like receptor (TLR)-2, tumor necrosis factor receptor (TNFR)-1 and closely related NOD1, all of which share common downstream components with the NOD2 signaling pathway. While the inhibitors blocked MDP-induced NOD2 responses, they failed to block signaling induced by NOD2 over-expression or single stranded RNA, suggesting specificity for the MDP-induced signaling complex and activator-dependent differences in NOD2 signaling. Investigation of structure-activity relationship allowed the identification of more potent analogs that maintained NOD2 selectivity. The largest boost in activity was achieved by N-methylation of the C2-ethyl amide group. These findings demonstrate that the NOD2 signaling pathway is amenable to modulation by small molecules that do not target RIP2 kinase activity. The compounds we identified should prove useful tools to investigate the importance of NOD2 in various inflammatory processes and may have potential clinical utility. PMID:23936340

  12. Identification of benzimidazole diamides as selective inhibitors of the nucleotide-binding oligomerization domain 2 (NOD2 signaling pathway.

    Directory of Open Access Journals (Sweden)

    David J Rickard

    Full Text Available NOD2 is an intracellular pattern recognition receptor that assembles with receptor-interacting protein (RIP-2 kinase in response to the presence of bacterial muramyl dipeptide (MDP in the host cell cytoplasm, thereby inducing signals leading to the production of pro-inflammatory cytokines. The dysregulation of NOD2 signaling has been associated with various inflammatory disorders suggesting that small-molecule inhibitors of this signaling complex may have therapeutic utility. To identify inhibitors of the NOD2 signaling pathway, we utilized a cell-based screening approach and identified a benzimidazole diamide compound designated GSK669 that selectively inhibited an MDP-stimulated, NOD2-mediated IL-8 response without directly inhibiting RIP2 kinase activity. Moreover, GSK669 failed to inhibit cytokine production in response to the activation of Toll-like receptor (TLR-2, tumor necrosis factor receptor (TNFR-1 and closely related NOD1, all of which share common downstream components with the NOD2 signaling pathway. While the inhibitors blocked MDP-induced NOD2 responses, they failed to block signaling induced by NOD2 over-expression or single stranded RNA, suggesting specificity for the MDP-induced signaling complex and activator-dependent differences in NOD2 signaling. Investigation of structure-activity relationship allowed the identification of more potent analogs that maintained NOD2 selectivity. The largest boost in activity was achieved by N-methylation of the C2-ethyl amide group. These findings demonstrate that the NOD2 signaling pathway is amenable to modulation by small molecules that do not target RIP2 kinase activity. The compounds we identified should prove useful tools to investigate the importance of NOD2 in various inflammatory processes and may have potential clinical utility.

  13. Unusually strong binding to the DNA minor groove by a highly twisted benzimidazole diphenylether: induced fit and bound water. (United States)

    Tanious, Farial A; Laine, William; Peixoto, Paul; Bailly, Christian; Goodwin, Kristie D; Lewis, Mark A; Long, Eric C; Georgiadis, Millie M; Tidwell, Richard R; Wilson, W David


    RT29 is a dicationic diamidine derivative that does not obey the classical "rules" for shape and functional group placement that are expected to result in strong binding and specific recognition of the DNA minor groove. The compound contains a benzimidazole diphenyl ether core that is flanked by the amidine cations. The diphenyl ether is highly twisted and gives the entire compound too much curvature to fit well to the shape of the minor groove. DNase I footprinting, fluorescence intercalator displacement studies, and circular dichroism spectra, however, indicate that the compound is an AT specific minor groove binding agent. Even more surprisingly, quantitative biosensor-surface plasmon resonance and isothermal titration calorimetric results indicate that the compound binds with exceptional strength to certain AT sequences in DNA with a large negative enthalpy of binding. Crystallographic results for the DNA complex of RT29 compared to calculated results for the free compound show that the compound undergoes significant conformational changes to enhance its minor groove interactions. In addition, a water molecule is incorporated directly into the complex to complete the compound-DNA interface, and it forms an essential link between the compound and base pair edges at the floor of the minor groove. The calculated DeltaCp value for complex formation is substantially less than the experimentally observed value, which supports the idea of water being an intrinsic part of the complex with a major contribution to the DeltaCp value. Both the induced fit conformational changes of the compound and the bound water are essential for strong binding to DNA by RT29.


    Directory of Open Access Journals (Sweden)

    Demet Gürbüz


    Full Text Available 5,6-Dichloro/dimethyl-2-(2´,3´/2´,4´/2´,5´/3´,4´/3´,5´-dimethoxyphenyl-1H-benzimidazoles were synthesized and characterized by using analytical data, FT-IR, FT-Raman, NMR, ESI-MS and fl uorescence spectroscopy. The optimized molecular geometry, zero point energy, dipole moment, ESE, band gap and charge distributions were calculated by Gaussian 09 using Density Functional Theory (DFT, RB3LYP with 6-31++G(d,p basis set. According to the calculations, the molecules have structures with various torsion angles between the benzimidazole and benzene rings from 9.7º to 47.8º. The calculated energy values with ZPE correction and DFT show that the methyl derivatives are more stable than the chloro forms. 3´,4´-Dimethoxy derivatives have higher decomposition points in comparison with the other compounds in series. The chlorine atoms of 5,6-dichloro-2- (2´,3´/2´,4´/2´,5´/3´,4´/3´,5´-dimethoxyphenyl-1H-benzimidazoles are positively charged whereas the C5 and C6 carbon atoms are negatively charged due to the attached chlorine atoms, in virtue of the electron withdrawing characteristic of the imidazole part of the benzimidazole ring. Also, some calculated prominent bond lengths and bond angles were discussed.

  15. Simultaneous determination of nitroimidazoles, benzimidazoles, and chloramphenicol components in bovine milk by ultra-high performance liquid chromatography-tandem mass spectrometry. (United States)

    Wang, Yuanyuan; Li, Xiaowei; Zhang, Zhiwen; Ding, Shuangyang; Jiang, Haiyang; Li, Jiancheng; Shen, Jianzhong; Xia, Xi


    A sensitive, confirmatory ultra-high performance liquid chromatography-tandem mass spectrometric method was developed and validated to detect 23 veterinary drugs and metabolites (nitroimidazoles, benzimidazoles, and chloramphenicol components) in bovine milk. Compounds of interest were sequentially extracted from milk with acetonitrile and basified acetonitrile using sodium chloride to induce liquid-liquid partition. The extract was purified on a mixed mode solid-phase extraction cartridge. Using rapid polarity switching in electrospray ionization, a single injection was capable of detecting both positively and negatively charged analytes in a 9 min chromatography run time. Recoveries based on matrix-matched calibrations and isotope labeled internal standards for milk ranged from 51.7% to 101.8%. The detection limits and quantitation limits of the analytical method were found to be within the range of 2-20 ng/kg and 5-50 ng/kg, respectively. The recommended method is simple, specific, and reliable for the routine monitoring of nitroimidazoles, benzimidazoles, and chloramphenicol components in bovine milk samples.

  16. Co(II), Ni(II) and Cu(II) complexes of methyl-5-(Phenylthio) benzimidazole-2-carbamate: Molecular structures, spectral and DFT calculations (United States)

    Mansour, Ahmed M.; El Bakry, Eslam M.; Abdel-Ghani, Nour T.


    [Co(FBZ)2(H2O)]·2NO3·0.5H2O (1), [Ni(FBZ)2X2]·zH2O (X = Cl​-, z = 0.5 (2) and X = CH3COO-, z = 1 (3)) and [Cu(FBZ)2(H2O) (NO3)]·NO3·1.5H2O (4) (FBZ = methyl-5-(Phenylthio) benzimidazole-2-carbamate; Fenbendazole) complexes were synthesized and characterized by elemental analysis, thermal, IR, EPR, UV-Vis, magnetic and conductance measurements. Geometry optimization, molecular electrostatic potential maps and natural bond orbital analysis were carried out at DFT/B3LYP/6-31G∗ level of theory. FBZ behaves as a neutral bidentate ligand via the pyridine-type nitrogen of the benzimidazole moiety and the carbamate group. Three-step ionization with pKa values of 3.38, 4.06 and 10.07 were reported for FBZ. The coordination of FBZ to the metal ions led to an increase in the antibacterial activity against the tested Staphylococcus aureus and Escherichia coli bacteria.

  17. Zinc(II) complexes containing bis-benzimidazole derivatives as a new class of apoptosis inducers that trigger DNA damage-mediated p53 phosphorylation in cancer cells. (United States)

    Liu, Shenggui; Cao, Wenqiang; Yu, Lianling; Zheng, Wenjie; Li, Linlin; Fan, Cundong; Chen, Tianfeng


    In the present study, two zinc(II) complexes containing bis-benzimidazole derivatives, Zn(bpbp)Cl2 (1) and [Zn(bpbp)2](ClO4)2·CH3CH2OH·H2O (2) (bpbp = 2,6-bis(1-phenyl-1H-benzo[d]imidazol-2-yl)pyridine), have been designed, synthesized and evaluated for their in vitro anticancer activities. The underlying molecular mechanisms through which they caused the cancer cell death were also elucidated. The complexes were identified as potent antiproliferative agents against a panel of five human cancer cell lines by comparing with cisplatin. Complex 2 demonstrated dose-dependent growth inhibition on MCF-7 human breast carcinoma cells with IC50 at 2.9 μM. Despite this potency, the complexes possessed great selectivity between human cancer cells and normal cells. Induction of apoptosis in MCF-7 cells by complex 2 was evidenced by accumulation of sub-G1 cell population, DNA fragmentation and nuclear condensation. Further investigation on intracellular mechanisms revealed that complex 2 was able to induce p53-dependent apoptosis in cancer cells by triggering DNA damage. On the basis of this evidence, we suggest that Zn(II) complexes containing bis-benzimidazole derivatives may be candidates for further evaluation as chemotherapeutic agents for human cancers.

  18. Design and synthesis of new benzimidazole-carbazole conjugates for the stabilization of human telomeric DNA, telomerase inhibition, and their selective action on cancer cells. (United States)

    Maji, Basudeb; Kumar, Krishan; Kaulage, Mangesh; Muniyappa, K; Bhattacharya, Santanu


    Cell-permeable small molecules that enhance the stability of the G-quadruplex (G4) DNA structures are currently among the most intensively pursued ligands for inhibition of the telomerase activity. Herein we report the design and syntheses of four novel benzimidazole-carbazole conjugates and demonstrate their high binding affinity to G4 DNA. S1 nuclease assay confirmed the ligand mediated G-quadruplex DNA protection. Additional evidence from Telomeric Repeat Amplification Protocol (TRAP-LIG) assay demonstrated efficient telomerase inhibition activity by the ligands. Two of the ligands showed IC50 values in the sub-micromolar range in the TRAP-LIG assay, which are the best among the benzimidazole derivatives reported so far. The ligands also exhibited cancer cell selective nuclear internalization, nuclear condensation, fragmentation, and eventually antiproliferative activity in long-term cell viability assays. Annexin V-FITC/PI staining assays confirm that the cell death induced by the ligands follows an apoptotic pathway. An insight into the mode of ligand binding was obtained from the molecular dynamics simulations.

  19. Biological evaluation of a cytotoxic 2-substituted benzimidazole copper(II) complex: DNA damage, antiproliferation and apoptotic induction activity in human cervical cancer cells. (United States)

    Qiao, Xin; Ma, Zhong-Ying; Shao, Jia; Bao, Wei-Guo; Xu, Jing-Yuan; Qiang, Zhao-Yan; Lou, Jian-Shi


    Exploring novel chemotherapeutic agents is a great challenge in cancer medicine. To that end, 2-substituted benzimidazole copper(II) complex, [Cu(BMA)Cl2]·(CH3OH) (1) [BMA = N,N'-bis(benzimidazol-2-yl-methyl)amine], was synthesized and its cytotoxicity was characterized. The interaction between complex 1 and calf thymus DNA was detected by spectroscopy methods. The binding constant (K b = 1.24 × 10(4 )M(-1)) and the apparent binding constant (K app = 6.67 × 10(6 )M(-1)) of 1 indicated its moderate DNA affinity. Complex 1 induced single strand breaks of pUC19 plasmid DNA in the presence of H2O2 through an oxidative pathway. Cytotoxicity studies proved that complex 1 could inhibit the proliferation of human cervical carcinoma cell line HeLa in both time- and dose-dependent manners. The results of nuclei staining by Hoechst 33342 and alkaline single-cell gel electrophoresis proved that complex 1 caused cellular DNA damage in HeLa cells. Furthermore, treatment of HeLa cells with 1 resulted in S-phase arrest, loss of mitochondrial potential, and up-regulation of caspase-3 and -9 in HeLa cells, suggesting that complex 1 was capable of inducing apoptosis in cancer cells through the intrinsic mitochondrial pathway.

  20. Benzimidazole derivative, BMT-1, induces apoptosis in multiple myeloma cells via a mitochondrial-mediated pathway involving H+/K+-ATPase inhibition. (United States)

    Yang, Tai; Li, Min-Hui; Liu, Jin; Huang, Ning; Li, Ning; Liu, Si-Nian; Liu, Yang; Zhang, Tao; Zou, Qiang; Li, Hua


    2-(1H-benzimidazol-2-yl)-4,5,6,7-tetrahydro-2H-indazol-3-ol (BMT-1), a bicyclic compound, belongs to the benzimidazole group and consists of the fusion of benzene and imidazole. The objective of the present study was to assess the effect of BMT-1 on the proliferation of multiple myeloma (MM) cells and identify whether BMT-1 induces apoptosis in MM cells. Our results showed a dose- and time-dependent decrease in the proliferation of MM cells treated with BMT-1. Further studies revealed that the antiproliferative effects of BMT-1 were caused by induction of apoptosis with activation of caspase-3 and cleavage of poly(ADP-ribose) polymerase in MM cells. In addition, BMT-1 induced the loss of mitochondrial membrane potential resulting in the activation of caspase-8 and -9. Furthermore, the MM cells treated with BMT-1 showed a more acidic intracellular pH (pHi) as indicated by a lower FL1/FL2 ratio caused by inhibition of H+/K+-ATPase. Collectively, these findings demonstrated that a decrease in pHi, caused by H+/K+-ATPase inhibition induced by BMT-1, triggered the dysfunction of the mitochondria resulting in the apoptosis of MM cells. Therefore, BMT-1 may be used as a lead compound for the design and development of new agents with which to treat MM and other forms of cancer.

  1. Design, optimization, and biological evaluation of novel keto-benzimidazoles as potent and selective inhibitors of phosphodiesterase 10A (PDE10A). (United States)

    Hu, Essa; Kunz, Roxanne K; Chen, Ning; Rumfelt, Shannon; Siegmund, Aaron; Andrews, Kristin; Chmait, Samer; Zhao, Sharon; Davis, Carl; Chen, Hang; Lester-Zeiner, Dianna; Ma, Ji; Biorn, Christopher; Shi, Jianxia; Porter, Amy; Treanor, James; Allen, Jennifer R


    Our development of PDE10A inhibitors began with an HTS screening hit (1) that exhibited both high p-glycoprotein (P-gp) efflux ratios in rat and human and poor metabolic stability. On the basis of cocrystal structure of 1 in human PDE10A enzyme, we designed a novel keto-benzimidazole 26 with comparable PDE10A potency devoid of efflux liabilities. On target in vivo coverage of PDE10A in rat brain was assessed using our previously reported LC-MS/MS receptor occupancy (RO) technology. Compound 26 achieved 55% RO of PDE10A at 30 mg/kg po and covered PDE10A receptors in rat brain in a dose-dependent manner. Cocrystal structure of 26 in PDE10A confirmed the binding mode of the novel scaffold. Further optimization resulted in the identification of keto-benzimidazole 34, which showed an increased in vivo efficacy of 57% RO in rats at 10 mg/kg po and an improved in vivo rat clearance and oral bioavailability.

  2. Chlorido[5-methoxy-1H-benzimidazole-2(3H-thione-κS]bis(triphenylphosphane-κPcopper(I methanol disolvate

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    Qing-Xuan Meng


    Full Text Available In the title complex, [CuCl(C8H8N2OS(C18H15P2]·2CH3OH, the CuI ion is coordinated by one chloride anion, one S atom from the 5-methoxy-1H-benzimidazole-2(3H-thione ligand and two P atoms from two triphenylphosphine ligands in a distorted tetrahedral geometry. One of the N-bound H atoms is involved in an intramolecular N—H...Cl hydrogen bond, while another one interacts with the solvent methanol molecule via an N—H...O hydrogen bond. Intermolecular O—H...Cl and O—H...O hydrogen bonds link two further complex molecules and four solvent molecules into a centrosymmetric structural unit. The short distance of 3.624 (4 Å between the centroids of the five- and the six-membered rings of two benzimidazole fragments indicates the presence of π–π interactions.

  3. Hexa-μ-chlorido-μ4-oxido-tetrakis({1-[(pyridin-2-ylmethyl]-1H-benzimidazole-κN3}copper(II

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    Hong Sun


    Full Text Available The title tetranuclear complex, [Cu4Cl6O(C13H11N34], features a tetrahedral arrangement of copper(II ions bonded to the central O atom (site symmetry overline{4}. Each of the six edges of the Cu4 tetrahedron is bridged by a chloride ion (one of which has site symmetry 2, so that each copper ion is linked to the other three metal ions through the central O atom and through three separate chloride-ion bridges. The fifth coordination position, located on the central Cu—O axis on the outside of the cluster, is occupied by an N atom of the monodentate 1-(pyridin-2-ylmethyl-1H-benzimidazole ligand. The resulting coordination geometry of the metal ion is a distorted trigonal bipyramid with the O and N atoms in the axial positions. The dihedral angle between the benzimidazole ring system and the pendant pyridine ring is 61.0 (2°.

  4. Effect of acetate and nitrate anions on the molecular structure of 3-(hydroxyimino)-2-butanone-2-(1H-benzimidazol-2-yl)hydrazone (United States)

    Kamat, Vinayak; Naik, Krishna; Revankar, Vidyanand K.


    A novel Schiff base ligand 3-(hydroxyimino)-2-butanone-2-(1H-benzimidazol-2-yl)hydrazone has been synthesized by the condensation reaction of 2-Hydrazinobenzimidazole with diacetyl monoxime in presence of acetic acid catalyst. The ligand has crystallized as its acetate salt, due to the charge-assisted hydrogen bonding between protonated benzimidazole ring and acetate anion. Efforts to synthesize the zinc(II) complex of the title compound, has resulted in the formation of a nitrate salt of the ligand, instead of coordination complex of zinc(II). Acetate salt has crystallized in monoclinic P 21/n, while the nitrate salt has crystallized in a triclinic crystal system with P -1 space group. Hirshfeld surface analysis is presented for both of the crystal structures. Structures of synthesized molecules are even computationally optimized using DFT. A comparative structural approach between the synthesized molecules and DFT optimized structure of bare ligand without any counterions is analyzed in terms of bond parameters. Hydrogen bonding is explained keeping the anions as the central dogma. Mass fragmentation pattern of the organic molecule and comparative account of IR, 1H and 13C NMR chemical shifts are also presented. Compounds are screened for their antibacterial and antifungal potencies against few pathogenic microorganisms. The organic motif is found be an excellent antifungal agent.

  5. Benzimidazole ligands in the corrosion inhibition for carbon steel in acid medium: DFT study of its interaction on Fe30 surface (United States)

    Garcia-Ochoa, E.; Guzmán-Jiménez, S. J.; Hernández, J. Guadalupe; Pandiyan, Thangarasu; Vásquez-Pérez, José M.; Cruz-Borbolla, Julián


    The corrosion inhibition of N,N‧-bis(benzimidazole-2-yl-methyl)amine (L1) and N, N‧-bis(benzimidazole-2-yl-methyl)hydroxyethylamine (L2) was analyzed by electrochemical and theoretical methods. The data show that ligands form an adsorption layer over an iron surface, obeying the Langmuir isotherm (Δ Gads° of -32.96 kJ mol-1); the value are higher than -20 kJ mol-1 but less than -40 kJ mol-1, belonging to a conversion stage of physical adsorption to chemical adsorption or a comprehensive adsorption. This is consistent with fractal dimension of the electrode surface, estimated by an impedance depression angle of a semicircle that the surface is homogeneously covered by the formation of an inhibitor film. Furthermore, the electronic parameters of the ligands were analyzed by DFT, showing that L1 and L2 possesses corrosion inhibition properties that give up its p orbital electron density through its HOMO orbital to the metal LUMO to form an adsorption layer, and this has been proved theoretically by the interaction of ligands with Fe30. In addition, we have collected corrosion inhibition data for around 70 organic compounds reported in the literature, and the inhibition data plotted against different inhibitors, showing that amine ligands are good corrosion inhibitors.

  6. cyclo-Tetra-μ-malato-κO,O',O'':O'''-tetra-kis[bis-(1H-benzimidazole-κN)cobalt(II)] eicosa-hydrate. (United States)

    Li, Jun-Hua; Nie, Jing-Jing; Su, Jian-Rong; Xu, Duan-Jun


    The title compound, [Co(4)(C(4)H(4)O(5))(4)(C(7)H(6)N(2))(8)]·20H(2)O, consists of tetra-nuclear Co(II) complexes and disordered uncoordinated water mol-ecules. The tetra-meric complex mol-ecule has symmetry. While two benzimidazole mol-ecules and a tridentate malate dianion coordinate a Co(II) ion, the carboxylate O atom from an adjacent malate dianion bridges the Co(II) ions to complete a distorted octa-hedral coordination geometry. The tridentate malate dianion chelates the Co(II) ion, and the chelate six- and five-membered rings show half-chair and envelope configurations, respectively. A face-to-face separation of 3.494 (9) Å between parallel benzimidazole ligands indicates the existence of π-π stacking between adjacent complexes. The crystal structure also involves N-H⋯O and O-H⋯O hydrogen bonds.

  7. Synthesis and PASS-assisted in silico approach of some novel 2-substituted benzimidazole bearing a pyrimidine-2, 4, 6(trione system as mucomembranous protector

    Directory of Open Access Journals (Sweden)

    Bijo Mathew


    Full Text Available Purpose: The present paper demonstrates the utility of PASS computer-aided program and makes a clear comparison of predicted and observed pharmacological properties of some novel 5-[(2E-1-(1H-benzimidazol-2-yl-3-substituted phenylprop-2-en-1-ylidene] pyrimidine-2, 4, 6 (1H, 3H, 5H-triones (5a-f. Materials and Methods: The synthesis of the titled derivatives were achieved by the reaction between 2E-1-(1H-benzimidazol-2-yl-3-phenylprop-2-en-1-ones (4a-f and barbituric acid in the presence of catalytic amount of acetic acid medium. All the final structures were assigned on the basis of IR, 1 HNMR and mass spectra analysis. All the newly synthesized compounds were screened for their antiulcer activity in the pylorus-ligated rats. Results: Compounds 5b, 5e and 5c showed a percentage protection of (69.58, 69.56 and 67.17 at a dose of 50 mg/kg b.w. when compared to standard omeprazole (77.37%, 2 mg/kg b.w.. Conclusion: Scanning of stomach specimens using electron microscope revealed that the mice treated with standard and synthetic derivatives had no injury observed in stomach mucosa, which is identical to that of the control animal.

  8. Role of annealing on the structural and optical properties of nanostructured diaceto bis-benzimidazole Mn(II) complex thin films. (United States)

    Praveen, P A; Babu, R Ramesh; Ramamurthi, K


    A coordination complex, manganese incorporated benzimidazole, thin films were prepared by chemical bath deposition method. Structural characterization of the deposited films, carried out by Fourier transform infrared spectroscopy, Raman and electron paramagnetic resonance spectral analyses, reveals the distorted tetrahedral environment of the metal ion with bis-benzimidazole ligand. Further the molecular composition of the deposited metal complex was estimated by energy-dispersive X-ray spectroscopy. The prepared thin films were thermally treated to study the effect of annealing temperature on the surface morphology and the results showed that the surface homogeneity of the films increased for thermally treated films up to 150°C. But distortion and voids were observed for the films annealed at 200°C. The Raman analysis reveals the molecular hydrogen bond distortion which leads to the evaporation of the metal complex from the thin film surface with respect to annealing temperature. The linear and nonlinear optical properties of the as prepared and annealed films were studied using ultraviolet-visible transmittance spectroscopy, second harmonic generation and Z-scan analyses. Films annealed at 150°C show a better linear transmittance in the visible region and larger SHG efficiency and third order nonlinear susceptibility when compared with the other samples. Further, the film annealed at 150°C was subjected to optical switching analysis and demonstrated to have an inverted switching behavior.

  9. Structure-activity relationships in cytotoxic Au(I)/Au(III) complexes derived from 2-(2'-pyridyl)benzimidazole. (United States)

    Maiore, Laura; Aragoni, Maria Carla; Deiana, Carlo; Cinellu, Maria Agostina; Isaia, Francesco; Lippolis, Vito; Pintus, Anna; Serratrice, Maria; Arca, Massimiliano


    Gold(I) and gold(III) complexes derived from 2-(2'-pyridyl)benzimidazole (pbiH) were proven to be a promising class of in vitro antitumor agents against A2780 human ovarian cancer cells. In this paper, a comparative electrochemical, UV-vis absorption, and emission spectroscopic investigation is reported on pbiH, the two mononuclear Au(III) complexes [(pbi)AuX2] (X = Cl (1), AcO (2)), the four mononuclear Au(I) derivatives [(pbiH)AuCl] (3), [(pbiH)Au(PPh3)]PF6 ((4(+))(PF6(-))), [(pbi)Au(PPh3)] (5), and [(pbi)Au(TPA)] (6), the three mixed-valence Au(III)/Au(I) complexes [(μ-pbi)Au2Cl3] (7), [(Ph3P)Au(μ-pbi)AuX2]PF6 (X = Cl ((8(+))(PF6(-))), AcO ((9(+))(PF6(-)))), and the binuclear Au(I)-Au(I) compound [(μ-pbi)Au2(PPh3)2]PF6 ((10(+))(PF6(-))). All complexes feature irreversible reduction processes related to the Au(III)/Au(I) or Au(I)/Au(0) processes and peculiar luminescent emission at about 360-370 nm in CH2Cl2, with quantum yields that are remarkably lower ((0.7-14.5) × 10(-2)) in comparison to that determined for the free pbiH ligand (31.5 × 10(-2)) in the same solvent. The spectroscopic and electrochemical properties of all complexes were interpreted on the grounds of time-dependent PBE0/DFT calculations carried out both in the gas phase and in CH2Cl2 implicitly considered within the IEF-PCM SCRF approach. The electronic structure of the complexes, and in particular the energy and composition of the Kohn-Sham LUMOs, can be related to the antiproliferative properties against the A2780 ovarian carcinoma cell line, providing sound quantitative structure-activity relationships and shedding a light on the role played by the global charge and nature of ancillary ligands in the effectiveness of Au-based antitumor drugs.

  10. Intracellular detection of Cu(2+) and S(2-) ions through a quinazoline functionalized benzimidazole-based new fluorogenic differential chemosensor. (United States)

    Paul, Anup; Anbu, Sellamuthu; Sharma, Gunjan; Kuznetsov, Maxim L; Guedes da Silva, M Fátima C; Koch, Biplob; Pombeiro, Armando J L


    A new quinazoline functionalized benzimidazole-based fluorogenic chemosensor H3L is synthesized and fully characterized by conventional techniques including single crystal X-ray analysis. It acts as a highly selective colorimetric and fluorescence sensor for Cu(2+) ions in DMF/0.02 M HEPES (1 : 1, v/v, pH = 7.4) medium. Reaction of H3L with CuCl2 forms a mononuclear copper(ii) [Cu(Cl)(H2L)(H2O)] (H2L-Cu(2+)) complex which is characterized by conventional techniques and quantum chemical calculations. Electronic absorption and fluorescence titration studies of H3L with different metal cations show a distinctive recognition only towards Cu(2+) ions even in the presence of other commonly coexisting ions such as Li(+), Na(+), K(+), Mg(2+), Ca(2+), Fe(2+), Fe(3+), Mn(2+), Co(2+), Ni(2+), Zn(2+), Cd(2+) and Hg(2+). Moreover, H2L-Cu(2+) acts as a metal based highly selective and sensitive chemosensor for S(2-) ions even in the presence of other commonly coexisting anions such as F(-), Cl(-), Br(-), I(-), SO4(2-), SCN(-), AcO(-), H2PO4(-), PO4(3-), NO3(-), ClO4(-), NO2(-), HSO4(-), HSO4(2-), S2O3(2-), S2O8(2-), CN(-), CO3(2-) and HCO3(-) in DMF/0.02 M HEPES (1 : 1, v/v, pH = 7.4) medium. Quantification analysis indicates that these receptors, H3L and H2L-Cu(2+), can detect the presence of Cu(2+) and S(2-) ions at very low concentrations of 1.6 × 10(-9) M and 5.2 × 10(-6) M, respectively. The propensity of H3L as a bio-imaging fluorescent probe for detection of Cu(2+) ions and sequential detection of S(2-) ions by H2L-Cu(2+) in Dalton lymphoma (DL) cancer cells is also shown.

  11. Synthesis, crystal structure determination and antiproliferative activity of novel 2-amino-4-aryl-4,10-dihydro[1,3,5]triazino[1,2- a]benzimidazoles (United States)

    Hranjec, Marijana; Pavlović, Gordana; Karminski-Zamola, Grace


    This manuscript describes the synthesis of novel 2-amino-4-aryl-4,10-dihydro-[1,3,5]triazino[1,2- a]benzimidazoles as hydrochloride salts 4a-n and 5b which were prepared in the reaction of cyclocondensation between 2-guanidinobenzimidazole and versatile heteroaromatic aldehydes. Structures of all prepared compounds have been studied by using 1H and 13C NMR, IR and UV/Vis spectroscopy. The crystal and molecular structure of 4f was determined by X-ray diffraction on single crystals. The molecule of 2-amino-4-(4'-methylphenyl)-4,10-dihydro[1,3,5]triazino[1,2- a]benzimidazole hydrochloride 4f (C 16H 16N 5+·Cl -) exists in the solid state in one of the possible tautomeric forms, being protonated at the one of the nitrogen atoms of the 1,4-dihydrotriazine ring. The molecule is highly delocalized within the 4,10-dihydro[1,3,5]triazino[1,2- a]benzimidazole moiety with the highest deviation from the plane for the methine carbon atom and the protonated nitrogen atom of the 1,4-dihydrotriazine ring. The cations are joined via N-H⋯N hydrogen bonds into R22(8) centrosymmetric dimers. Cation dimers are further connected with Cl - ions via N-H⋯Cl and C-H⋯Cl hydrogen bonds into 2D chains spreading along the b axis. The obtained single-crystal X-ray structure determination unequivocally confirms tautomeric form of the compound present in the solid-state and can represent tantative pattern for other prepared compounds. All prepared compounds were tested on their antiproliferative activity in vitro on several human cancer cell lines. Compound 4m was the most active one (IC 50 ≈ 20 μM), while compounds 4d, 4f, 4k, 4l4m showed moderate, but non-selective, antiproliferative activity with IC 50 25-60 μM.

  12. Bis[2-(2-aminoethyl-1H-benzimidazole-κ2N2,N3](nitrato-κ2O,O′cobalt(II chloride trihydrate

    Directory of Open Access Journals (Sweden)

    Jing Zhao


    Full Text Available In the title compound, [Co(NO3(C9H11N32]Cl·3H2O, the CoII atom is coordinated by four N atoms from two chelating 2-(2-aminoethyl-1H-benzimidazole ligands and two O atoms from one nitrate anion in a distorted octahedral coordination environment. In the crystal, N—H...Cl, N—H...O, O—H...Cl and O—H...O hydrogen bonds link the complex cations, chloride anions and solvent water molecules into a three-dimensional network. π–π interactions between the imidazole and benzene rings and between the benzene rings are observed [centroid–centroid distances = 3.903 (3, 3.720 (3, 3.774 (3 and 3.926 (3 Å].

  13. Lanthanide(III and Yttrium(III Complexes of Benzimidazole-2-Acetic Acid: Synthesis, Characterisation and Effect of La(III Complex on Germination of Wheat

    Directory of Open Access Journals (Sweden)


    Full Text Available The synthesis and characterisation of lanthanide(III and yttrium(III nitrate complexes of benzimidazole-2-acetic acid (HBIA are reported. The complexes have been characterised by elemental analysis, molar conductance, magnetic studies, IR, 1 H NMR, UV-visible, EPR, and TG/DTA studies. They have the stoichiometry [ Ln 3 ( BIA 2 ( NO 3 7 ( H 2 O 4 ]⋅3 H 2 O where Ln=La(III, Pr(III, Nd(II, Sm(III, Eu(III, Gd(III, Tb(III, Dy(III, and Y(III. The effect of La(III complex on germination, coleoptile, and root length of two local varieties of wheat DWR-195 and GW-349 for different treatment periods has been investigated. The complex was found to exhibit enhanced activity, compared to HBIA or metal salt alone at lower treatment periods.

  14. Design, synthesis, quantum chemical studies and biological activity evaluation of pyrazole-benzimidazole derivatives as potent Aurora A/B kinase inhibitors. (United States)

    Zheng, Youguang; Zheng, Ming; Ling, Xin; Liu, Yi; Xue, Yunsheng; An, Lin; Gu, Ning; Ji, Min; Jin, Min


    Novel pyrazole-benzimidazole derivatives have been designed and synthesized. The entire target compounds were determined against cancer cell lines U937, K562, A549, LoVo and HT29 and were screened for Aurora A/B kinase inhibitory activity in vitro. The compounds 7a, 7b, 7i, 7k and 7l demonstrated significant cancer cell lines and Aurora A/B kinase inhibitory activities. Molecular modeling studies suggested the derivatives have bound in the active site of Aurora A kinase through the formation of four hydrogen bonds. Quantum chemical studies were carried out on these compounds to understand the structural features essential for activity. The cellular activity of 7k was also tested by immunofluorescence.

  15. Benzimidazoles as new scaffold of sirtuin inhibitors: green synthesis, in vitro studies, molecular docking analysis and evaluation of their anti-cancer properties. (United States)

    Yoon, Yeong Keng; Ali, Mohamed Ashraf; Wei, Ang Chee; Shirazi, Amir Nasrolahi; Parang, Keykavous; Choon, Tan Soo


    Two series of novel benzimidazole derivatives were designed, synthesized and evaluated for their SIRT1 and SIRT2 inhibitory activity. Among the newly synthesized compounds, compound 4j displayed the best inhibitory activity for SIRT1 (IC50 = 54.21 μM) as well as for SIRT2 (IC50 = 26.85 μM). Cell proliferation assay showed that compound 4j possessed good antitumor activity against three different types of cancer cells derived from colon (HCT-116), breast (MDA-MB-468) and blood-leukemia (CCRF-CEM) with cell viability of 40.0%, 53.2% and 27.2% respectively at 50 μM. Docking analysis of representative compound 4j into SIRT2 indicated that the interaction with receptor was primarily due to hydrogen bonding and π-π stacking interactions.

  16. Synthesis, biological evaluation, and molecular docking studies of novel 1-benzene acyl-2-(1-methylindol-3-yl)-benzimidazole derivatives as potential tubulin polymerization inhibitors. (United States)

    Wang, Yan-Ting; Qin, Ya-Juan; Yang, Na; Zhang, Ya-Liang; Liu, Chang-Hong; Zhu, Hai-Liang


    A series of 1-benzene acyl-2-(1-methylindol-3-yl)-benzimidazole derivatives were designed, synthesized and evaluated as potential tubulin polymerization inhibitors and for the cytotoxicity against anthropic cancer cell lines. Among the novel compounds, compound 11f was demonstrated the most potent tubulin polymerization inhibitory activity (IC50 = 1.5 μM) and antiproliferative activity against A549, HepG2 and MCF-7 (GI50 = 2.4, 3.8 and 5.1 μM, respectively), which was compared with the positive control colchicine and CA-4. We also evaluated that compound 11f could effectively induce apoptosis of A549 associated with G2/M phase cell cycle arrest. Docking simulation and 3D-QSAR model in these studies provided more information that could be applied to design new molecules with more potent tubulin inhibitory activity.

  17. Design, synthesis and biological evaluation of novel 5-fluoro-1H-benzimidazole-4-carboxamide derivatives as potent PARP-1 inhibitors. (United States)

    Wang, Junwei; Wang, Xuyan; Li, Hui; Ji, Dezhong; Li, Yuyan; Xu, Yungen; Zhu, Qihua


    A series of novel 5-fluorine-benzimidazole-4-carboxamide analogs were designed and synthesized. All target compounds were evaluated for their PARP-1 inhibitory activity. Compounds possessed high intrinsic PARP-1 inhibitory potency have been evaluated in vitro cellular assays to measure the potentiation effect of cytotoxic agents against cancer cell line. These efforts led to the identification of compound 10f, which displayed strong inhibition against the PARP-1 enzyme with an IC50 of 43.7nM, excellent cell inhibitory activity in HCT116 cells (IC50=7.4μM) and potentiation of temozolomide cytotoxicity in cancer cell line A549 (PF50=1.6).

  18. VUV photophysics and dissociative photoionization of pyrimidine, purine, imidazole and benzimidazole in the 7-18 eV photon energy range

    Energy Technology Data Exchange (ETDEWEB)

    Schwell, Martin [Laboratoire Interuniversitaire des Systemes Atmospheriques (LISA), CNRS-UMR 7583, Universite Paris 7 and 12, 61 Avenue du General de Gaulle, 94010 Creteil (France)], E-mail:; Jochims, Hans-Werner; Baumgaertel, Helmut [Institut fuer Physikalische und Theoretische Chemie der Freien Universitaet Berlin, Takustr. 3, Berlin 14195 (Germany); Leach, Sydney [Laboratoire d' Etude du Rayonnement et de la Matiere en Astrophysique (LERMA), CNRS-UMR 8112, Observatoire de Paris-Meudon, 5 Place Jules-Janssen, 92195 Meudon (France)], E-mail:


    Photoionization mass spectrometry is used to study ionization processes and fragmentation pathways of four prebiotic species, pyrimidine, purine, imidazole and benzimidazole, in the 7-18 eV photon energy region, with synchrotron radiation as excitation source. These molecules are possible precursors of the nucleic acid bases that occur in DNA and RNA. Ionization energies and ion appearance energies are reported. They are compared with electron impact and other studies and are discussed in terms of the electronic and nuclear structures of these species and their cations. The ion appearance energies, in conjunction with thermochemical data, were used to propose dissociative photoionization pathways, principally involving loss of HCN molecules in each of the four species. Astrophysical implications of the results concern the prospects for observation and survival of these molecules in the interstellar medium, in comets and in meteorites. Suggestions are made concerning suitable sites for radioastronomical searches for these purines and pyrimidines.

  19. Synthesis of a Dehydroabietyl Derivative Bearing a 2-(2′-Hydroxyphenyl Benzimidazole Unit and Its Selective Cu2+ Chemosensing

    Directory of Open Access Journals (Sweden)

    Ying-Ming Pan


    Full Text Available A dehydroabietyl derivative 2 bearing a 2-(2′-hydroxyphenylbenzimidazole unit was synthesized and its sensing behaviors toward metal ions were investigated by UV-Vis and fluorescence spectroscopy methods. In THF solution, compound 2 exhibited excellent selectivity for Cu(II over miscellaneous other metal ions including Cr(II, Mn(II, Co(II, Ni(II, Zn(II, Cd(II, Al(III, Mg(II, Pb(II, Hg(II, Na(I, Li(I and K(I evidenced through the quenching of the fluorescence of the benzimidazole fragment. The reaction between 2 and Cu2+ was found to be stoichiometric with the formation of a 1:1 complex.

  20. Crystal structures and luminescence properties of two Cd(II) complexes based on 2-(1H-imidazol-1methyl)-6-methyl-1H-benzimidazole

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yuhong; Meng, Xiangru; Wen, Yu; Li, Peng; Ma, Lin [Zhengzhou Univ. (China). College of Chemistry and Molecular Engineering; Zhang, Qiuju [Zhengzhou Univ. (China). Clinical Testing Section


    Two new complexes, {[Cd(immb)I_2].DMF}{sub n} (1) and {[Cd_3(immb)(btc)_2]. H_2O}{sub n} (2) (immb = 2-(1H-imidazol- 1-methyl)-6-methyl-1H-benzimidazole, btc = 1,2,3-benzenetricarboxylate, DMF = dimethyl formamide), have been synthesized and characterized. Single crystal X-ray diffraction shows that 1 exhibits a chain structure constructed by immb ligands bridging Cd(II) ions. In 2, Cd(II) ions are linked by immb ligands with bridging mode and btc3- anions with the μ{sub 2}-η{sup 2}:η{sup 1} bonding pattern leading to a 2D structure. Luminescent properties have been investigated in the solid state at room temperature.

  1. Acid-base blend membranes based on 2-amino-benzimidazole and sulfonated poly(ether ether ketone) for direct methanol fuel cells

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Yongzhu; Manthiram, Arumugam [Materials Science and Engineering Program, The University of Texas at Austin, Austin, TX 78712 (United States); Guiver, Michael D. [Institute for Chemical Process and Environmental Technology, National Research Council of (Canada)


    Direct methanol fuel cells (DMFC) are attractive for portable and automobile power needs, but their commercialization is hampered by high methanol permeability and the high cost of the currently used Nafion membrane. We report here a novel, low-cost blend membrane consisting of polysulfone-2-amide-benzimidazole (a basic polymer) and sulfonated poly(ether ether ketone) (an acidic polymer), which facilitates proton conduction through acid-base interactions while preserving excellent chemical and mechanical stabilities. The blend membrane exhibits performance in DMFC much higher than that of Nafion 115 and similar to that of Nafion 112, but with a remarkably superior long-term performance than Nafion 112 due to significantly reduced methanol crossover, enhancing the commercialization prospects of DMFC. (author)

  2. Synthesis, Characterization, Spectroscopic Properties of 2-(4-Dimethylaminophenyl)-5-fluoro-6-(morpholin-4-yl)-1H-benzimidazole and its Interaction with Calf Thymus DNA

    Institute of Scientific and Technical Information of China (English)

    Ling Tian TANG; Yi WANG; Xin Qi LIU; Shao Wen HU; Tai Wei CHU; Xiang Yun WANG


    2-(4-Dimethylaminophenyl)-5-fluoro-6-(morpholin-4-yl)- 1H-benzimidazole(1) has been synthesized and characterized by 1H-NMR, MS and elemental analysis. UV-Vis spectra of the aqueous solutions at different pH values reveal that compound 1 can combine three protons. Its three protonation constants are determined by spectrophotometry and calculated by non-linear least squares. The results of steady-state fluorescence measurements indicate that a special interaction occurs between compound 1 and calf thymus DNA, of which the binding constant, Kb, is (2.30 ±0.10)×l04 L/mol. Compound 1 in the concentration range of 10-8 to 1.2×l0-6 mol/L could be used for quantitative determination of DNA.

  3. catena-Poly[[(diiodidocadmium-μ-{1-[(1H-benzimidazol-2-ylmethyl]-1H-imidazole-κ2N:N′}] N,N-dimethylformamide monosolvate

    Directory of Open Access Journals (Sweden)

    Bingtao Liu


    Full Text Available In the title complex, {[CdI2(C11H10N4]·C3H7NO}n, the CdII ion is four-coordinated by two N atoms from two 1-[(1H-benzimidazol-1-ylmethyl]-1H-imidazole (bmi ligands and by two terminal I− anions in a distorted tetrahedral geometry. One of the two I− anions is disordered over two sets of sites, with refined occupancies of 0.66 (5 and 0.34 (5. The CdII ions are bridged by bmi ligands, leading to the formation of a chain along [001]. Dimethylformamide solvent molecules are located between these chains. Classical N—H...O hydrogen bonding between the bmi ligands and the solvent molecules leads to a consolidation of the structure.

  4. 2-Arylbenzothiazole, benzoxazole and benzimidazole derivatives as fluorogenic substrates for the detection of nitroreductase and aminopeptidase activity in clinically important bacteria. (United States)

    Cellier, Marie; Fabrega, Olivier J; Fazackerley, Elizabeth; James, Arthur L; Orenga, Sylvain; Perry, John D; Salwatura, Vindhya L; Stanforth, Stephen P


    A series of 2-(2-nitrophenyl)benzothiazole 7, 2-(2-nitrophenyl)benzoxazole 10 and 2-(2-nitrophenyl)benzimidazole 13 derivatives have been synthesised and assessed as indicators of nitroreductase activity across a range of clinically important Gram negative and Gram positive bacteria. The majority of Gram negative bacteria produced strongly fluorescent colonies with substrates 7 and 10 whereas fluorescence production in Gram positive bacteria was less widespread. The l-alanine 16 and 19 and β-alanine 21 and 23 derivatives have been prepared from 2-(2-aminophenyl)benzothiazole 14 and 2-(2-aminophenyl)benzoxazole 17. These four compounds have been evaluated as indicators of aminopeptidase activity. The growth of Gram positive bacteria was generally inhibited by these substrates but fluorescent colonies were produced with the majority of Gram negative bacteria tested.

  5. Synthesis, characterization, self-assembly, gelation, morphology and computational studies of alkynylgold(III) complexes of 2,6-bis(benzimidazol-2'-yl)pyridine derivatives. (United States)

    Yim, King-Chin; Lam, Elizabeth Suk-Hang; Wong, Keith Man-Chung; Au, Vonika Ka-Man; Ko, Chi-Chiu; Lam, Wai Han; Yam, Vivian Wing-Wah


    A novel class of alkynylgold(III) complexes of the dianionic ligands derived from 2,6-bis(benzimidazol-2'-yl)pyridine (H2bzimpy) derivatives has been synthesized and characterized. The structure of one of the complexes has also been determined by X-ray crystallography. Electronic absorption studies showed low-energy absorption bands at 378-466 nm, which are tentatively assigned as metal-perturbed π-π* intraligand transitions of the bzimpy(2-) ligands. A computational study has been performed to provide further insights into the nature of the electronic transitions for this class of complexes. One of the complexes has been found to show gelation properties, driven by π-π and hydrophobic-hydrophobic interactions. This complex exhibited concentration- and temperature-dependent (1)H NMR spectra. The morphology of the gel has been characterized by transmission electron microscopy (TEM) and scanning electron microscopy (SEM).

  6. Chloridobis[2-(1,3-thiazol-4-yl-κN-1H-benzimidazole-κN3]cobalt(II chloride dihydrate

    Directory of Open Access Journals (Sweden)

    Zhan-Wang Shi


    Full Text Available In the title compound, [CoCl(C10H7N3S2]Cl·2H2O, the CoII atom is five-coordinated by four N atoms from two chelating 2-(1,3-thiazol-4-yl-1H-benzimidazole ligands and one Cl atom in a distorted trigonal–bipyramidal geometry. In the crystal, N—H...O and O—H...Cl hydrogen bonds and π–π interactions between the thiazole, imidazole and benzene rings [centroid-to-centroid distances 3.546 (2, 3.683 (2 and 3.714 (2 Å] link the complex cations, chloride anions and uncoordinating water molecules into a three-dimensional network.

  7. Dichlorido{2-[(5-methyl-1H-pyrazol-3-yl-κN2methyl]-1H-1,3-benzimidazole-κN3}zinc

    Directory of Open Access Journals (Sweden)

    Karim Chkirate


    Full Text Available The asymmetric unit of the title complex, [ZnCl2(C12H12N4], contains two independent molecules having similar conformations. The coordination about the ZnII atom is distorted tetrahedral, with the geometrical constraints of the chelating ligand responsible for the observed distortion. Each of the independent molecules forms chains in the crystal through pairs of N—H...Cl hydrogen bonds, using the pyrazole and benzimidazole N—H groups as donors. The first molecule forms chains running parallel to the b axis, while the other molecule affords the same kind of one-dimensional supramolecular structure parallel to the a axis. The structure was refined as a two-component twin with BASF = 0.0437 (4.

  8. Effect of optimized structure and electronic properties of some benzimidazole derivatives on corrosion inhibition of mild steel in hydrochloric acid medium: Electrochemical and theoretical studies

    Indian Academy of Sciences (India)

    Alokdut Dutta; Sujit Sankar Panja; M M Nandi; Dipankar Sukul


    The corrosion inhibitive action of a few benzimidazole derivatives namely 2-(benzamido) ethylbenzimidazole (BAEBI), 2-(-benzenesulphonamido) ethylbenzimidazole (BSAEBI), 2-(benzamido) methylbenzimidazole (BAMBI) and 2-(-benzenesulphonamido) methylbenzimidazole (BSAMBI), towards mild steel in hydrochloric acid has been studied using potentiodynamic polarization and electrochemical impedance spectroscopic (EIS) methods. The results show that these compounds get adsorbed on the mild steel surface following Temkin adsorption isotherm, and act as mixed-type inhibitors. The inhibition efficiencies are found to follow the order, BAEBI > BSAEBI > BAMBI > BSAMBI. This observation is explained in terms of chain length, relative effects of amido and sulphonamido groups, possible structural factors, spatial orientations, energy gap between the frontier molecular orbitals, different intrinsic molecular parameters, like, global hardness and softness, and number of electrons transferred.

  9. Synthesis, DNA binding, cellular DNA lesion and cytotoxicity of a series of new benzimidazole-based Schiff base copper(II) complexes. (United States)

    Paul, Anup; Anbu, Sellamuthu; Sharma, Gunjan; Kuznetsov, Maxim L; Koch, Biplob; Guedes da Silva, M Fátima C; Pombeiro, Armando J L


    A series of new benzimidazole containing compounds 2-((1-R-1-H-benzimidazol-2-yl)phenyl-imino)naphthol HL(1-3) (R = methyl, ethyl or propyl, respectively) have been synthesized by Schiff base condensation of 2-(1-R-1-H-benzo[d]imidazol-2-yl)aniline and 2-hydroxy-1-naphthaldehyde. The reactions of HL(1-3) with Cu(NO3)2·2.5H2O led to the corresponding copper(II) complexes [Cu(L)(NO3)] 1-3. All the compounds were characterized by conventional analytical techniques and, for 1 and 3, also by single-crystal X-ray analysis. The interactions of complexes 1-3 with calf thymus DNA were studied by absorption and fluorescence spectroscopic techniques and the calculated binding constants (K(b)) are in the range of 3.5 × 10(5) M(-1)-3.2 × 10(5) M(-1). Complexes 1-3 effectively bind DNA through an intercalative mode, as proved by molecular docking studies. The binding affinity of the complexes decreases with the size increase of the N-alkyl substituent, in the order of 1 > 2 > 3, which is also in accord with the calculated LUMO(complex) energies. They show substantial in vitro cytotoxic effect against human lung (A-549), breast (MDA-MB-231) and cervical (HeLa) cancer cell lines. Complex 1 exhibits a significant inhibitory effect on the proliferation of the A-549 cancer cells. The antiproliferative efficacy of 1 has also been analysed by a DNA fragmentation assay, fluorescence activated cell sorting (FACS) and nuclear morphology using a fluorescence microscope. The possible mode for the apoptosis pathway of 1 has also been evaluated by a reactive oxygen species (ROS) generation study.

  10. Conformation driven complexation of two analogous benzimidazole based tripodal ligands with Ag(I) resulting in a trigonal prism and a coordination polymer

    Indian Academy of Sciences (India)

    Suman Bhattacharya; Binoy K Saha


    Two analogous tripodal ligands, namely, 1,3,5-tris(benzimidazol-1-ylmethyl)-2,4,6-triethylbenzene (1-Et) and 1,3,5-tris(benzimidazol-1-ylmethyl)-2,4,6-trimethoxybenzene (1-OMe) have been used for complexation with silver(I) tetrafluoroborate. A trinuclear Ag(I) salt, formulated as $\\mathbf{[Ag_3(1-Et)_2]^{3+}(BF_4){}^{−}_{3}\\bullet 7CH_3CN\\bullet yH_2O}$ was formed in the complexation reaction of 1-Et with silver(I) tetrafluoroborate, which consists of a trigonal prismatic cation formed by three bicoordinated Ag(I) coordinated with two 1-Et ligands. In case of the 1-OMe ligand, however, a one dimensional ladder, formulated as $\\mathbf{[(Ag(1-OMe)OH_2)^{+}(BF_4)^{−}\\bullet MeOH]_{\\infty}}$ was obtained which is constituted of a tetracoordinated Ag(I) center in a distorted tetrahedral environment. The crystal structures of the ligand hydrates namely $\\mathbf{1-Et\\bullet H_2O}$ and $\\mathbf{1-OMe\\bullet 3.6H_2O}$ have been discussed along with the structure of methanol solvate-hydrate of 1-Et. The imidazole rings of the Bim groups in 1-Et in the crystal structures of the ligand as well as in its coordination complex with the Ag(I) are pointed inward with respect to the central ring, whereas it is pointed outwards in the crystal structures of 1-OMe as well as its Ag(I) complex.

  11. 1-(5-Carboxyindol-1-yl)propan-2-ones as inhibitors of human cytosolic phospholipase A2alpha: synthesis and properties of bioisosteric benzimidazole, benzotriazole and indazole analogues. (United States)

    Bovens, Stefanie; Kaptur, Martina; Elfringhoff, Alwine Schulze; Lehr, Matthias


    The indole ring systems of the cytosolic phospholipase A(2)alpha (cPLA(2)alpha) inhibitor 1-[3-(4-octylphenoxy)-2-oxopropyl]indole-5-carboxylic acid (2) and the isomeric 6-carboxylic acid (3) were replaced by benzimidazole, benzotriazole and indazole scaffolds, respectively. The effect of the structural variations on cPLA(2)alpha inhibitory potency, metabolic stability and solubility was studied. The lead 2 and the indazole-5-carboxylic acid 28 were the metabolically most stable compounds in an assay with rat liver microsomes, while the benzimidazole-5-carboxylic acid derivative 13 possessed the best water solubility (22 microg/mL at pH 7.4). The indazole-5-carboxylic acid 28 revealed the highest cPLA(2)alpha inhibitory potency of the compounds in this series. With an IC(50)-value of 0.005 microM it was about sevenfold more active than the lead 2.

  12. Comparison of experimental and DFT-calculated NMR chemical shifts of 2-amino and 2-hydroxyl substituted phenyl benzimidazoles, benzoxazoles and benzothiazoles in four solvents using the IEF-PCM solvation model. (United States)

    Pierens, Gregory K; Venkatachalam, T K; Reutens, David C


    A comparative study of experimental and calculated NMR chemical shifts of six compounds comprising 2-amino and 2-hydroxy phenyl benzoxazoles/benzothiazoles/benzimidazoles in four solvents is reported. The benzimidazoles showed interesting spectral characteristics, which are discussed. The proton and carbon chemical shifts were similar for all solvents. The largest chemical shift deviations were observed in benzene. The chemical shifts were calculated with density functional theory using a suite of four functionals and basis set combinations. The calculated chemical shifts revealed a good match to the experimentally observed values in most of the solvents. The mean absolute error was used as the primary metric. The use of an additional metric is suggested, which is based on the order of chemical shifts. The DP4 probability measures were also used to compare the experimental and calculated chemical shifts for each compound in the four solvents. Copyright © 2015 John Wiley & Sons, Ltd.

  13. Vibrationally resolved ¹Lb (¹A')↔S0 (¹A') electronic spectra of benzimidazole and indene: Influence of Duschinsky and Herzberg-Teller effects on weak dipole-allowed transitions. (United States)

    Yang, Pan; Pang, Min; Li, Ming; Shen, Wei; He, Rongxing


    Geometrical optimizations of the ground and first excited states of benzimidazole and indene were performed using the density functional theory (DFT) and its time-dependent extension methods (TD-DFT), respectively. Their vibrationally resolved (1)Lb ((1)A')↔S0 ((1)A') absorption and fluorescence spectra were simulated within the Franck-Condon approximation including the Herzberg-Teller (HT) and Duschinsky effects. Calculated results revealed that, with the HT and Duschinsky effects getting involved, the simulated weak (1)Lb ((1)A')↔S0 ((1)A') electronic spectra of the two molecules excellently reproduce the experimental findings. Based on the experimental data and other theoretical results, we tentatively assigned most of the vibrational normal modes which emerged in the experimental spectra of the two molecules. The present theoretical insights are expected to help us understand the nature of electronic transitions in the vibrationally resolved absorption and fluorescence spectra of benzimidazole and its analogues.

  14. 苯并咪唑对雄性大鼠生育力的影响%Effect of benzimidazole on fertility in male rats

    Institute of Scientific and Technical Information of China (English)

    于功昌; 王筱芬; 谢琳; 刘衍忠; 李莉


    Objective To study the effect of benzimidazole on male rats fertility and its effect target. Methods A total of 100 healthy male Wistar rats were randomly divided into four groups. The rats in low-dose, moderate-dose and high-dose groups were treated with benzimidazole by gavage at the doses of 20, 100 and 200 mg/kg once a day for 80 consecutive days,while 0.5% tween 80 solution was given to the control. After treatment, the male rats were mated with females at a ratio of 1:1 for five days, and the successful mating rate and the fertility index were observed. After mating, the testis and epididymidis were immediately excised. Then the bilateral testes were weighed, and the testis coefficient was calculated. The sperm motility and counts of the left cauda epididymidis were determined. The levels of serum hormone (LH, FSH, T), histopathological changes and the cell cycle of testis were detected by radio—immunity method, HE staining and flow cytometry, respectively. Results In comparison with control group, the successful mating rates were increased and the fertility indexes were decreased in high-dose and moderate—dose groups exposed to benzimidazole (P<0.05, P<0.01). In high—dose and moderate—dose groups, atrophic testis, decreased testis coefficient, and decreased sperm motility and counts were observed (P<0.01). There were no obvious differences in the levels of FSH and T between treatment and control groups. The level of serum LH in high-dose group was lower than that in control group (P<0.05). Atrophic seminiferous tubules, disordered and decreased germ cells, increased degeneration, edema and sloughing of germ cells were observed. The cells in G0/G1, S phases decreased, the accounts of cells in G2/M increased with the increase of benzimidazole dose (P<0.05, P<0.01). Conclusion Benzimidazole has adverse effect on spermatogenic function in male rats, may cause spermatogenic failure, resulting in decreased fertility or infertility.%目的 探讨苯并咪

  15. Synthesis of N - Alkyl Benzimidazoles as Corrosion Inhibitors for Acidification in Hydrochloric Acid and Evaluation of Their Inhibition Performance%N-烷基苯并咪唑酸化缓蚀剂的合成及性能

    Institute of Scientific and Technical Information of China (English)

    杨鹏辉; 冀生辉


    Four kinds of N - alkyl benzimidazole corrosion inhibitors were synthesized by alkylation of 2 - methyl benzimidazole or 2 - ethyl benzimidazole. The corrosion inhibition performance of as - synthesized inhibitors was evaluated by static state weight loss test and dynamic potential scanning polarization curve measurement. It was found that properly extending carbon chain of benzimidazole helped to improve the anticorrosion ability of benzimidazoles, and corrosion inhibitor N - hexadecyl - 2 - ethyl benzimidazole showed the best corrosion inhibition performance. Besides, at 60 ℃ in 15% hydrochloric acid, the corrosion rate of N80 steel decreased with increasing concentration of the corrosion inhibitor; and the corrosion rate of the steel at a corrosion inhibitor concentration of 1.0% was 1.73g/(m2 · h) , which indicated that corrosion inhibitor N-hexadecyl-2-ethyl benzimidazole was advantageous over the first-class corrosion inhibitor for acidification. Moreover, as-synthesized corrosion inhibitors were a class of mixed-type inhibitors dominated by cathode inhibition, but their inhibition performance in HCl with a concentration of above 20 % or at a temperature of above 70 ℃ was undesirable.%苯并咪唑是一类环境友好的缓蚀剂,将其衍生物用作油气田酸化缓蚀剂的报道较少.通过烷基化反应在2-甲基苯并咪唑和2-乙基苯并咪唑的1-氮原子上分别引入十二烷基和十六烷基,合成了4种N-烷基苯并咪唑,并以其为主剂制成缓蚀剂,用静态失重法和动电位扫描极化曲线对4种复配缓蚀剂在盐酸溶液中的缓蚀性能进行了评价.结果表明:适当延长1位烷基碳链,有助于提高苯并咪唑衍生物的缓蚀能力;合成的4种N-烷基苯并咪唑中,以N-十六烷基-2-乙基苯并咪唑为主剂制成缓蚀剂d的缓蚀性能最好;在60℃,15%HCl中,N80钢的腐蚀速率随缓蚀剂d用量的增大而减小,其用量为1.0%时,N80钢腐蚀速率为1.73 g/(m2·h),优于

  16. Detection of benzimidazole resistance in gastrointestinal nematodes of sheep and goats of sub-Himalyan region of northern India using different tests. (United States)

    Rialch, Ajayta; Vatsya, Stuti; Kumar, Rajeev Ranjan


    The present investigation was planned with the objective of studying the status of benzimidazole (BZ) resistance in gastrointestinal nematodes (GIN) of sheep and goats of different agro-climatic zones of sub-Himalyan region of northern India using in vivo faecal egg count reduction test (FECRT) and in vitro tests namely egg hatch assay (EHA) and larval development assay (LDA). Out of fourteen flocks, FECRT detected resistance in eight flocks (two sheep flocks and six goat flocks) with FECR% ranging from 54.95 to 90.86. Pre treatment coproculture contained predominantly Haemonchus contortus, followed by Trichostrongylus spp., Oesophagostomum and Strongyloides, while post treatment coproculture results showed that only H. contortus survived fenbendazole (FBZ) (in FECRT) or thiabendazole (TBZ) (in LDA) treatment except in three flocks of Tarai region {one sheep flock (Us1), and two goat flocks (Ug1 and Ug5)} where BZ resistant Trichostrongylus were also detected. The GIN of those eight farms which were found resistant by FECRT were also detected resistant by EHA. Arithmetic mean and range of ED50 value of susceptible group was found to be 0.059 μg/ml and 0.037-0.096 μg/ml, respectively, and the same for the resistant group were found to be 0.119 μg/ml and 0.101-0.147 μg/ml, respectively. With LDA, the arithmetic mean and range of LC50 value of susceptible group was found 0.0030 μg/ml and 0.001-0.005 μg/ml, respectively, and those of resistant group was found 0.0105 μg/ml and 0.009-0.012 μg/ml, respectively. The values of Spearman rank correlation coefficient indicated that negative correlation was found between FECR% and ED50 and between FECR% and LC50 while positive correlation existed between ED50 and LC50 value and the p-values indicated that these correlations were statistically highly significant. In the present study, FECRT and EHA gave comparable results with regard to detection of BZ resistance in GIN in sheep and goats. Although with LDA, the

  17. Synthesis and properties of a new red luminescence europium complex containing a 2-(benzimidazol-2-yl)-8-octyloxyquinoline as the second ligand. (United States)

    Li, Shanji


    A new Eu(III) complex, Eu(III)(DBM)(3) BIOQ, has been synthesized with dibenzoylmethane (DBM) as the first ligand and 2-(benzimidazol-2-yl)-8-octyloxyquinoline (BIOQ) as the second ligand. The stability of the complex was analysed by DSC-TG. The results show that the Eu(III) complex has a relatively high thermal stability with a melting point of 235 °C and a decomposition temperature (onset) of 252 °C. The fluorescence properties of the compound were also investigated. The fluorescence results reveal that the as-prepared complex shows the characteristic maximum emission spectra of Eu(III) at 611 nm (λ(ex) = 350 nm). In addition, the photoluminescence spectrum of the complex in the solid state exhibits a single and symmetrical emission band at 611 nm, with a full width at half-maximum of 4.7 nm, showing high colour purity. This finding indicates the possibility for the development of brighter red luminescent materials.

  18. Design and synthesis of cis-restricted benzimidazole and benzothiazole mimics of combretastatin A-4 as antimitotic agents with apoptosis inducing ability. (United States)

    Ashraf, Md; Shaik, Thokhir B; Malik, M Shaheer; Syed, Riyaz; Mallipeddi, Prema L; Vardhan, M V P S Vishnu; Kamal, Ahmed


    A series of colchicine site binding tubulin inhibitors were designed and synthesized by the modification of the combretastatin A-4 (CA4) pharmacophore. The ring B was replaced by the pharmacologically relevant benzimidazole or benzothiazole scaffolds, and the cis-configuration of the olefinic bond was restricted by the incorporation of a pyridine ring which is envisaged by the structural resemblance to a tubulin inhibitor like E7010. These compounds were evaluated for their antiproliferative activity on selected cancer cell lines and an insight in the structure activity relationship was developed. The most potent compounds (6c and 6l) demonstrated an antiproliferative effect comparable and superior to that of CA4 (GI50 up to 40nM). Mitotic cell cycle arrest in G2/M phase revealed the disruption of microtubule dynamics that was confirmed by tubulin polymerization assays and immunocytochemistry studies at the cellular level. The molecular docking studies suggested that the binding of these mimics at the colchicine site of the tubulin is similar to that of combretastatin A-4.

  19. Discovery and optimization of new benzimidazole- and benzoxazole-pyrimidone selective PI3Kβ inhibitors for the treatment of phosphatase and TENsin homologue (PTEN)-deficient cancers. (United States)

    Certal, Victor; Halley, Frank; Virone-Oddos, Angela; Delorme, Cécile; Karlsson, Andreas; Rak, Alexey; Thompson, Fabienne; Filoche-Rommé, Bruno; El-Ahmad, Youssef; Carry, Jean-Christophe; Abecassis, Pierre-Yves; Lejeune, Pascale; Vincent, Loic; Bonnevaux, Hélène; Nicolas, Jean-Paul; Bertrand, Thomas; Marquette, Jean-Pierre; Michot, Nadine; Benard, Tsiala; Below, Peter; Vade, Isabelle; Chatreaux, Fabienne; Lebourg, Gilles; Pilorge, Fabienne; Angouillant-Boniface, Odile; Louboutin, Audrey; Lengauer, Christoph; Schio, Laurent


    Most of the phosphoinositide-3 kinase (PI3K) kinase inhibitors currently in clinical trials for cancer treatment exhibit pan PI3K isoform profiles. Single PI3K isoforms differentially control tumorigenesis, and PI3Kβ has emerged as the isoform involved in the tumorigenicity of PTEN-deficient tumors. Herein we describe the discovery and optimization of a new series of benzimidazole- and benzoxazole-pyrimidones as small molecular mass PI3Kβ-selective inhibitors. Starting with compound 5 obtained from a one-pot reaction via a novel intermediate 1, medicinal chemistry optimization led to the discovery of compound 8, which showed a significant activity and selectivity for PI3Kβ and adequate in vitro pharmacokinetic properties. The X-ray costructure of compound 8 in PI3Kδ showed key interactions and structural features supporting the observed PI3Kβ isoform selectivity. Compound 8 achieved sustained target modulation and tumor growth delay at well tolerated doses when administered orally to SCID mice implanted with PTEN-deficient human tumor xenografts.

  20. Targeting the binding function 3 (BF3) site of the androgen receptor through virtual screening. 2. development of 2-((2-phenoxyethyl) thio)-1H-benzimidazole derivatives. (United States)

    Munuganti, Ravi Shashi Nayana; Leblanc, Eric; Axerio-Cilies, Peter; Labriere, Christophe; Frewin, Kate; Singh, Kriti; Hassona, Mohamed D H; Lack, Nathan A; Li, Huifang; Ban, Fuqiang; Tomlinson Guns, Emma; Young, Robert; Rennie, Paul S; Cherkasov, Artem


    The human androgen receptor (AR) is a proven therapeutic target in prostate cancer. All current antiandrogens, such as Bicalutamide, Flutamide, Nilutamide, and Enzalutamide, target the buried hydrophobic androgen binding pocket of this protein. However, effective resistance mechanisms against these therapeutics exist such as mutations occurring at the target site. To overcome these limitations, the surface pocket of the AR called binding function 3 (BF3) was characterized as an alternative target for small molecule therapeutics. A number of AR inhibitors directly targeting the BF3 were previously identified by us ( J. Med. Chem. 2011 . 54 , 8563 ). In the current study, based on the prior results, we have developed structure-activity relationships that allowed designing a series of 2-((2-phenoxyethyl)thio)-1H-benzimidazole and 2-((2-phenoxyethyl)thio)-1H-indole as lead BF3 inhibitors. Some of the developed BF3 ligands demonstrated significant antiandrogen potency against LNCaP and Enzalutamide-resistant prostate cancer cell lines.

  1. Synergism from combinations of tris(benzimidazole) monochloroplatinum(II) chloride with capsaicin, quercetin, curcumin and cisplatin in human ovarian cancer cell lines. (United States)

    Arzuman, Laila; Beale, Philip; Chan, Charles; Yu, Jun Q; Huq, Fazlul


    In the present study, synergism in activity from the sequenced combinations of monofunctional platinum tris(benzimidazole)monochloroplatinum(II) chloride (coded as LH4) with capsaicin, quercetin, curcumin and cisplatin was investigated as a function of sequence of administration in a number of human ovarian tumor models. Cellular accumulations of platinum and the levels of platinum-DNA binding were also determined for the 0/0 h and 4/0 sequences of administration. LH4 was found to be more active against the resistant A2780(cisR) and A2780(ZD0473R) cell lines than the parent A2780 cell line. As applied to combinations of LH4 with phytochemicals capsaicin, quercetin and curcumin, bolus administration was found to be most synergistic in both the parent A2780 and the resistant A2780(cisR) cell lines. For the combinations of LH4 with cisplatin, additiveness was observed in both the resistant cell lines but mild synergism was observed in the parent cell line. Greater activity of designed monofunctional platinum LH4 against resistant tumor models and synergism from combinations with phytochemicals indicate that the compound has the potential for development as a novel platinum-based anticancer drug.

  2. Synthesis and biological evaluation of imidazo[1,5-a]pyridine-benzimidazole hybrids as inhibitors of both tubulin polymerization and PI3K/Akt pathway. (United States)

    Kamal, Ahmed; Rao, A V Subba; Nayak, V Lakshma; Reddy, N V Subba; Swapna, Konderu; Ramakrishna, G; Alvala, Mallika


    A series of imidazo[1,5-a]pyridine-benzimidazole hybrids (5a–aa) were prepared and evaluated for their cytotoxic activity against a panel of sixty human tumor cell lines. Among them compounds 5d and 5l showed significant cytotoxic activity with GI50 values ranging from 1.06 to 14.9 μM and 0.43 to 7.73 μM, respectively. Flow cytometric analysis revealed that these compounds arrest the cell cycle at G2/M phase and induced cell death by apoptosis. The tubulin polymerization assay (IC50 of 5d is 3.25 μM and 5l is 1.71 μM) and immunofluorescence analysis showed that these compounds effectively inhibited the microtubule assembly in human breast cancer cells (MCF-7). Further, the apoptotic effects of compounds were confirmed by Hoechst staining, mitochondrial membrane potential, cytochrome c release, ROS generation, caspase 9 activation and DNA fragmentation analysis. After treatment with these compounds for 48 h, p-PTEN and p-AKT levels were markedly decreased. Moreover, these compounds did not significantly inhibit the normal human embryonic kidney cells, HEK-293. The molecular docking simulations predicted the binding interactions of 5d and 5l with colchicine binding site of the tubulin, which is in compliance with the antiproliferative activity data.

  3. Design, synthesis and biological evaluation of 1,3-diphenyl-1H-pyrazole derivatives containing benzimidazole skeleton as potential anticancer and apoptosis inducing agents. (United States)

    Reddy, T Srinivasa; Kulhari, Hitesh; Reddy, V Ganga; Bansal, Vipul; Kamal, Ahmed; Shukla, Ravi


    A series of forty different pyrazole containing benzimidazole hybrids (6-45) have been designed, synthesized and evaluated for their potential anti-proliferative activity against three human tumor cell lines - lung (A549), breast (MCF-7), and cervical (HeLa). Some of the compounds, specifically 9, 17, and 28, showed potent growth inhibition against all the cell lines tested, with IC50 values in the range of 0.83-1.81 μM. Breast cancer cells were used for further detailed studies to understand the mechanism of cell growth inhibition and apoptosis inducing effect of compounds. The morphology, cell migration and long term clonogenic survival of MCF-7 breast cancer cells were severely affected by treatment with these compounds. Flow-cytometry revealed the compounds arrested MCF-7 cells in the G1 phase of the cell cycle via down regulation of cyclin D2 and CDK2. Fluorescent staining and DNA fragmentation studies showed that cell proliferation was inhibited by induction of apoptosis. Moreover, the compounds led to collapse of mitochondrial membrane potential (DΨm) and increased levels of reactive oxygen species (ROS) were noted. The ease of synthesis and the remarkable biological activities make these compounds promising new frameworks for the development of cancer therapeutics.

  4. New dimeric carbazole-benzimidazole mixed ligands for the stabilization of human telomeric G-quadruplex DNA and as telomerase inhibitors. A remarkable influence of the spacer. (United States)

    Maji, Basudeb; Kumar, Krishan; Muniyappa, K; Bhattacharya, Santanu


    The development of G-quadruplex (G4) DNA binding small molecules has become an important strategy for selectively targeting cancer cells. Herein, we report the design and evolution of a new kind of carbazole-based benzimidazole dimers for their efficient telomerase inhibition activity. Spectroscopic titrations reveal the ligands high affinity toward the G4 DNA with significantly higher selectivity over duplex-DNA. The electrophoretic mobility shift assay shows that the ligands efficiently promote the formation of G4 DNA even at a lower concentration of the stabilizing K(+) ions. The TRAP-LIG assay demonstrates the ligand's potential telomerase inhibition activity and also establishes that the activity proceeds via G4 DNA stabilization. An efficient nuclear internalization of the ligands in several common cancer cells (HeLa, HT1080, and A549) also enabled differentiation between normal HFF cells in co-cultures of cancer and normal ones. The ligands induce significant apoptotic response and antiproliferative activity toward cancer cells selectively when compared to the normal cells.

  5. Antitumor activity of amidino-substituted benzimidazole and benzimidazo[1,2-a]quinoline derivatives tested in 2D and 3D cell culture systems. (United States)

    Brajša, Karmen; Vujasinović, Ines; Jelić, Dubravko; Trzun, Marija; Zlatar, Ivo; Karminski-Zamola, Grace; Hranjec, Marijana


    Due to a poor clinical predictive power of 2D cell cultures, standard tool for in vitro assays in drug discovery process, there is increasing interest in developing 3D in vitro cell cultures, biologically relevant assay feasible for the development of robust preclinical anti-cancer drug screening platforms. Herein, we tested amidino-substituted benzimidazoles and benzimidazo[1,2-a]quinolines as a small platform for comparison of antitumor activity in 2D and 3D cell culture systems and correlation with structure-activity relationship. 3D cell culture method was applied on a human cancer breast (SK-BR-3, MDA-MB-231, T-47D) and pancreatic cancer cells (MIA PaCa-2, PANC-1). Results obtained in 2D and 3D models were highly comparable, but in some cases we have observed significant disagreement indicating that some prominent compounds can be discarded in early phase of researching because of compounds with false positive result. To confirm which of cell culture systems is more accurate, in vivo profiling is needed.

  6. Design, synthesis and molecular modeling studies of few chalcone analogues of benzimidazole for epidermal growth factor receptor inhibitor in search of useful anticancer agent. (United States)

    Chhajed, Santosh S; Sonawane, Sandeep S; Upasani, Chandrashekhar D; Kshirsagar, Sanjay J; Gupta, Pramodkumar P


    In the present investigation, few 3-(substitutedphenyl)-1-[2-(1-hydroxy-ethyl)]-1H-benzimidazol-1-yl)prop-2-en-1-ones are EGFR antagonist are designed, by molecular docking analysis. The synthesized compounds were tested for their in vitro anticancer activity by propidium iodide fluorescent assay and Trypan blue viability assay against colorectal cancer cell lines (HCT116) and non-small cell lung cancer cell lines (H460). Human Epithelial Kidney cell lines (HEK) are used as normal cell lines for studying effect of drug on non-cancerous cells within human body. Evaluation of cytotoxic studies of synthesized compounds CHL(1-8) reveal that compound CHL1 [IC50=7.31 and 10.16 μM against HCT116 and H460 cell lines respectively, by PI assay] and CHL8 [IC50=12.52 and 6.83 against HCT116 and H460μM cell lines respectively] possess promising cytotoxic activity.

  7. Synthesis, molecular docking and biological evaluation of 1-phenylsulphonyl-2-(1-methylindol-3-yl)-benzimidazole derivatives as novel potential tubulin assembling inhibitors. (United States)

    Wang, Yan-Ting; Cai, Xun-Chao; Shi, Tian-Qi; Zhang, Ya-Liang; Wang, Zhong-Chang; Liu, Chang-Hong; Zhu, Hai-Liang


    A series of new 1-phenylsulphonyl-2-(1-methylindol-3-yl)-benzimidazole derivatives were designed, synthesized and evaluated as potential inhibitors of tubulin polymerization and anthropic cancer cell lines. Among them, compound 33 displayed the most potent tubulin polymerization inhibitory activity in vitro (IC50  = 1.41 μM) and strong antiproliferative activities against A549, Hela, HepG2 and MCF-7 cell lines in vitro with GI50 value of 1.6, 2.7, 2.9 and 4.3 μM, respectively, comparable with the positive control colchicine (GI50 value of 4.1, 7.2, 9.5 and 14.5 μM, respectively) and CA-4 (GI50 value of 2.2, 4.3, 6.4 and 11.4 μM, respectively). Simultaneously, we evaluated that compound 33 could effectively induce apoptosis of A549 associated with G2/M phase cell cycle arrest. Immunofluorescence microscopy also clearly indicated compound 33 a potent antimicrotubule agent. Docking simulation showed that compound 33 could bind tightly with the colchicine-binding site and act as a tubulin inhibitor. Three-dimensional-QSAR model was also built to provide more pharmacophore understanding that could be used to design new agents with more potent tubulin assembling inhibitory activity in the future.

  8. Fac-mer equilibria of coordinated iminodiacetate (ida2-) in ternary CuII(ida)(H-1B)- complex formation (B = imidazole, benzimidazole) in aqueous solution

    Indian Academy of Sciences (India)

    Susmita Bandyopadhyay; G N Mukherjee


    pH potentiometric and spectrophotometric investigations on the complex formation equilibria of CuII with iminodiacetate (ida2-) and heterocyclic N-bases, viz. imidazole and benzimidazole (B), in aqueous solution in binary and ternary systems using different molar ratios of the reactants indicated the formation of complexes of the types, Cu(ida), Cu(ida)(OH)-, (ida)Cu(OH)Cu(ida)-, Cu(B)2+, Cu(H-1B)+, Cu(ida)(H-1B)-, (ida)Cu(B)Cu(ida) and (ida)Cu(H-1B)Cu(ida)-. Formation constants of the complexes at 25 ± 1° at a fixed ionic strength, = 0.1 mol dm-3 (NaNO3) in aqueous solution were evaluated and the complex formation equilibria were elucidated with the aid of speciation curves. Departure of the experimental values of the reproportionation constants (log Cu) of ternary Cu(ida)(H-1B)- complexes from the statistically expected values, despite their formation in appreciable amounts at equilibrium, were assigned to fac(f)-mer(m) equilibria of the ida2- ligand coordinated to CuII, as the N-heterocyclic donors, (H-1B)-, coordinate trans- to the N-(ida2-) atom in the binary Cu(ida) complex to form the ternary Cu(ida) (H-1B)- complexes.

  9. Synthesis,Structure and Luminescence of Two Coordination Polymers Based on 1,4-Benzenedicarboxylate and 2-(3-Pyridyl)benzimidazole Ligands

    Institute of Scientific and Technical Information of China (English)

    LI wei; LI Ming-Xing; HE Xiang; SHAO Min; AN Bao-Li


    Hydrothermal reactions of Cd(Ⅱ)/Zn(Ⅱ)nitrates with 1,4-benzenedicarboxylic acid(H2Bdc)and 2-(3-pyridyl)-benzimidazole(3-PyHBIm)afforded complexes {[Cd(3-PyHBlm)(Bdc)(H2O)2](H2Bdc)1/2]n(1)and [Zn(3-PyHBIm)2-(Bdc)(H2O)2]n(2).X-ray structural analysis reveals that both complexes are ID coordination polymers.In complex 1,3-PyHBIm coordinates to Cd(Ⅱ)unidentately via a pyridyl N-donor.Bdc2-anion acts as a tetradentate ligand and coordinates to Cd(Ⅱ)to form a zigzag chain where two H2O coordinate in cis-fashion.H2Bdc guest molecule is involved in the hydrogen-bonding network,which leads to a 3D supramolecular architecture.In complex 2,Bdc2-acts as a bidentate ligand and coordinates to Zn(Ⅱ)to form a linear infinite chain where two H2O molecules coordi-nate in trans-fashion.The complexes are thermally stable and exhibit luminescence in the solid state.

  10. A new ternary copper(II) complex derived from 2-(2'-pyridyl)benzimidazole and glycylglycine: synthesis, characterization, DNA binding and cleavage, antioxidation and HSA interaction. (United States)

    Fu, Xia-Bing; Lin, Zi-Hua; Liu, Hai-Feng; Le, Xue-Yi


    A new ternary copper(II)-dipeptide complex [Cu(glygly)(HPB)(Cl)]⋅2H2O (glygly=glycylglycine anion, HPB=2-(2'-pyridyl)benzimidazole) has been synthesized and characterized. The DNA interaction of the complex was studied by spectroscopic methods, viscosity, and electrophoresis measurements. The antioxidant activity was also investigated using the pyrogallol autoxidation assay. Besides, the interaction of the complex with human serum albumin (HSA) in vitro was examined by multispectroscopic techniques. The complex partially intercalated to CT-DNA with a high binding constant (Kb=7.28×10(5) M(-1)), and cleaved pBR322 DNA efficiently via an oxidative mechanism in the presence of Vc, with the HO· and O2(-) as the active species, and the SOD as a promoter. Furthermore, the complex shows a considerable SOD-like activity with the IC50 value of 3.8386 μM. The complex exhibits desired binding affinity to HSA, in which hydrogen bond or vander Waals force played a major role. The alterations of HSA secondary structure induced by the complex were confirmed by UV-visible, CD, synchronous fluorescence and 3D fluorescence spectroscopy.

  11. A study (1977-1992) of population dynamics of endoparasites featuring benzimidazole-resistant small strongyles (population S) in Shetland ponies. (United States)

    Lyons, E T; Tolliver, S C; Drudge, J H; Stamper, S; Swerczek, T W; Granstrom, D E


    Critical tests (91) were done between 1977 and 1992 in Shetland ponies to evaluate drug susceptibility and population dynamics (present paper) of endoparasites. The test ponies, most less than 1 year old, were from a herd where older animals were treated every 8 weeks initially with cambendazole (CBZ) (1974-1978) and then with oxibendazole (OBZ) (1978-1992). Previous field test data (1974-1992) on older ponies in the breeding herd indicated the presence of benzimidazole (BZ) resistant small strongyles. Data on population dynamics from the present critical tests indicated that 28 species of small strongyles persisted over the study period in spite of initial susceptibility and later refractiveness of six species to both CBZ and OBZ. Changes in intensities and other aspects were observed for the six BZ-resistant species (Cyathostomum catinatium, Cyathostomum coronatum, Cylicocyclus nassatus, Cylicostephanus calicatus, Cylicostephanus goldi, and Cylicostephanus longibursatus). Variabilities, some striking, were found in prevalence and intensity in bots, stomach worms, ascarids, eyeworms, large strongyles, pinworms and tapeworms.

  12. Selective and eco-friendly procedures for the synthesis of benzimidazole derivatives. The role of the Er(OTf3 catalyst in the reaction selectivity

    Directory of Open Access Journals (Sweden)

    Natividad Herrera Cano


    Full Text Available An improved and greener protocol for the synthesis of benzimidazole derivatives, starting from o-phenylenediamine, with different aldehydes is reported. Double-condensation products were selectively obtained when Er(OTf3 was used as the catalyst in the presence of electron-rich aldehydes. Conversely, the formation of mono-condensation products was the preferred path in absence of this catalyst. One of the major advantages of these reactions was the formation of a single product, avoiding extensive isolation and purification of products, which is frequently associated with these reactions.Theoretical calculations helped to understand the different reactivity established for these reactions. Thus, we found that the charge density on the oxygen of the carbonyl group has a significant impact on the reaction pathway. For instance, electron-rich aldehydes better coordinate to the catalyst, which favours the addition of the amine group to the carbonyl group, therefore facilitating the formation of double-condensation products.Reactions with aliphatic or aromatic aldehydes were possible, without using organic solvents and in a one-pot procedure with short reaction time (2–5 min, affording single products in excellent yields (75–99%. This convenient and eco-friendly methodology offers numerous benefits with respect to other protocols reported for similar compounds.

  13. A mutant beta-tubulin confers resistance to the action of benzimidazole-carbamate microtubule inhibitors both in vivo and in vitro. (United States)

    Foster, K E; Burland, T G; Gull, K


    The mutant BEN210 of Physarum polycephalum is highly resistant to a number of benzimidazole carbamate agents, including methylbenzimidazole-2-yl-carbamate and parbendazole. The resistance is conferred by the benD210 mutation in a structural gene for beta-tubulin. This mutant allele encodes a beta-tubulin with novel electrophoretic mobility. We have used this strain to determine whether the mutant beta-tubulin is used in microtubules and whether this usage permits microtubule polymerisation in the presence of drugs both in vivo and in vitro. In vitro assembly studies of tubulin purified from the mutant strain have shown that microtubules are formed both in the absence of drugs and in all drug concentrations tested (up to 50 microM parbendazole). In contrast, the assembly of microtubules from wild-type tubulin in vitro is totally inhibited by 2-5 microM parbendazole. Thus the resistance of BEN210 to parbendazole observed in vivo has been reproduced in vitro using tubulin purified from the mutant strain. Electrophoretic analysis of the microtubules formed in vitro has shown that both the wild-type and the mutant beta-tubulin are incorporated into the microtubules and that the proportion of mutant to wild-type beta-tubulin appears to remain constant with increasing drug concentration. This is the first demonstration of a single mutation in a tubulin structural gene causing an altered function of the gene product in vitro.

  14. Design and Characterization of Heteroleptic Ruthenium Complexes Containing Benzimidazole Ligands for Dye-Sensitized Solar Cells: The Effect of Fluorine Substituents on Photovoltaic Performance. (United States)

    Huang, Wei-Kai; Wu, Hui-Ping; Lin, Pi-Lun; Lee, Yuan-Pern; Diau, Eric Wei-Guang


    We designed heteroleptic ruthenium complexes (RD12-RD15) containing fluoro-substituted benzimidazole ligands for dye-sensitized solar cells (DSSCs). These dyes were synthesized according to a typical one-pot procedure with the corresponding ancillary ligands produced in two simple steps; they were prepared into DSSC devices according to the same conditions of fabrication. The eventual devices show a systematic trend of increasing VOC and decreasing JSC with fluorine atoms of increasing number substituted on the ligand. The charge-extraction results show that upward shifts of the TiO2 potential occurred when the fluoro-substituted dyes were sensitized on TiO2 with a systematic trend of shift N719 > RD15 (with 5 F) > RD12 (with 2 F) >RD5 (no F); the intensity-modulated photovoltage spectra indicate that those fluoro substituents retard charge recombination with the electron lifetimes (τR) in the order RD15 > RD12 > RD5 > N719, consistent with the variation of VOC for the systems.

  15. Discovery, SAR, and Radiolabeling of Halogenated Benzimidazole Carboxamide Antagonists as Useful Tools for (alpha)4(beta)1 Integrin Expressed on T- and B-cell Lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, R D; Natarajan, A; Lau, E Y; Andrei, M; Solano, D M; Lightstone, F C; DeNardo, S J; Lam, K S; Kurth, M J


    The cell surface receptor {alpha}{sub 4}{beta}{sub 1} integrin is an attractive yet poorly understood target for selective diagnosis and treatment of T- and B-cell lymphomas. This report focuses on the rapid microwave preparation of medicinally pertinent benzimidazole heterocycles, structure-activity relationships (SAR) of novel halobenzimidazole carboxamide antagonists 3-6, and preliminary biological evaluation of radioiodinated agents 7, 8, and 18. The I-125 derivative 18 had good tumor uptake (12 {+-} 1% ID/g at 24 h; 4.5 {+-} 1% ID/g at 48 h) and tumor:kidney ratio ({approx}4:1 at 24 h; 2.5:1 at 48 h) in xenograft murine models of B-cell lymphoma. Molecular homology models of {alpha}{sub 4}{beta}{sub 1} integrin have predicted that docked halobenzimidazole carboxamides have the halogen atom in a suitable orientation for halogen-hydrogen bonding. These high affinity ({approx} pM binding) halogenated ligands are attractive tools for medicinal and biological use; the fluoro and iodo derivatives are potential radiodiagnostic ({sup 18}F) or radiotherapeutic ({sup 131}I) agents, whereas the chloro and bromo analogues could provide structural insight into integrin-ligand interactions through photoaffinity cross-linking/mass spectroscopy experiments, as well as co-crystallization X-ray studies.

  16. A novel benzimidazole-functionalized 2-D COF material: synthesis and application as a selective solid-phase extractant for separation of uranium. (United States)

    Li, Juan; Yang, Xiaodan; Bai, Chiyao; Tian, Yin; Li, Bo; Zhang, Shuang; Yang, Xiaoyu; Ding, Songdong; Xia, Chuanqin; Tan, Xinyu; Ma, Lijian; Li, Shoujian


    A novel COF-based material (COF-COOH) containing large amounts of carboxylic groups was prepared for the first time by using a simple and effective one-step synthetic method, in which the cheap and commercially available raw materials, trimesoyl chloride and p-phenylenediamine, were used. The as-synthesized COF-COOH was modified with previously synthesized 2-(2,4-dihydroxyphenyl)-benzimidazole (HBI) by "grafting to" method, and a new solid-phase extractant (COF-HBI) with highly efficient sorption performance for uranium(VI) was consequently obtained. A series of characterizations demonstrated that COF-COOH and COF-HBI exhibited great thermostabilities and irradiation stabilities. Sorption behavior of the COF-based materials toward U(VI) was compared in simulated nuclear industrial effluent containing UO2(2+) and 11 undesired ions, and the UO2(2+) sorption amount of COF-HBI was 81 mg g(-1), accounting for approximately 58% of the total sorption amount, which was much higher than the sorption selectivity of COF-COOH to UO2(2+) (39%). Batch sorption experiment results indicated that the uranium(VI) sorption on COF-HBI was a pH dependent, rapid (sorption equilibrium was reached in 30 min), endothermic and spontaneous process. In the most favorable conditions, the equilibrium sorption capacity of the adsorbent for uranium could reach 211 mg g(-1).

  17. Análise genética de isolados do Haemonchus sp de ruminantes domésticos para identificação da resistência ao anti-helmíntico Benzimidazol


    Ronaldo Luiz Nunes


    O objetivo deste trabalho é caracterizar geneticamente a resistência ao anti-helmíntico benzimidazol (BZ) em helmintos Haemonchus sp isolados de ruminantes. Para tanto trinta animais pertencentes a um rebanho de bovinos, um rebanho de Caprinos, um rebanho de Ovinos e um rebanho de Bubalinos, tiveram amostras de fezes coletadas e analisadas para a presença de ovos de Tricostrongilídeos. As propriedades foram avaliadas quanto ao histórico de uso de BZ para controle de nematódeos. Nos rebanhos b...

  18. Aqua(1H-benzimidazole-κN3(pyridine-2,6-dicarboxylato-κ3O2,N,O6copper(II 0.75-hydrate

    Directory of Open Access Journals (Sweden)

    Gui-Ying Dong


    Full Text Available The title complex, [Cu(C7H3NO4(C7H6N2(H2O]·0.75H2O, consists of discrete monomeric units. The CuII atom is coordinated by two carboxylate O atoms and the N atom from a dipicolinate unit and by an N atom from a benzimidazole ligand. The distorted square-pyramidal geometry is completed by a longer axial bond to the O atom of a water molecule. The molecular structure and packing are stabilized by classical O—H...O and N—H...O hydrogen bonds, also including a disordered crystal water molecule.

  19. PTA (H3PO4·12WO3·xH2O: An eco-friendly catalyst for the synthesis of new Schiff-bases containing benzimidazole moiety

    Directory of Open Access Journals (Sweden)

    Varsha U. Vernekar


    Full Text Available In this study H3PO4·12WO3·xH2O is found to catalyze the preparation of Schiff bases from the reaction of 3-(1H-Benzimidazol-2-ylnaphthalene-2-amine with different aldehydes efficiently in ethanol. The advantages of this environmental friendly and mild method are such as simplicity of the reaction procedure, the elimination of solvents, simple work-up, high product yields and short reaction times. The products were characterized by FT-IR 1H NMR, 13C NMR, mass spectrometry and elemental analysis.

  20. Rapid 'one-pot' synthesis of a novel benzimidazole-5-carboxylate and its hydrazone derivatives as potential anti-inflammatory and antimicrobial agents. (United States)

    Vasantha, Kumar; Basavarajaswamy, Guru; Vaishali Rai, M; Boja, Poojary; Pai, Vinitha R; Shruthi, N; Bhat, Mahima


    A novel series of N-arylidene-2-(2,4-dichloro phenyl)-1-propyl-1H-benzo[d] imidazole-5-carbohydrazides having different substitution on the arylidene part were synthesized in good yield. The core nucleus benzimidazole-5-carboxylate (5) was efficiently synthesized by 'one-pot' nitro reductive cyclization reaction between ethyl-3-nitro-4-(propylamino)benzoate and 2,4-dichlorobenzaldehyde using sodium dithionite in dimethylsulfoxide. This 'one-pot' reaction was proceeded very smoothly, in short reaction time with an excellent yield. All the compounds (7a-r) were screened for their in vivo anti-inflammatory and in vitro antimicrobial activity. Most of the compounds exhibited remarkable paw-edema inhibition in the initial one hour of administration indicating the higher potentiality of these molecules. In particular, compounds 7a, 7d, 7f and 7g displayed a high level of carrageenan-induced paw edema inhibition compared to that of indomethacin. Compound 7p exhibited very good antibacterial activity and antifungal activity with a MIC of 3.12 μg/mL against most of the tested organisms. Furthermore, compounds 7d, 7f, 7h and 7p found to be good inhibitors of Aspergillus niger with MIC of 3.12 μg/mL. Cytotoxicity of the potent compounds 7d, 7f and 7p was checked using MDA MB-231 breast cancer cell line and are found to be non toxic at the highest concentration used (i.e., 10 μg/mL).

  1. Phenotypic and genotypic characterisation of Haemonchus spp. and other gastrointestinal nematodes resistant to benzimidazole in infected calves from the tropical regions of Campeche State, Mexico. (United States)

    Encalada-Mena, Lisandro; Tuyub-Solis, Henry; Ramirez-Vargas, Gabriel; Mendoza-de-Gives, Pedro; Aguilar-Marcelino, Liliana; López-Arellano, Ma Eugenia


    The aim of this study was to identify the presence of anthelmintic resistance to benzimidazole (BZ) in gastrointestinal nematodes (GIN) from naturally infected calves in the tropical regions of Campeche State of Mexico. The faecal egg count reduction test (FECRT) was conducted at 10 livestock farms localised in the Carmen, Candelaria, Champotón, Escárcega and Palizada municipalities of Campeche. The assessed anthelmintic was albendazole. The trial period was between August and November 2012. Infected calves were allocated into two groups, control and treated, on each farm. The number of eggs excreted per g of faeces was estimated by the McMaster technique at 0 and 14 days pre- and post- treatment, respectively. Recovered infective larvae (L3) (pre- and post-treatment) were identified using taxonomic keys and a genomic DNA (gDNA) template from a pool of L3 species prior to BZ treatment. Additionally, BZ-resistance polymorphisms in Haemonchus were determined by Allele Specific PCR (AS-PCR) at codon 200 and by end-point PCR at codons 200, 198 and 167 from isotype 1 of the β-tubulin gene. Morphological identification revealed Haemonchus, Cooperia, Trichostrongylus, Ostertagia and Oesophagostumum L3 species before BZ treatment, and Haemonchus and Cooperia L3 species after treatment. Additionally, of the GIN populations, three exhibited BZ resistance, and seven were BZ-susceptible by FECRT. Molecular analysis identified mutations in Haemonchus populations on nine farms at codon 200 (TTC to TAC) by AS-PCR, while no changes were observed at 167 (TTC to TAC) or 198 (GAA to GCA) codons in any population. In conclusion, resistance to BZ was determined in Haemonchus and Cooperia nematodes in infected cattle in five tropical regions of Campeche State.

  2. Two benzimidazole resistance-associated SNPs in the isotype-1 β-tubulin gene predominate in Haemonchus contortus populations from eight regions in China

    Directory of Open Access Journals (Sweden)

    Zongze Zhang


    Full Text Available Haemonchus contortus is one of the most important parasitic nematodes of small ruminants around the world, particularly in tropical and subtropical regions. The control of haemonchosis relies mainly on anthelmintics, but the excessive and prolonged use of anthelmintics is causing serious drug resistance issues in many countries. As benzimidazole (BZ anthelmintics have been broadly used in China, we hypothesized that resistance is widespread. Given the link between three known single nucleotide polymorphisms (SNPs, designated F167Y, E198A and F200Y in the isotype-1 β-tubulin gene and BZ resistance, our goal here was to explore the presence of these mutations in H. contortus from small ruminants (sheep and goats from eight provinces in China using PCR-coupled sequencing. In addition, the genetic diversity and genetic relationship of isotype-1 β-tubulin sequence haplotypes were also investigated. Among 192 H. contortus adult individuals representing the eight populations, we identified six distinct sequence types, five of which had SNP E198A (GCA and/or F200Y (TAC. Sequence analysis showed that the frequencies of SNPs E198A and F200Y were 0–70% and 0–31%, respectively. SNP F167Y (TAC was not detected in any population. In addition, high haplotype diversities (0.455–0.939 and nucleotide diversities (0.018–0.039 were calculated. A network analysis of the isotype-1 β-tubulin gene sequences showed that SNPs E198A and F200Y occurred in multiple distinct groupings, suggesting multiple independent origins of these SNPs. The findings of this first study of SNPs in the isotype-1 β-tubulin gene of H. contortus populations suggest that BZ resistance is prevalent in some regions of China, and that any control strategy might focus on monitoring BZ resistance in this country.

  3. Effect of acid-catalyzed formation rates of benzimidazole-linked polymers on porosity and selective CO2 capture from gas mixtures. (United States)

    Altarawneh, Suha; İslamoğlu, Timur; Sekizkardes, Ali Kemal; El-Kaderi, Hani M


    Benzimidazole-linked polymers (BILPs) are emerging candidates for gas storage and separation applications; however, their current synthetic methods offer limited control over textural properties which are vital for their multifaceted use. In this study, we investigate the impact of acid-catalyzed formation rates of the imidazole units on the porosity levels of BILPs and subsequent effects on CO2 and CH4 binding affinities and selective uptake of CO2 over CH4 and N2. Treatment of 3,3'-Diaminobenzidine tetrahydrochloride hydrate with 1,2,4,5-tetrakis(4-formylphenyl)benzene and 1,3,5-(4-formylphenyl)-benzene in anhydrous DMF afforded porous BILP-15 (448 m(2) g(-1)) and BILP-16 (435 m(2) g(-1)), respectively. Alternatively, the same polymers were prepared from the neutral 3,3'-Diaminobenzidine and catalytic amounts of aqueous HCl. The resulting polymers denoted BILP-15(AC) and BILP-16(AC) exhibited optimal surface areas; 862 m(2) g(-1) and 643 m(2) g(-1), respectively, only when 2 equiv of HCl (0.22 M) was used. In contrast, the CO2 binding affinity (Qst) dropped from 33.0 to 28.9 kJ mol(-1) for BILP-15 and from 32.0 to 31.6 kJ mol(-1) for BILP-16. According to initial slope calculations at 273 K/298 K, a notable change in CO2/N2 selectivity was observed for BILP-15(AC) (61/50) compared to BILP-15 (83/63). Similarly, ideal adsorbed solution theory (IAST) calculations also show the higher specific surface area of BILP-15(AC) and BILP-16(AC) compromises their CO2/N2 selectivity.

  4. Synthesis and Structural Studies on Transition Metal Complexes Derived from 4-Hydroxy-4-methyl–2-pentanone-1H-benzimidazol-2-yl-hydrazone

    Directory of Open Access Journals (Sweden)

    M. Neelamma


    Full Text Available Transition metal complexes of Cr(III, Fe(III, Mn(II, Co(II, Ni(II, Cu(II and Zn(II with a tridentate ligand, 4-hydroxy-4-methyl-2-pentanone-1H-benzimidazole-2yl-hydrazone (H-HPBH derived from the condensation of 2-hydrazinobenzimidazole and diacetone alcohol was synthesized. Characterization has been done on the basis of analytical, conductance, thermal and magnetic data, infrared, 1H NMR, electronic, mass and ESR spectral data. From analytical and thermal data, the stoichiometry of the complexes has been found to be 1:1 (metal: ligand. Divalent complexes have the general formula [M(HPBHCl(H2O2] in octahedral geometry, [M(HPBHCl] in tetrahedral and square planar stereochemistries and trivalent complexes [M(HPBHCl2(H2O] in octahedral disposition. Infrared spectral data suggest that the ligand HPBH behaves as a monobasic tridentate ligand with N: N: O donor sequence towards the metal ions. On the basis of the above physicochemical data, octahedral, tetrahedral and square planar geometries were assigned for the complexes. The ligand and metal complexes were screened for their physiological activities against E. coli and S. aureus. The order of physiological activity has been found to be Cu(II > Ni(II > Zn(II > Co(II > Cr(III > Mn(II > Fe (III > ligand against E.coli and Ni(II > Cu(II > Zn(II > Mn(II > Cr(III > Fe(III > Co(II > ligand against S. aureus.

  5. Treatment of fish parasites. 11. Effects of different benzimidazole derivatives (albendazole, mebendazole, fenbendazole) on Glugea anomala, Moniez, 1887 (Microsporidia): ultrastructural aspects and efficacy studies. (United States)

    Schmahl, G; Benini, J


    Three different benzimidazole derivatives, albendazole [methyl-5-(propylthio)-2-benzimidazolcarbamate], mebendazole (methyl-5-benzoyl-2-benzimidazolcarbamatic acid methyl ester), and fenbendazole [methyl-5-(phenylthio)-2-benzimidazolcarbamate] were tested in vivo against Glugea anomala parasitizing the connective tissue of sticklebacks (Gasterosteus aculeatus). Naturally infected sticklebacks were incubated in aerated plastic aquaria (10 1) at 22 degrees C in water containing 0, 1, 5, 10, or 50 micrograms of either albendazole, mebendazole or febendazole for 2 or 6 h. For intermittent treatment, 2 micrograms substance was administered three times for 6 h at intervals of 36 h. At the ultrastructural level, at all developmental stages of G. anomala there were no significant differences in the kind of damage caused by either albendazole, mebendazole, or febendazole. Starting with a dose of 1 microgram/ml for 2 h, each of the drugs irreversibly damaged uni- and multinucleate meronts, sporogonial plasmodia, and sporoblasts. Disorganized spores were also observed. Treatment with higher doses (10 micrograms/ml, 2 or 6 h) caused malformations of the merogonic and the sporogonic stages, a significant reduction in the number of ribosomes, and disruptions of the nuclear membranes. The first recognizable treatment effect was an enlargement of the smooth endoplasmic reticulum. In the sporogonial plasmodia, the membranes of the sporophorous vesicle envelopes were lumpy or even completely destroyed. After incubation with the highest dose (50 micrograms/ml, 6 h), microtubules were apparent within the karyoplasm of the uninucleate meronts. After interval treatment, all forms of damage were intensified, especially in the mature spores. When treatment was done three times at low doses (3 x 2 micrograms/ml, 6 h, 36-h intervals), spore infectivity was drastically lowered. Therefore, it seems likely that an intermittent regimen of medicinal baths can be successfully applied against

  6. Experimental infection of Haemonchus contortus strains resistant and susceptible to benzimidazoles and the effect on mast cells distribution in the stomach of Mongolian gerbils (Meriones unguiculatus). (United States)

    Königová, Alzbeta; Hrckova, Gabriela; Velebný, Samuel; Corba, Július; Várady, Marián


    Establishment rate of Haemonchus contortus in non-suppressed and immunosuppressed gerbils within 14 days post-infection was compared after inoculation with 1,000 third-stage larvae (L3), exsheathed BZ-susceptible larvae. Based on significantly higher number of larvae in gerbils receiving low doses of immunosuppressant agent hydrocortisone, development of benzimidazole (BZ)-susceptible and BZ-resistant strain of nematode in the stomach was studied on days 4, 7, 10, and 14 p.i. Sections of stomach from both groups of animals were examined for overall histopathological response and dynamics of mucosal mast cells (MMC) and connective tissue mast cells (CTMC). In the immunosuppressed gerbils, H. contortus L3 stage larvae developed to the L4 stage on days 10 and 14 p.i., and their sex ratio was higher toward female worms. Significantly higher ratios of establishment rate were recorded for BZ-susceptible than BZ-resistant strain. Infection elicited strong inflammation mainly in the lamina propria mucosae, where MMC numbers peaked on day 7 p.i., being present in a significantly higher numbers in gerbils infected with BZ-susceptible strain. Infection with BZ-susceptible strain of nematode also resulted in a higher number of CTMC in comparison with the effect of BZ-resistant strain, which were observed in the tela submucosa only. Thus, H. contortus infection in gerbils seems to be a suitable model to study host-parasite interactions. Our results indicate that BZ-resistant strain of H. contortus have a decreased capacity to establish infection in direct relation with lower mucosal and connective tissue MCs counts in the stomach.

  7. Enhancing excited state intramolecular proton transfer in 2-(2'-hydroxyphenyl)benzimidazole and its nitrogen-substituted analogues by β-cyclodextrin: the effect of nitrogen substitution. (United States)

    Chipem, Francis A S; Behera, Santosh Kumar; Krishnamoorthy, G


    Excited state intramolecular proton transfer (ESIPT) in nitrogen-substituted analogues of 2-(2'-hydroxyphenyl)benzimidazole (HPBI), 2-(2'-hydroxyphenyl)-3H-imidazo[4,5-b]pyridine (HPIP-b), and 2-(2'-hydroxyphenyl)-3H-imidazo[4,5-c]pyridine (HPIP-c) have been investigated in a β-cyclodextrin (β-CD) nanocavity and compared with that of HPBI. The stoichiometry and the binding constants of the complexes were determined by tautomer emissions. Both pKa and NMR experiments were employed to determine the orientation of the molecules inside of the β-CD cavity. Huge enhancement in the tautomer emission of HPIP-b and HPIP-c compared to that of HPBI in β-CD suggests that not only is the ESIPT favored inside of the cavity, but also, the environment reduces the nonradiative decay through the formation of an intramolecular charge-transfer (ICT) state. Unlike HPBI, the tautomer emission to normal emission ratio of HPIP-b increases from 0.9 to 2.6, and that of HPIP-c increases from 4.9 to 7.4 in 15 mM β-CD. The effect of dimethylsulfoxide (DMSO) on complexation was also investigated for all three guest molecules. In DMSO, HPBI is present in neutral form, but the nitrogen-substituted analogues are present in both neutral and monoanionic forms. However, in DMSO upon encapsulation by β-CD, all three molecules are present in both neutral and monoanionic forms in the nanocavity. The monoanion is stabilized more inside of the β-CD cavity. The studies revealed that the ESIPT of nitrogen-substituted analogues is more susceptible to the environment than HPBI, and therefore, they are more promising probes.

  8. Antibacterial Activity and Cytotoxicity of Silver(I) Complexes of Pyridine and (Benz)Imidazole Derivatives. X-ray Crystal Structure of [Ag(2,6-di(CH2OH)py)2]NO3. (United States)

    Kalinowska-Lis, Urszula; Felczak, Aleksandra; Chęcińska, Lilianna; Szabłowska-Gadomska, Ilona; Patyna, Emila; Małecki, Maciej; Lisowska, Katarzyna; Ochocki, Justyn


    Selected aspects of the biological activity of a series of six nitrate silver(I) complexes with pyridine and (benz)imidazole derivatives were investigated. The present study evaluated the antibacterial activities of the complexes against three Gram-negative strains: Pseudomonas aeruginosa ATCC 15442, Escherichia coli ATCC 25922 and Proteus hauseri ATCC 13315. The results were compared with those of silver nitrate, a silver sulfadiazine drug and appropriate ligands. The most significant antibacterial properties were exerted by silver(I) complexes containing benzimidazole derivatives. The cytotoxic activity of the complexes was examined against B16 (murine melanoma) and 10T1/2 (murine fibroblasts) cells. All of the tested silver(I) compounds were not toxic to fibroblast cells in concentration inhibited cancer cell (B16) viability by 50%, which ranged between 2.44-28.65 µM. The molecular and crystal structure of silver(I) complex of 2,6-di(hydroxymethyl)pyridine was determined by single-crystal X-ray diffraction analysis. The most important features of the crystal packing and intermolecular non-covalent interactions in the Ag(I) complex were quantified via Hirshfeld surface analysis.

  9. 苯并咪唑类缓蚀剂缓蚀机理以及研究趋势%Corrosion-inhibiting mechanism and research tendency of the benzimidazole corrosion inhibitor

    Institute of Scientific and Technical Information of China (English)



    Benzimidazole corrosion inhibitor was a kind of hydrochloride pickling inhibitor. It was possessed various inhibition efficiency because of the distinction of substitutional group. It was occupied the characteristics of high performance,low mammalian toxicity and biodegradation. It also was a kind of adsorption corrosion inhibitor, it also was involved many aspects of resistance chemical corrosion, molecular interface adsorption, the groups covering effects as well as hydrogen-bonding association effects. It was analysised and introduced the preparation method, corrosion-inhibiting mechanism and research tendency of the benzimidazole corrosion inhibitor in this article.%苯并咪唑类缓蚀剂是一类盐酸酸洗缓蚀剂,当取代基不同,其分子呈现不同的缓蚀效率。苯并咪唑类缓蚀剂具有高效、低毒和生物易降解等特点。苯并咪唑缓蚀剂是吸附型缓蚀剂,它涉及到阻化效应、分子界面吸附、基团覆盖效应和氢键缔合效应等多方面。文中介绍了苯并咪唑类缓蚀剂的制备方式、缓释机理以及发展状况。

  10. Présence en Tunisie d'isolats de Fusarium sambucinum résistants aux benzimidazoles : développement in vitro et agressivité sur tubercules de pomme de terre

    Directory of Open Access Journals (Sweden)

    El Mahjoub M.


    Full Text Available Presence in Tunisia of Fusarium sambucinum isolates resistant to benzimidazoles: in vitro growth and aggressiveness on potato tubers. The behaviour of 55 isolates of Fusarium spp. causing dry rot of the potato tubers, is studied against some enzimidazoles fungicides. Tunisian isolates of F. solani (12, F. oxysporum (23 and F. graminearum (10 are sensitive in vitro to carbendazime and benomyl at 5 mg.l-1. Their interaction with thiophanate-methyl is different; a complete inhibition of their mycelial growth is observed at doses higher than 500 mg.l-1. Tunisian isolates of F. sambucinum collected during 2002, 2003 and 2004 are resistant to these benzimidazoles showing existence of a cross-resistance. In fact, these isolates tolerated carbendazime (and benomyl at 200 mg.l-1 and thiophanate-methyl at 1000 mg.l-1. This is the first study in Tunisia indicating emergence of this type of F. sambucinum resistance. Control isolates of F. sambucinum and those treated with carbendazime at 100 mg.l-1 showed a similar aggressiveness on potato tubers of the Spunta cultivar.

  11. [Synthesis of stable solvates of monosodium 2-[R*s,9S*)-(4-methoxy-6,7,8, 9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl)sulfinyl]-1H-benzimidazole]. (United States)

    Yamada, S; Goto, T; Yuasa, S; Yamaguchi, T; Kogi, K


    Monosodium 2-[(R*s,9S*)-(4-methoxy-6,7,8, 9-tetrahydro-5H-cyclohepta-[b]pyridin-9-yl)sulfinyl]-1H-benzimidazole (3A), a novel antiulcer agent previously reported by us, was found to be easily decomposed in weakly acidic solutions. In order to improve the stability of the parent compound, 3A, the preparation of 1-substituted benzimidazoles (4A) was attempted. However, the inhibitory effect of 4A against gastric acid secretion was less potent than that of 3A. Then 3A was solvated by EtOH or H2O to afford 5A or 6A, respectively. On the other hand, an another diastereoisomer, (R*s,9R*)-3B, was not solvated by EtOH or H2O under the same conditions. The thus obtained solvates (5A, 6A) are much more stable than that of 3A. The antiulcer activities of 5A and 6A were found to be similar to that of the parent compound (3A). Consequently, 6A was selected as an antiulcer agent for the development.

  12. cyclo-Tetra-μ-malato-κ16 O,O′,O′′:O′′′-tetra­kis[bis­(1H-benzimidazole-κN 3)cobalt(II)] eicosa­hydrate (United States)

    Li, Jun-Hua; Nie, Jing-Jing; Su, Jian-Rong; Xu, Duan-Jun


    The title compound, [Co4(C4H4O5)4(C7H6N2)8]·20H2O, consists of tetra­nuclear CoII complexes and disordered uncoordinated water mol­ecules. The tetra­meric complex mol­ecule has symmetry. While two benzimidazole mol­ecules and a tridentate malate dianion coordinate a CoII ion, the carboxylate O atom from an adjacent malate dianion bridges the CoII ions to complete a distorted octa­hedral coordination geometry. The tridentate malate dianion chelates the CoII ion, and the chelate six- and five-membered rings show half-chair and envelope configurations, respectively. A face-to-face separation of 3.494 (9) Å between parallel benzimidazole ligands indicates the existence of π–π stacking between adjacent complexes. The crystal structure also involves N—H⋯O and O—H⋯O hydrogen bonds. PMID:21201998

  13. 三元TBZ/HPB-铜(Ⅱ)-L-蛋氨酸配合物的合成、表征、抑菌活性及与DNA的作用%Syntheses, Characterization, Antibacterial Activities of Ternary Copper(Ⅱ)Complexes with 2-(4′-Thiazolyl)benzimidazole/2-(2-pyridyl)benzimidazole and L-Methionine and Their Interaction with DNA

    Institute of Scientific and Technical Information of China (English)

    卢艳梅; 区志镔; 刘海峰; 乐学义


    本文合成了2个新的三元铜(Ⅱ)配合物:[Cu(TBZ)(L-Met)(H2O)]ClO4·H2O(1)和[Cu(HPB)(L-Met)]ClO4(2)[TBZ=2-(4′-噻唑基)苯并咪唑,HPB=2-(2-吡啶)苯并咪唑,L-Met=L-蛋氨酸].通过元素分析、摩尔电导率、IR、UV-Vis及电喷雾质谱对这些配合物进行了表征.用二倍稀释法研究了配合物的抗菌活性,发现配合物对金黄色葡萄球菌(Staphylococcus aureus,G+),枯草杆菌(Bacillus subtilis,G+),沙门氏杆菌(Salmonella,G-)和大肠杆菌(Escherichia coil,G-)具有良好的抑制作用.采用电子吸收光谱、荧光光谱、粘度测定及琼脂凝胶电泳方法研究了配合物与DNA的相互作用,结果表明,配合物以插入方式与DNA作用,在维生素C存在下通过羟自由基·OH,单线态氧1O2或者1O2类似物如Cu-O2,切割pBR322 DNA双螺旋结构.%Two new ternary copper(Ⅱ) complexes: [Cu(TBZ)(L-Met)(H2O)]ClO4.H2O (1) and [Cu(HPB)(L-Met)]ClO4 (2) [TBZ=2-(4'-thiazolyl)benzimidazole, HPB=2-(2-pyridyl)benzimidazole, L-Met=L-methionine], were synthesized and characterized by elemental analysis, molar conductivity, IR, UV-Vis spectroscopy and ES-MS. The complexes were assayed against gram-positive (Staphylococcus aureus, Bacillus subtilis) and gram-negative (Salmonella,Escherichia coil) bacteria by doubling dilutions method, and the interaction of the complexes to DNA was investigated by electronic absorption spectroscopy, fluorescence spectroscopy, viscosity measurements and agarose gel electrophoresis. The results indicated that the complexes could bind to DNA by intercalative mode, and cleave pBR322 DNA in the presence of vitamin C in the involvement of the hydroxyl radical,and may be a singlet oxygen or a singlet oxygen-like entity such as copper-peroxide Cu-O2, with the order of the binding ability and cleavage activity of the complexes to DNA: complex 2>1.

  14. (Dimethylformamide-κO(2-hydroxybenzoato-κ2O1,O1′[tris(1-methyl-1H-benzimidazol-2-ylmethyl-κN3amine-κN]manganese(II perchlorate dimethylformamide monosolvate

    Directory of Open Access Journals (Sweden)

    Baoliang Qi


    Full Text Available In the title complex, [Mn(C7H5O3(C27H27N7(C3H7NO]ClO4·C3H7NO, the MnII ion is coordinated in a slightly distorted monocapped trigonal-prismatic geometry. The tris(1-methyl-1H-benzimidazol-2-ylmethylamine (Mentb ligand coordinates in a tetradentate mode and the coordination is completed by a bis-chelating salicylate ligand and a dimethylformamide ligand. The hydroxy group and the ortho H atoms of the salicylate ligand were refined as disordered over two sites with occupancies of 0.581 (8 and 0.419 (8. Both disorder components of the hydroxy group form intramolecular O—H...O hydrogen bonds.

  15. Hybrid proton-conducting membranes for polymer electrolyte fuel cells. Phosphomolybdic acid doped poly(2,5-benzimidazole) - (ABPBI-H{sub 3}PMo{sub 12}O{sub 40})

    Energy Technology Data Exchange (ETDEWEB)

    Gomez-Romero, Pedro [Institut de Ciencia de Materials de Barcelona (CSIC), Campus UAB, E-08193 Bellaterra (Barcelona) (Spain); Asensio, Juan Antonio [Institut de Ciencia de Materials de Barcelona (CSIC), Campus UAB, E-08193 Bellaterra (Barcelona) (Spain); Institut Quimic de Sarria, Universitat Ramon Llull, Via Augusta 390, E-08017 Barcelona (Spain); Borros, Salvador [Institut Quimic de Sarria, Universitat Ramon Llull, Via Augusta 390, E-08017 Barcelona (Spain)


    The synthesis and characterization of a novel hybrid organic-inorganic material formed by phosphomolybdic acid H{sub 3}PMo{sub 12}O{sub 40} (PMo{sub 12}) and poly(2,5-benzimidazole) (ABPBI) is reported. This material, composed of two proton-conducting components, can be cast in the form of membranes from methanesulfonic acid (MSA) solutions. Upon impregnation with phosphoric acid, the hybrid membranes present higher conductivity than the best ABPBI polymer membranes impregnated in the same conditions. These electrolyte membranes are proposed. (author). An equivalproton conductivity of 3 x 10{sup -2} S cm{sup -1} at 185 C without humidification. These properties make them very good candidates as membranes for polymer electrolyte membrane fuel cells (PEMFC) at temperatures of 100-200 C. (author)

  16. Synthesis and Biological Activity of 2-(Thiazolidin-4-One Phenyl]-1h-Phenylbenzimidazoles and 2-[4-(Azetidin-2-One-3-Chloro-4- Phenyl] -1h-Phenyl Benzimidazoles

    Directory of Open Access Journals (Sweden)

    P. Shanmugapandiyan


    Full Text Available A new series of 2-[4-(azetidin-2-one-3-Chloro-4-phenyl]-1H-Phenylbenzimidazoles and 2-(thiazolidin-4-one-Phenyl]-1H-Phenylbenzimidazoles were synthesized by the reaction of schiff base [2-(4-aminophenyl-Benzimidazole and substituted Benzaldehyde] with chloroacetyl chloride and mercaptoacetic acid respectively. The chemical structures of the synthesized compounds were confirmed by IR, 1H-NMR, mass spectral and C, H, N analysis. The synthesized compounds were screened for antibacterial (Bacillus cereus, Escherichia coli, Micrococcus luteus, Klebssiela pneumoniae, Staphylococcus aureus and Salmonella epidermidis, antifungal (Aspergillus niger and Candida albicans, analgesic activity by writhing reflex method and anti-inflammatory activity by carrageenan induced paw edema method. The synthesized compound showed significant activity of antibacterial, antifungal, analgesic and anti-inflammatory activity comparable to that of standard.

  17. Bis[μ-2,2′-dimethyl-1,1′-(oxydiethylenebis(1H-benzimidazole-κ2N3:N3′]bis[bis(4-methoxybenzoato-κ2O,O′cadmium(II

    Directory of Open Access Journals (Sweden)

    Dian-Ying Zhao


    Full Text Available The title complex, [Cd2(C8H7O34(C20H22N4O2], forms a dimer of the paddle-wheel type, located on a crystallographic inversion centre. The CdII ion is hexacoordinated by four carboxylate O atoms [Cd...O = 2.280 (2–2.404 (2 Å] from two chelating 4-methoxybenzoate anions, and two N atoms [Cd...N = 2.313 (2 and 2.332 (2 Å] from one chelating 2,2′-dimethyl-3,3′-(oxydiethylenebis(1H-benzimidazole ligand. In the crystal, molecules are linked by a weak intermolecular C—H...O hydrogen bond and an intermolecular C—H...π interaction.

  18. Synthesis, characterization and antimicrobial activity of Fe(II), Zn(II), Cd(II) and Hg(II) complexes with 2,6-bis(benzimidazol-2-yl) pyridine ligand. (United States)

    Aghatabay, Naz M; Neshat, A; Karabiyik, T; Somer, M; Haciu, D; Dülger, B


    2,6-Bis(benzimidazol-2-yl)pyridine (L) ligand and complexes [M(L)Cl(2)] and [Fe(L)(2)](ClO(4))(2) (M=Zn, Cd, Hg) have been synthesized. The geometries of the [M(L)Cl(2)] complexes were derived from theoretical calculation in DGauss/DFT level (DZVP basis set) on CACHE. The central M(II) ion is penta-coordinated and surrounded by N(3)Cl(2) environment, adopting a distorted trigonal bipyramidal geometry. The ligand is tridentate, via three nitrogen atoms to metal centre and two chloride ions lie on each side of the distorted benzimidazole ring. In the [Fe(L)(2)](ClO(4))(2) complex, the central Fe(II) ion is surrounded by two (3N) units, adopting a octahedral geometry. The elemental analysis, molecular conductivity, FT-Raman, FT-IR (mid-, far-IR), (1)H, and (13)C NMR were reported. The antimicrobial activities of the free ligand, its hydrochloride salt, and the complexes were evaluated using the disk diffusion method in dimethyl sulfoxide (DMSO) as well as the minimal inhibitory concentration (MIC) dilution method, against 10 bacteria and the results compared with that for gentamycin. Antifungal activities were reported for Candida albicans, Kluyveromyces fragilis, Rhodotorula rubra, Debaryomyces hansenii, Hanseniaspora guilliermondii, and the results were referenced against nystatin, ketaconazole, and clotrimazole antifungal agents. In most cases, the compounds tested showed broad-spectrum (Gram positive and Gram negative bacteria) activities that were either more effective than or as potent as the references. The binding of two most biologically effective compounds of zinc and mercury to calf thymus DNA has also been investigated by absorption spectra.

  19. Structural, spectroscopic, and electrochemical properties of tri- and tetradentate N3 and N3S copper complexes with mixed benzimidazole/thioether donors. (United States)

    Castillo, Ivan; Ugalde-Saldívar, Víctor M; Rodríguez Solano, Laura A; Sánchez Eguía, Brenda N; Zeglio, Erica; Nordlander, Ebbe


    Cupric and cuprous complexes of bis(2-methylbenzimidazolyl)(2-methylthiophene)amine (L(1)), bis(2-methylbenzimidazolyl)benzylamine (L(2)), bis(2-methylbenzimidazolyl)(2,4-dimethylphenylthioethyl)amine (L(3)), bis(1-methyl-2-methylbenzimidazolyl)benzylamine (Me(2)L(2)), and bis(1-methyl-2-methylbenzimidazolyl)(2,4-dimethylphenylthioethyl)amine (Me(2)L(3)) have been spectroscopically, structurally, and electrochemically characterised. The thioether-containing ligands L(3) and Me(2)L(3) give rise to complexes with Cu-S bonds in solution and in the solid state, as evidenced by UV-vis spectroscopy and X-ray crystallography. The Cu(2+) complexes [L(1)CuCl(2)] (1), [L(2)CuCl(2)] (2) and [Me(2)L(3)CuCl]ClO(4) (3(Me,ClO4)) are monomeric in solution according to ESI mass spectrometry data, as well as in the solid state. Their Cu(+) analogues [L(1)Cu]ClO(4), [L(2)Cu]ClO(4), [L(3)Cu]ClO(4) (4-6), [BOC(2)L(1)Cu(NCCH(3))]ClO(4) (4(BOC)), [Me(2)L(2)Cu(NCCH(3))(2)]PF(6) (5(Me)) and [Me(2)L(3)Cu](2)(ClO(4))(2) (6(Me)) are also monomeric in acetonitrile solution, as confirmed crystallographically for 4(BOC) and 5(Me). In contrast, 6(Me) is dimeric in the solid state, with the thioether group of one of the ligands bound to a symmetry-related Cu(+) ion. Cyclic voltammetry studies revealed that the bis(2-methylbenzimidazolyl)amine-Cu(2+)/Cu(+) systems possess half-wave potentials in the range -0.16 to -0.08 V (referenced to the ferrocenium-ferrocene couple); these values are nearly 0.23 V less negative than those reported for related bis(picolyl)amine-derived ligands. Based on these observations, the N(3) or N(3)S donor set of the benzimidazole-derived ligands is analogous to previously reported chelating systems, but the electronic environment they provide is unique, and may have relevance to histidine and methionine-containing metalloenzymes. This is also reflected in the reactivity of [Me(2)L(2)Cu(NCCH(3))(2)](+) (5(Me)) and [Me(2)L(3)Cu](+) (6(Me)) towards dioxygen, which results

  20. Novel pyrazolo[3,4-d]pyrimidine with 4-(1H-benzimidazol-2-yl)-phenylamine as broad spectrum anticancer agents: Synthesis, cell based assay, topoisomerase inhibition, DNA intercalation and bovine serum albumin studies. (United States)

    Singla, Prinka; Luxami, Vijay; Singh, Raja; Tandon, Vibha; Paul, Kamaldeep


    A series of new pyrazolo[3,4-d]pyrimidine possessing 4-(1H-benzimidazol-2-yl)-phenylamine moiety at C4 position and primary as well as secondary amines at C6 position has been designed and synthesized. Their antitumor activities were evaluated against a panel of 60 human cancer cell lines at National Cancer Institute (NCI). Six compounds displayed potent and broad spectrum anticancer activities at 10 μM. Compounds 8, 12, 14 and 17 proved to be the most active and efficacious candidate in this series, with mean GI50 values of 1.30 μM, 1.43 μM, 2.38 μM and 2.18 μM, respectively against several cancer cell lines. Further biological evaluation of these compounds suggested that these compounds induce apoptosis and inhibit human topoisomerase (Topo) IIα as a possible intracellular target. UV-visible and fluorescence studies of these compounds revealed strong interaction with ct-DNA and bovine serum albumin (BSA).

  1. Structural requirements of some 2-(1-propylpiperidin-4-yl)-1H-benzimidazole-4-carboxamide derivatives as poly (ADP-ribose) polymerase (PARP) for the treatment of cancer: QSAR approach. (United States)

    Sharma, Mukesh C


    The present study is aimed to elucidate the structural features of substituted 2-(1-propylpiperidin-4-yl)-1H-benzimidazole-4-carboxamide required for poly (ADP-ribose) polymerase inhibition and to obtain predictive 2D QSAR models to guide the rational synthesis of novel poly (ADP-ribose) polymerase inhibitors. The statistical analysis has shown that excellent results are obtained by using partial least regression based on simulated annealing method. The best model was selected based on the highest correlation coefficient r(2) = 0.8590 and cross validated squared correlation coefficient q(2) = 0.7875 with external predictive ability of pred_r(2) = 0.7407 was developed by stepwise PLS method with the descriptors like T_N_F_1, SdsCHcount, and Rotatable Bond Count. The generated models provide insight into the influence of various interactive fields on the activity and, thus, can help in designing and forecasting the inhibition activity of novel (ADP-ribose) polymerase molecules.

  2. In vitro characterization of a novel C,N-cyclometalated benzimidazole Ru(II) arene complex: stability, intracellular distribution and binding, effects on organic osmolyte homeostasis and induction of apoptosis. (United States)

    Støving Dam, Celina; Alejo Perez Henarejos, Sergio; Tsolakou, Theodosia; Alexander Segato, Christian; Gammelgaard, Bente; Yellol, Gorakh S; Ruiz, José; Lambert, Ian Henry; Stürup, Stefan


    In the present work a novel C,N-cyclometalated benzimidazole Ru(ii) arene complex (GY34) was characterized by applying an alternative, diverse approach considering both chemical and biological aspects. RP-HPLC-ICP-MS and RP-HPLC-ESI-MS analysis proved that GY34 in both RPMI-1640 cell medium and ammonium acetate buffer was transformed into several subspecies and the importance of evaluating and controlling analyte stability throughout experiments was demonstrated. Applying a novel cell fractionation protocol GY34 was found to target cell nuclei and mitochondria in Ehrlich Lettré Ascites (ELA) cells, with the intracellular distribution depending on GY34 concentration in the cell medium during incubation. In ELA cells 96 ± 0.2% of cytosolic GY34 was bound to high-molecular species. Furthermore, using the tracer technique GY34 was found to reduce uptake and increase release of the organic osmolyte taurine in ELA cells, with innate resistance to Cisplatin and in A2780 human ovarian cancer cells, with acquired resistance to Cisplatin. Importantly, FACS analysis revealed that GY34 induced apoptosis in ELA cells. The present data suggest the potential of GY34 in overcoming Cisplatin resistance. The methodology applied can be used as a general protocol and an additional tool in the initial evaluation of novel metal-based drugs.

  3. Structural Requirements of Some 2-(1-Propylpiperidin-4-yl)-1H-benzimidazole-4-carboxamide Derivatives as Poly (ADP-Ribose) Polymerase (PARP) for the Treatment of Cancer: QSAR Approach. (United States)

    Sharma, Mukesh C


    The present study is aimed to elucidate the structural features of substituted 2-(1-propylpiperidin-4-yl)-1H-benzimidazole-4-carboxamide required for poly (ADP-ribose) polymerase inhibition and to obtain predictive 2D QSAR models to guide the rational synthesis of novel poly (ADP-ribose) polymerase inhibitors. The statistical analysis has shown that excellent results are obtained by using partial least regression based on simulated annealing method. The best model was selected based on the highest correlation coefficient r (2) = 0.8590, and cross-validated squared correlation coefficient q (2) = 0.7875 with external predictive ability of [Formula: see text] was developed by stepwise PLS method with the descriptors like T_N_F_1, SdsCHcount, and Rotatable Bond Count. The generated models provide insight into the influence of various interactive fields on the activity and, thus, can help in designing and forecasting the inhibition activity of novel (ADP-ribose) polymerase molecules.

  4. Crystal structure of (2,2′-bipyrid­yl)[2,6-bis­(1-butyl-1H-benzimidazol-2-yl)pyridine]­chlorido­iridium(III) tri­fluoro­methane­sulfonate (United States)

    Smith, Victoria I.; Zeller, Matthias


    The title complex compound, [Ir(C27H29N5)Cl(C10H8N2)](CF3SO3)2, was synthesized for a study of iridium(III)/periodate redox systems in water. The coordination geometry of the complex can be best described as distorted octa­hedral, with an r.m.s. deviation of 8.8 (8)% from ideal octa­hedral rectangular geometry. In the crystal, C—H⋯O and C—H⋯F inter­actions between the complex cation and the tri­fluoro­methane­sulfonate anions are observed, as well as a C—H⋯Cl inter­molecular inter­action between neighboring complex cations. In addition, the benzimidazole ring systems display parallel-displaced π–π stacking with centroid–centroid distances of 3.585 (3)–3.907 (3) Å. One of the two tri­fluoro­methane­sulfonate anions is disordered over two orientations with an occupancy ratio of 0.582 (6):0.418 (6). The title complex was characterized using FT–IR, cyclic voltammetry/rotating disc electrode polarography, fluorescence spectrometry, high resolution mass spectrometry, CHN elemental analysis and 1H NMR spectroscopy. PMID:28217326

  5. (2-Benzoyl-1-phenylethenolato-κ2O,O′bis[2-(1-phenyl-1H-benzimidazol-2-ylphenyl-κC1]iridium(III dichloromethane disolvate

    Directory of Open Access Journals (Sweden)

    Stanislav I. Bezzubov


    Full Text Available We present here synthesis and crystal structure of a neutral IrIII complex, [Ir(C19H13N22(C15H11O2]·2CH2Cl2 or [Ir(C^N2O^O]·2CH2Cl2, where C^N is 1,2-diphenyl-1H-benzimidazole and O^O is 2-benzoyl-1-phenylethenolate. The coordination sphere of the IrIII atom, located on a twofold rotation axis, is that of a slighlty distorted C2N2O2 octahedron, with the N atoms in a trans configuration. In the crystal, complex molecules assemble through weak C—H...π interactions in the range 2.699 (3–2.892 (3 Å. The solvent CH2Cl2 molecules reside in channels aligned along the a axis and are connected to the complex molecules by C—H...O interactions.

  6. Multiresidue screening method for detection of benzimidazoles and their metabolites in liver and muscle by high-performance liquid chromatography: method development and validation according to Commission Decision 2002/657/EC

    Directory of Open Access Journals (Sweden)

    Marilena Gili


    Full Text Available The use of veterinary drugs may cause the presence of residues in food of animal origin if appropriate withdrawal periods are not respected. A high-performance liquid chromatography (HPLC method has been developed for the simultaneous detection of 11 benzimidazole residues, including metabolites – albendazole, albendazole sulphoxide, albendazole sulphone, fenbendazole, fenbendazole sulphoxide (oxfendazole, fenbendazole sulphone, flubendazole, mebendazole, oxibendazole, thiabendazole, 5-hydroxythiabendazole – in bovine, ovine, equine, swine, rabbit and poultry liver and in bovine, swine and fish muscle. After extraction with a dicloromethane/acetonitrile solution (35/65 v/v containing 5% ammonium hydroxide, the solvent was evaporated to dryness, the residue was dissolved in HCl 0.1 M, defatted with hexane, purified on a strong cation exchange solid-phase extraction cartridge and analysed in HPLC with diode array and fluorescence detectors. The method was validated as screening qualitative method evaluating, according to Commission Decision 2002/657/EC criteria, specificity, CCb and b error at cut off level of 25 mg/kg and ruggedness.

  7. De novo design, synthesis and spectroscopic characterization of chiral benzimidazole-derived amino acid Zn(II) complexes: Development of tryptophan-derived specific hydrolytic DNA artificial nuclease agent (United States)

    Parveen, Shazia; Arjmand, Farukh


    Novel ternary dizinc(II) complexes 1- 3, derived from 1,2-bis(1H-benzimidazol-2-yl)ethane-1,2-diol and L-form of amino acids (viz., tryptophan, leucine and valine) were synthesized and characterized by spectroscopic (IR, 1H NMR, UV-vis, ESI-MS) and other analytical methods. To evaluate the biological preference of chiral drugs for inherently chiral target DNA, interaction of 1- 3 with calf thymus DNA in Tris-HCl buffer was studied by various biophysical techniques which reveal that all these complexes bind to CT DNA non-covalently via electrostatic interaction. The higher Kb value of L-tryptophan complex 1 suggested greater DNA binding propensity. Further, to evaluate the mode of action at the molecular level, interaction studies of complexes 1 and 2 with nucleotides (5'-GMP and 5'-TMP) were carried out by UV-vis titrations, 1H and 31P NMR which implicates the preferential selectivity of these complexes to N3 of thymine rather than N7 of guanine. Furthermore, complex 1 exhibits efficient DNA cleavage with supercoiled pBR322. The complex 1 cleaves DNA efficiently involving hydrolytic cleavage pathway. Such chiral synthetic hydrolytic nucleases with asymmetric centers are gaining considerable attention owing to their importance in biotechnology and drug design, in particular to cleave DNA with sequence selectivity different from that of the natural enzymes.

  8. Synthesis and Structure of a 3D Manganese Coordination Polymer with 1,3-Bis(benzimidazol-1-ylmethyl)-2,4,6-trimethylbenzene and 1,5-Naphthalenedisulfonate

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hui; DU Shao-Wu; LI Zhi-Hua


    The organic-inorganic hybrid polymer [Mn(mbbimb)2(1,5-nds)]n 1 has been synthesized using 1,5-naphthalenedisulfonate (1,5-nds) and 1,3-bis(benzimidazol-1-ylmethyl)- 2,4,structure analysis indicates that 1 crystallizes in monoclinic, space group C2/c with a=21.3546(17), b=11.8841(7), c=22.1588(16) (A), β=108.058(3)°, C60H54MnN8O6S2, Mr=1102.17, Z=4, V=5346.5(7)(A)3, Dc=1.369 g/cm3, μ=0.386 mm-1, F(000)=2300, S=1.091, R=0.0634 and wR=0.1559 for 4641 observed reflections (I > 2σ(I)). The Mn center is six-coordinated to furnish a distorted octahedral geometry, and the overall framework is a 6-connected 3D net.

  9. Synthesis and Anti-inflammatory Activity of Novel Benzimidazole (Benzothiazole) Phenylursolate%新型熊果酸苯并咪(噻)唑连苯酯合成及抗炎活性测定

    Institute of Scientific and Technical Information of China (English)

    李财虎; 杨聪玲; 张宽; 石万棋; 李剑忠; 李颖; 尹述凡


    以熊果酸、取代苯甲醛和邻苯二胺或邻氨基苯硫酚为原料,合成了一系列熊果酸苯并咪(噻)唑连苯酯衍生物4a~4h,8个新化合物均未见文献报道,其结构经1H NMR,IR和HRMS加以确认,并对4a~4h进行药理活性筛选,结果表明,化合物4d (150 mg·kg-1),4g (150 mg·kg-1)等具有良好抗炎活性.%A novel series of the benzimidazole or benzothiazole phenyl ester derivatives of ursolic acid 4a~4h were prepared via ursolic acid, substituted benzaldehyde, and o-phenylendiamine or 2-aminothiophenol. The compounds were structurally confirmed by 'H NMR, 1R and HRMS techniques. The preliminary bioassay test demonstrated that compounds 4d and 4g had potent anti-inflammatory activity.

  10. Alternative solvent-based methyl benzoate vortex-assisted dispersive liquid-liquid microextraction for the high-performance liquid chromatographic determination of benzimidazole fungicides in environmental water samples. (United States)

    Santaladchaiyakit, Yanawath; Srijaranai, Supalax


    Vortex-assisted dispersive liquid-liquid microextraction using methyl benzoate as an alternative extraction solvent for extracting and preconcentrating three benzimidazole fungicides (i.e., carbendazim, thiabendazole, and fluberidazole) in environmental water samples before high-performance liquid chromatographic analysis has been developed. The selected microextraction conditions were 250 μL of methyl benzoate containing 300 μL of ethanol, 1.0% w/v sodium acetate, and vortex agitation speed of 2100 rpm for 30 s. Under optimum conditions, preconcentration factors were 14.5-39.0 for the target fungicides. Limits of detection were obtained in the range of 0.01-0.05 μg/L. The proposed method was then applied to surface water samples and the recovery evaluations at three spiked concentration levels of 5, 30, and 50 μg/L were obtained in the range of 77.4-110.9% with the relative standard deviation water samples.

  11. Mononuclear and Binuclear Ruthenium(II) Complexes Containing 2,2'-Bipyridine or 1,10-Phenanthroline and Pyrazole-3,5-Bis(benzimidazole). Synthesis, Structure, Isomerism, Spectroscopy, and Proton-Coupled Redox Activity. (United States)

    Baitalik, Sujoy; Flörke, Ulrich; Nag, Kamalaksha


    A number of mixed-ligand mononuclear and binuclear ruthenium(II) complexes of composition [(bpy)(2)Ru(H(3)pzbzim)](ClO(4))(2).2H(2)O (1), [(phen)(2)Ru(H(3)pzbzim)](ClO(4))(2).3H(2)O (2), [(bpy)(2)Ru(H(2)pzbzim)Ru(bpy)(2)](ClO(4))(3).5H(2)O (3), [(phen)(2)Ru(H(2)pzbzim)Ru(phen)(2)](ClO(4))(3).4H(2)O (4), [(bpy)(2)Ru(H(2)pzbzim)Ru(phen)(2)](ClO(4))(3).4H(2)O (5), [(bpy)(2)Ru(pzbzim)Ru(bpy)(2)](ClO(4)).3H(2)O (6), and [(phen)(2)Ru(pzbzim)Ru(phen)(2)](ClO(4)).2H(2)O (7), where H(3)pzbzim = pyrazole-3,5-bis(benzimidazole), bpy = 2,2'-bipyridine, and phen = 1,10-phenanthroline, have been prepared and characterized. Complexes 3-5 isolated as mixtures of diastereoisomers have been separated by fractional recrystallization. In the cases of 3 and 4, the meso (LambdaDelta) and racemate (rac) (LambdaLambda, DeltaDelta) forms, and for 5, two enantiomeric pairs [(LambdaDelta, DeltaLambda) and (LambdaLambda, DeltaDelta)] have been obtained. These, as well as the meso and rac diastereoisomers of 6, have been characterized by (1)H and (13)C NMR spectroscopy. The crystal structure of the meso (LambdaDelta) form of 3 (C(57)H(53)N(14)Cl(3)O(17)Ru(2)) has been determined, which crystallizes in the monoclinic space group P2(1)/c with a = 11.672(2) Å, b = 41.696(9) Å, c = 12.871(2) Å, beta = 90.03(2)(o), and Z = 4. The acid-base and redox chemistry of the binuclear complexes has been studied over the pH range 1-12 in acetonitrile-water (3:2) medium. The equilibrium constants of the species involving protonation and deprotonation of the benzimidazole NH protons and the metal oxidation states covering +2 and +3 have been evaluated by spectrophotometric and cyclic voltammetric measurements. During spectrophotometric titrations of the complexes with cerium(IV), the metal-to-ligand charge transfer transitions are replaced by the newly generated ligand-to-metal charge transfer transition. The luminescence spectra of the complexes in solution (at 298 K) and in frozen glass (at 77 K) and

  12. Synthesis, structural characterization, solution behavior, and in vitro antiproliferative properties of a series of gold complexes with 2-(2'-pyridyl)benzimidazole as ligand: comparisons of gold(III) versus gold(I) and mononuclear versus binuclear derivatives. (United States)

    Serratrice, Maria; Cinellu, Maria A; Maiore, Laura; Pilo, Maria; Zucca, Antonio; Gabbiani, Chiara; Guerri, Annalisa; Landini, Ida; Nobili, Stefania; Mini, Enrico; Messori, Luigi


    A variety of gold(III) and gold(I) derivatives of 2-(2'-pyridyl)benzimidazole (pbiH) were synthesized and fully characterized and their antiproliferative properties evaluated in a representative ovarian cancer cell line. The complexes include the mononuclear species [(pbi)AuX(2)] (X = Cl, 1; OAc, 2), [(pbiH)AuCl] (3), [(pbiH)Au(PPh(3))][PF(6)] (4-PF(6)), and [(pbi)Au(L)] (L = PPh(3), 5; TPA, 6), and the binuclear gold(I)/gold(I) and gold(I)/gold(III) derivatives [(PPh(3))(2)Au(2)(μ(2)-pbi)][PF(6)] (10-PF(6)), [ClAu(μ(3)-pbi)AuCl(2)] (7),and [(PPh(3))Au(μ(3)-pbi)AuX(2)][PF(6)] (X = Cl, 8-PF(6); OAc, 9-PF(6)). The molecular structures of 6, 7, and 10-PF(6) were determined by X-ray diffraction analysis. The chemical behavior of these compounds in solution was analyzed both by cyclic voltammetry in DMF and absorption UV-vis spectroscopy in an aqueous buffer. Overall, the stability of these gold compounds was found to be acceptable for the cellular studies. For all complexes, relevant antiproliferative activities in vitro were documented against A2780 human ovarian carcinoma cells, either resistant or sensitive to cisplatin, with IC(50) values falling in the low micromolar or even in the nanomolar range. The investigated gold compounds were found to overcome resistance to cisplatin to a large degree. Results are interpreted and discussed in the frame of current knowledge on cytotoxic and antitumor gold compounds.

  13. Microwave-Assisted Syntheses of Benzimidazole-Containing Selenadiazole Derivatives That Induce Cell-Cycle Arrest and Apoptosis in Human Breast Cancer Cells by Activation of the ROS/AKT Pathway. (United States)

    Liang, Yuanwei; Zhou, Yangliang; Deng, Shulin; Chen, Tianfeng


    The use of selenium-containing heterocyclic compounds as potent cancer chemopreventive and chemotherapeutic agents has been well documented by a large number of clinical studies. In this study we developed a new approach to synthesize four benzimidazole-containing selenadiazole derivatives (BSeDs). The method uses a combination of peptide coupling reagents and microwave irradiation. This strategy features milder reaction conditions, higher yields, and shorter reaction times. The synthetic BSeDs were identified as potent antiproliferative agents against the human MCF-7 and MDA-MB-231 breast cancer cell lines. Compounds 1 b (5-(6-methyl-1H-benzo[d]imidazol-2-yl)benzo[c][1,2,5]selenadiazole), 1 c (5-(6-chloro-1H-benzo[d]imidazol-2-yl)benzo[c][1,2,5]selenadiazole), and 1 d (5-(6-bromo-1H-benzo[d]imidazol-2-yl)benzo[c][1,2,5]selenadiazole) were found to show greater cytotoxicity against the triple-negative breast cancer cell line MDA-MB-231 than MCF-7, and to exhibit dose-dependent inhibition of cell migration, in which a significant decrease in the zone of cell monolayer wound closure was observed relative to untreated controls. Our results demonstrate that BSeDs can cause cell-cycle arrest and apoptosis in MDA-MB-231 cells by inducing DNA damage, inhibiting protein kinase B (AKT), and activating mitogen-activated protein kinase (MAPK) family members through the overproduction of reactive oxygen species (ROS). Taken together, the results of this study provide a facile microwave-assisted strategy for the synthesis of selenium-containing organic compounds that exhibit a high level of anticancer efficacy.

  14. Impairment of the ubiquitin-proteasome pathway by methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl)carbamate leads to a potent cytotoxic effect in tumor cells: a novel antiproliferative agent with a potential therapeutic implication. (United States)

    Dogra, Nilambra; Mukhopadhyay, Tapas


    In recent years, there has been a great deal of interest in proteasome inhibitors as a novel class of anticancer drugs. We report that fenbendazole (FZ) (methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl)carbamate) exhibits a potent growth-inhibitory activity against cancer cell lines but not normal cells. We show here, using fluorogenic substrates, that FZ treatment leads to the inhibition of proteasomal activity in the cells. Succinyl-Leu-Leu-Val-Tyr-methylcoumarinamide (MCA), benzyloxycarbonyl-Leu-Leu-Glu-7-amido-4-MCA, and t-butoxycarbonyl-Gln-Ala-Arg-7-amido-4-MCA fluorescent derivatives were used to assess chymotrypsin-like, post-glutamyl peptidyl-hydrolyzing, and trypsin-like protease activities, respectively. Non-small cell lung cancer cells transiently transfected with an expression plasmid encoding pd1EGFP and treated with FZ showed an accumulation of the green fluorescent protein in the cells due to an increase in its half-life. A number of apoptosis regulatory proteins that are normally degraded by the ubiquitin-proteasome pathway like cyclins, p53, and IκBα were found to be accumulated in FZ-treated cells. In addition, FZ induced distinct ER stress-associated genes like GRP78, GADD153, ATF3, IRE1α, and NOXA in these cells. Thus, treatment of human NSCLC cells with fenbendazole induced endoplasmic reticulum stress, reactive oxygen species production, decreased mitochondrial membrane potential, and cytochrome c release that eventually led to cancer cell death. This is the first report to demonstrate the inhibition of proteasome function and induction of endoplasmic reticulum stress/reactive oxygen species-dependent apoptosis in human lung cancer cell lines by fenbendazole, which may represent a new class of anticancer agents showing selective toxicity against cancer cells.

  15. 基于苯并咪唑的超分子金属有机凝胶及其刺激响应性能研究%Benzimidazole-based supramolecular metallogel and its stimuli responsivenesses

    Institute of Scientific and Technical Information of China (English)

    姚虹; 吴红平; 常静; 魏太保; 张有明


    合成了一种基于羧基功能化的苯并咪唑类有机凝胶因子(C11)。该凝胶因子在水‐乙醇体系中不仅能自组装成超分子有机凝胶(C11‐OG),而且与银离子络合后可以自组装成具有多重刺激响应性能的金属凝胶(Ag‐MG)。有机凝胶C11‐OG和金属凝胶Ag‐MG都具有凝聚态荧光增强(AIEE)的性能。金属凝胶Ag‐MG可对温度、EDTA和Na2S的刺激进行可逆的溶液‐凝胶变化响应及荧光响应。此外,通过扫描电镜(SEM )、X射线衍射(XRD)和红外光谱(FT‐IR)研究了其刺激响应机理。%In this paper ,a simple carboxylic‐functionalized benzimidazole gelator(C11) is prepared . This gelator can self‐assembled to supramolecular organogel and metallogel (C11‐OG and Ag‐MG) in EtOH‐H2 O with multi‐stimuli responsive properties . Besides , the organogel C11‐OG and metallogel Ag‐MG have dramatic aggregation‐induced fluorescence emission enhancement (AIEE ) . The Ag‐MG reveals outstanding reversible sol‐gel transitions and fluorescent changes induced by changing of temperature , EDTA and Na2S .In addition ,the stimuli‐responsive mechanism is tested by SEM ,XRD and FT‐IR .

  16. Cadmium(Ⅱ) Nitrite Complex Based on the Bis(2-benzimidazole) and Aromatic Carboxylate Ligands%Cadmium(Ⅱ) Nitrite Complex Based on the Bis(2-benzimidazole) and Aromatic Carboxylate Ligands

    Institute of Scientific and Technical Information of China (English)

    JIANG Luan; FENG Guo-Dong; CHEN Qiang; YANG De-Suo; LI Zong-Xiao; LUO Xiao-Lin


    A new cadmium(Ⅱ) nitrite complex Cd2(H2C3PIm)2(BDC)(NO2)2(1,H2C3PIm = 2,2'-(1,3-propanediyl)bis(1H-benzimidazole),H2BDC = 1,4-benzenedicarboxylic acid) has been synthesized by solvothermal reaction in formamide,and its structure(C42H36Cd2N10O8,Mr = 1033.61) was determined by single-crystal X-ray diffraction analysis.The crystal belongs to the monoclinic system,space group P21/n with a = 0.9859(5),b = 0.8936(5),c = 2.3188(5) nm,β = 97.576(5)°,V = 2.025(16) nm3,Z = 2,Dc = 1.695 g/cm3,μ(MoKα) = 1.118 mm-1,F(000) = 1036,S = 1.017,the final R = 0.0304 and wR = 0.0752 for 3761 reflections with I 〉 2σ(I).The centrosymmetric complex 1 contains a dimer in which two distorted octahedral Cd(II) centers are bridged by BDC ligand and chelated by H2C3PIm.The units of the complex are linked via weak N-H···O hydrogen bonds between the nitrito and the BDC ligands,leading to the formation of a 1D zigzag chain along the b axis.The π-π packing interactions contribute to the formation of a three-dimensional supramolecular architecture.The complex exhibits strong photoluminescence at room temperature.

  17. Spin crossover in iron(II) tris(2-(2 '-pyridyl)benzimidazole) complex monitored by variable temperature methods: synchrotron powder diffraction, DSC, IR spectra, Mössbauer spectra, and magnetic susceptibility (United States)

    Boča, R.; Boča, M.; Ehrenberg, H.; Fuess, H.; Linert, W.; Renz, F.; Svoboda, I.


    The thermal expansion of the spin crossover system [Fe(pybzim) 3](ClO 4) 2 · H 2O (pybzim=2-(2 '-pyridyl)benzimidazole) has been determined from powder X-ray data between 50 and 250 K; the wavelength of the synchrotron source was 1.21888(1) Å. The unit cell parameters of the triclinic crystal system were a=12.091 Å, b=12.225 Å, c=14.083 Å, α=77.70°, β=80.35°, γ=74.35°, and V=1944.9 Å 3 at 250 K. In addition to the linear thermal expansion of the unit cell volume, an extra expansion due to the low-spin (LS) to high-spin (HS) transition is observed. The V( T) function shows a sudden increase comparable with the step in the effective magnetic moment at the transition region (140 K). A similar behavior is obtained on the basis of the infrared spectra. The absorption bands corresponding to the metal-ligand stretching modes change their intensities upon heating: the bands corresponding to the low-spin molecules (at ca. 409, 430, 443, and 460 cm -1) disappear in the gain of the high-spin bands (at 259 and 285 cm -1). The variable-temperature data obtained by different techniques (powder diffraction, EXAFS, IR spectra, Mössbauer spectra, magnetic susceptibility, DSC) have been transformed to a common basis - the temperature dependence of the high-spin mole fraction xHS( T). The application of the Ising-like (two-level) model of the spin crossover led to the thermodynamic data Δ H=2.6 kJ mol -1 and Δ S=19 J K -1 mol -1 as well as to the cooperativeness J/ k≈110 K (subtracted from the susceptibility data) that characterizes the abruptness of the spin crossover in the solid state.

  18. Mixed ligand copper(II) complexes of N,N-bis(benzimidazol-2-ylmethyl)amine (BBA) with diimine co-ligands: efficient chemical nuclease and protease activities and cytotoxicity. (United States)

    Loganathan, Rangasamy; Ramakrishnan, Sethu; Suresh, Eringathodi; Riyasdeen, Anvarbatcha; Akbarsha, Mohamad Abdulkadhar; Palaniandavar, Mallayan


    A series of mononuclear mixed ligand copper(II) complexes [Cu(bba)(diimine)](ClO(4))(2)1-4, where bba is N,N-bis(benzimidazol-2-ylmethyl)amine and diimine is 2,2'-bipyridine (bpy) (1), 1,10-phenanthroline (phen) (2), 5,6-dimethyl-1,10-phenanthroline (5,6-dmp) (3), or dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) (4), have been isolated and characterized by analytical and spectral methods. The coordination geometry around copper(II) in 2 is described as square pyramidal with the two benzimidazole nitrogen atoms of the primary ligand bba and the two nitrogen atoms of phen (2) co-ligand constituting the equatorial plane and the amine nitrogen atom of bba occupying the apical position. In contrast, the two benzimidazole nitrogen atoms and the amine nitrogen atom of bba ligand and one of the two nitrogen atoms of 5,6-dmp constitute the equatorial plane of the trigonal bipyramidal distorted square based pyramidal (TBDSBP) coordination geometry of 3 with the other nitrogen atom of 5,6-dmp occupying the apical position. The structures of 1-4 have been optimized by using the density functional theory (DFT) method at the B3LYP/6-31G(d,p) level. Absorption spectral titrations with Calf Thymus (CT) DNA reveal that the intrinsic DNA binding affinity of the complexes depends upon the diimine co-ligand, dpq (4) > 5,6-dmp (3) > phen (2) > bpy (1). The DNA binding affinity of 4 is higher than 2 revealing that the π-stacking interaction of the dpq ring in between the DNA base pairs with the two bzim moieties of the bba ligand stacked along the DNA surface is more intimate than that of phen. The complex 3 is bound to DNA more strongly than 1 and 2 through strong hydrophobic interaction of the methyl groups on 5,6-positions of the phen ring in the DNA grooves. The extent of the decrease in relative emission intensities of DNA-bound ethidium bromide (EB) upon adding the complexes parallels the trend in DNA binding affinities. The large enhancement in relative viscosity of DNA upon binding

  19. Rapid determination of benzimidazole pesticide in orange juice by liquid chromatography -mass spectrometry%LC-MS快速检测橙汁中苯并咪唑类农药

    Institute of Scientific and Technical Information of China (English)

    姚艳玲; 倪炜华; 顾益


    Objective: A method was established to rapidly determine carbendazim, thiophanate, thiophanate -methyl, 2 - aminobenzimidazole and triabendazole in orange juice by liquid chromatography - mass spectrometry. Methods; The orange juice was diluted with water, and then subjected to solid phase extraction using HLB 3cc cartridge. Then the extract was analyzed by liquid chromatography - mass spectrometry with a mobile phase of water and methanol at a flow rate of 0.20 ml/min. Results: The method showed good linearity in the range of 0.01 mg/L ~ 0. 10 mg/L, the average recoveries of the 5 benzimidazole pesticide in orange juice ranged from 75.0% to 97. 5% , the relative standard deviations ranged from 1. 0% ~ 8. 6% , the limit of detection was from 0. 0046 μg/kg ~ 0.0116 μg/kg. Conclusion; The method was applied to determine carbendazim, thiophanate, thiophanate - methyl, 2 - aminobenzimidazole and triabendazole in orange juice with satisfactory results.%目的:建立液相色谱质谱法快速检测橙汁中多菌灵、硫菌灵、甲基硫菌灵、2-氨基苯并咪唑和噻菌灵5种苯并咪唑类农药的试验方法.方法:样品直接用水稀释后,经HLB 3cc固相萃取柱净化,采用液相色谱质谱仪进行定性、定量分析,以水和甲醇为流动相,在0.20 ml/min下梯度洗脱.结果:该方法在0.01 mg/L~0.10 mg/L范围内呈良好的线性关系,平均回收率为75.0% ~ 97.5%,相对标准偏差为1.0% ~8.6%,检出限为0.0046 μg/kg ~0.0116 μg/kg.结论:该方法适用于橙汁中多菌灵、硫菌灵、甲基硫菌灵、2-氨基苯并咪唑和噻菌灵的检测.

  20. Spin crossover in iron(II) tris(2-(2{sup '}-pyridyl)benzimidazole) complex monitored by variable temperature methods: synchrotron powder diffraction, DSC, IR spectra, Moessbauer spectra, and magnetic susceptibility

    Energy Technology Data Exchange (ETDEWEB)

    Boca, R.; Boca, M.; Ehrenberg, H.; Fuess, H.; Linert, W.; Renz, F.; Svoboda, I


    The thermal expansion of the spin crossover system [Fe(pybzim){sub 3}](ClO{sub 4}){sub 2} {center_dot} H{sub 2}O (pybzim=2-(2{sup '}-pyridyl)benzimidazole) has been determined from powder X-ray data between 50 and 250 K; the wavelength of the synchrotron source was 1.21888(1) A. The unit cell parameters of the triclinic crystal system were a=12.091 A, b=12.225 A, c=14.083 A, {alpha}=77.70 deg., {beta}=80.35 deg., {gamma}=74.35 deg., and V=1944.9 A{sup 3} at 250 K. In addition to the linear thermal expansion of the unit cell volume, an extra expansion due to the low-spin (LS) to high-spin (HS) transition is observed. The V(T) function shows a sudden increase comparable with the step in the effective magnetic moment at the transition region (140 K). A similar behavior is obtained on the basis of the infrared spectra. The absorption bands corresponding to the metal-ligand stretching modes change their intensities upon heating: the bands corresponding to the low-spin molecules (at ca. 409, 430, 443, and 460 cm{sup -1}) disappear in the gain of the high-spin bands (at 259 and 285 cm{sup -1}). The variable-temperature data obtained by different techniques (powder diffraction, EXAFS, IR spectra, Moessbauer spectra, magnetic susceptibility, DSC) have been transformed to a common basis - the temperature dependence of the high-spin mole fraction x{sub HS}(T). The application of the Ising-like (two-level) model of the spin crossover led to the thermodynamic data {delta}H=2.6 kJ mol{sup -1} and {delta}S=19 J K{sup -1} mol{sup -1} as well as to the cooperativeness J/k{approx}110 K (subtracted from the susceptibility data) that characterizes the abruptness of the spin crossover in the solid state.

  1. Primary anti-proliferative activity evaluation of 1-(quinolizidin-1'-yl)methyl- and 1-([Formula: see text]-tert-amino)alkyl-substituted 2-phenyl-, 2-benzyl- and 2-[(benzotriazol-1/2-yl)methyl]benzimidazoles on human cancer cell lines. (United States)

    Tonelli, Michele; Tasso, Bruno; Mina, Lorenzo; Paglietti, Giuseppe; Boido, Vito; Sparatore, Fabio


    Twenty benzimidazole derivatives bearing in position 1 a ([Formula: see text]-tert-amino)alkyl chain (mainly quinolizidin-1-ylmethyl) and in position 2 an aromatic moiety (phenyl, benzyl or benzotriazol-1/2-ylmethyl) were evaluated at the National Cancer Institute (NCI) for anti-proliferative activity against a panel of 60 human cancer cell lines. Four compounds (6, 7, 9 and 10) displayed a large spectrum of activity with [Formula: see text] 10 [Formula: see text] on 24-57 cell lines, while thirteen compounds exhibited sub-micromolar or even nanomolar activity against single cell lines, such as leukemia CCRF-CEM, HL-60 and MOLT-4, CNS cancer SF-268 and, particularly, renal cancer UO-31, sometimes with outstanding selectivity (compounds 5-7, 11, 13 and 18).


    Directory of Open Access Journals (Sweden)

    Ana Carolina Fonseca Lindoso Melo


    Full Text Available Resistance to benzimidazole anthelmintics is reported as an old and persistent problem in many parts of the world. Resistance development depends on the presence of resistance promoters and there are operational, genetic and bioecological factors. The objective of this work was to determine the prevalence of benzimidazole resistance and to study some variables associated with resistance development in small ruminant farms in the Brazilian northeastern semi-arid area. The work was accomplished in 25 sheep and goat farms in Limoeiro do Norte, Palhano, Jaguaruana, Itaiçaba, Aracati, Alto Santo, Morada Nova and Jaguaribe municipalities, in the state of Ceará, Brazil. The procedure used to detect anthelmintic resistant nematodes was the fecal egg count reduction test. In addition, a questionnaire about management practices, infrastructure, anthelmintic usage, flocks sanitary state and veterinary assistance was applied. Data were analyzed using RESO statistical program. The questionnaires were analyzed using Spearman correlation and the simple GLM. In sheep farms, the prevalence of benzimidazole resistance was 88% and in goat farms, it was 87.5%. In sheep and goats farms, Haemonchus spp was the most prevalent genus, followed by Trichostrongylus spp and Oesophagostomum spp. Among variables studied, treatment in the dry season was statistically significant (P = 0.03, pasture rotation was not significant (P = 0.17 but has a predictable value in resistance development.

    KEY WORDS: Associated factors, benzimidazole, Ceará, resistance development.
    A resistência a anti-helmínticos benzimidazóis é relatada como um antigo e persistente problema em diversas partes do mundo. O desenvolvimento da resistência depende da presença de promotores, os quais podem ser fatores operacionais, genéticos e bioecológicos. O objetivo do presente estudo foi determinar a prevalência da resistência a anti-helmínticos benzimidazóis e estudar algumas

  3. 二(1N-苄基-苯并咪唑)二氯合钴配合物的晶体结构、电化学和热稳定性能研究%Structure,Electrochemical and Thermal Stability Investigations of Di (benzyl-benzimidazole-N)dichloro Cobalt (Ⅱ)Complex

    Institute of Scientific and Technical Information of China (English)

    建方方; 肖海连; 孙萍萍


    The title compound, [CoCl2(C7H5N2CH2Ph)2], has been synthesized and structurally characterized by elemental analysis, IR, UV-Vis spectra, TG-DSC and X-ray crystallography. The coordination geometry of each Co atom is formed, by two N atoms from two benzyl-benzimidazole ligands and by two Cl anions, is of a tetrahedron. The data of EA, IR and UV-vis spectra are in good agreement with the result of crystal structure determination. The thermal gravimetry (TG) data indicate that there are four decomposition steps with five endothermic peaks. The final product of the thermal decomposition is Co. The electrochemical properties of the complex was also studied in H2O/DMF solvent by cyclic voltammetry(CV).

  4. Bis[μ-2,2′-dimethyl-1,1′-(3-oxapentane-1,5-diyldi-1H-benzimidazole-κ2N3:N3′]bis[bis(4-methoxybenzoato-κO;κ2O,O′-cobalt(II

    Directory of Open Access Journals (Sweden)

    Lian-Peng Zhao


    Full Text Available The complete molecule of the title complex, [Co2(C8H7O34(C20H22N4O2], is a dimer of the paddle-wheel-type generated by crystallographic inversion symmetry. The CoII ion is pentacoordinated by three O atoms from two 4-methoxybenzoate anions (one bidentate and one monodentate and two N atoms from two 2,2′-bis(2-methyl-1H-benzimidazoleether ligands. This results in a very distorted trigonal–bipyramidal geometry for the metal ion, with both N atoms in equatorial sites. The dihedral angle between the benzimidazole ring systems in the ligand is 60.04 (8°. The configuration of the molecule is supported by intramolecular C—H...O hydrogen bonds.

  5. Crystal structure of poly[[μ-1,1′-(butane-1,4-diylbis(1H-benzimidazole-κ2N3:N3′]{μ-4,4′-[1,4-phenylenebis(oxy]dibenzoato-κ4O,O′:O′′,O′′′}cobalt(II

    Directory of Open Access Journals (Sweden)

    Chen Xie


    Full Text Available In the title compound, [Co(C20H12O6(C18H18N4]n, the CoII atom, located on a twofold rotation axis, is hexacoordinated to four O from two bis-bidentate 4,4′-[phenylenebis(oxy]dibenzoate (L ligands and two N atoms from two 1,1′-(butane-1,4-diylbis(1H-benzimidazole (bbbm ligands, forming a distorted octahedral cis-N2O4 coordination environment. Polymeric zigzag chains along [102] are built up by the bridging L ligands. These chains are additionally connected by the bbbm ligands to produce a two-dimensional coordination polymer parallel too (010.

  6. A novel and orally active poly(ADP-ribose) polymerase inhibitor, KR-33889 [2-[methoxycarbonyl(4-methoxyphenyl) methylsulfanyl]-1H-benzimidazole-4-carboxylic acid amide], attenuates injury in in vitro model of cell death and in vivo model of cardiac ischemia. (United States)

    Oh, Kwang-Seok; Lee, Sunkyung; Yi, Kyu Yang; Seo, Ho Won; Koo, Hyun-Na; Lee, Byung Ho


    Blocking of poly(ADP-ribose) polymerase (PARP)-1 has been expected to protect the heart from ischemia-reperfusion injury. We have recently identified a novel and orally active PARP-1 inhibitor, KR-33889 [2-[methoxycarbonyl(4-methoxyphenyl)-methylsulfanyl]-1H-benzimidazole-4-carboxylic acid amide], and its major metabolite, KR-34285 [2-[carboxy(4-methoxyphenyl)methylsulfanyl]-1H-benzimidazole-4-carboxylic acid amide]. KR-33889 potently inhibited PARP-1 activity with an IC(50) value of 0.52 +/- 0.10 microM. In H9c2 myocardial cells, KR-33889 (0.03-30 microM) showed a resistance to hydrogen peroxide (2 mM)-mediated oxidative insult and significantly attenuated activation of intracellular PARP-1. In anesthetized rats subjected to 30 min of coronary occlusion and 3 h of reperfusion, KR-33889 (0.3-3 mg/kg i.v.) dose-dependently reduced myocardial infarct size. KR-34285, a major metabolite of KR-33889, exerted similar patterns to the parent compound with equi- or weaker potency in the same studies described above. In separate experiments for the therapeutic time window study, KR-33889 (3 mg/kg i.v.) given at preischemia, at reperfusion or in both, in rat models also significantly reduced the myocardial infarction compared with their respective vehicle-treated group. Furthermore, the oral administration of KR-33889 (1-10 mg/kg p.o.) at 1 h before occlusion significantly reduced myocardial injury. The ability of KR-33889 to inhibit PARP in the rat model of ischemic heart was confirmed by immunohistochemical detection of poly(ADP-ribose) activation. These results indicate that the novel PARP inhibitor KR-33889 exerts its cardioprotective effect in in vitro and in vivo studies of myocardial ischemia via potent PARP inhibition and also suggest that KR-33889 could be an attractive therapeutic candidate with oral activity for several cardiovascular disorders, including myocardial infarction.

  7. 基于1-(1′,3′-苯并噁唑-2′-甲基)苯并咪唑的钴(Ⅱ)配合物:晶体结构、弱相互作用和荧光发射光谱%Cobalt(H) Complex Based on 1-(1′ ,3′ -Benzoxazole-2′ -methyl)benzimidazole:Crystal Structure, Weak Interactions and Fluorescent Emission Spectra

    Institute of Scientific and Technical Information of China (English)

    吕世真; 李树娟; 王修光; 柳清湘


    配体1-(1′,3′-苯并恶唑-2′-甲基)苯并咪唑(L)是通过苯并咪唑与2-(氯甲基)-1,3-苯并恶唑烷基化制备而来.配体L与CoCl2·2H2O反应得到了配合物[CoCl2L2] (1).配合物1通过π-π堆积作用和C-H…Cl氢键形成了三维超分子框架结构.测定了L和1的荧光发射光谱.%The ligand 1-(1′,3′-benzoxazole-2′-methyl)benzimidazole (L) was prepared from benzimidazole by alkylation with 2-(chloromethyl)-1,3-benzoxazole.Reaction of ligand L with CoCl2 ·2H2O afforded a complex [CoCl2L2] (1).In complex 1,3D supramolecular frameworks were formed through π-π interactions and C-H…Cl hydrogen bonds.The fluorescence emission spectra of L and 1 are described.CCDC:843658.

  8. 2-(3-甲氧基-4-羟基苯基)苯并咪唑的碳钢海水缓蚀性能%The Corrosion Inhibiton Performance of 2-(3-methoxy-4-hydroxyphenyl) Benzimidazole for Carbon Steel in Saltwater

    Institute of Scientific and Technical Information of China (English)

    茌方; 周桃玉


    本文研究合成了样品2-(3-甲氧基-4-羟基苯基)苯并咪唑(BID),并采用傅立叶红外光谱(FT-IR)和紫外光谱对其进行了表征。同时,采用电化学极化曲线(EPC)、交流阻抗谱(EIS)和腐蚀失重法测试了BID的缓蚀效果。结果表明,BID在3.5%NaCl溶液中对Q235碳钢有约75%的缓蚀效果,腐蚀速率降至0.115mm/a,其作用效果为阳极抑制型。%In this paper, 2-(3-methoxy-4-hydroxyphenyl)benzimidazole(BID) is synthesized and characterized by Fourier transform infrared spectroscopy(FT-IR) and ultraviolet spectroscopy. Its corrosion inhibition performance is investigated by electrochemical polarization curves(EPC), electrochemical impedance spectroscopy(EIS) and weight loss methods. The results show that, with the presence of BID in 3.5%NaCl solution, the corrosion rate of Q235 steel dropped to 0.115mm/a and inhibition efficiency reaches to about 75%, which act as anodic type inhibitor in saltwater solution.

  9. Poly(imide benzimidazole)s for high temperature polymer electrolyte membrane fuel cells

    DEFF Research Database (Denmark)

    Yuan, Sen; Guo, Xiaoxia; Aili, David


    is an order of magnitude higher than that of the common polybenzimidazole membranes with similar acid contents. A preliminary H2/air fuel cell test at 180°C showed a peak power density of 350mWcm-2 of the fuel cell equipped with the phosphoric acid doped PIBI-1/1 membrane with a 300wt% acid uptake......, demonstrating the technical feasibility of the novel electrolyte materials. © 2013 Elsevier B.V....

  10. Acetylene- and Phenylacetylene-Terminated Poly(Arylene Ether Benzimidazole)s (PAEBI's) (United States)

    Connell, John W.; Hergenrother, Paul M.; Smith, Joseph G., Jr.


    Polymers prepared by first synthesizing polymers terminated with hydroxy groups, then reacting them with either 4-ethynylbenzoyl chloride or 4-fluoro-4'-phenylethynylbenzophenone. Endcapped polymers thermally cured to yield materials with attractive combination of properties. Cured acetylene-and phenylacetylene-terminated PAEBI's exhibit higher glass-transition temperatures and better retention of mechanical properties at high temperatures. Cured acetylene- and phenylacetylene-terminated polymers exhibit excellent adhesion to copper foil and polyimide film. Potentially useful as adhesives, coatings, composite matrices, fibers, films, membranes, and moldings.

  11. Pharmacokinetics of Three Benzimidazoles Suspended in Oleic Acid,Soybean Oil or 1% Tragacanth,and Administered Orally to Mice at A Single Dose%小鼠口服3种苯并咪唑类药物的油酸、大豆油和1%西黄耆胶混悬剂的药动学

    Institute of Scientific and Technical Information of China (English)

    姜斌; 张皓冰; 刘丛珊; 陶奕


    OBJECTIVE To determine the pharmacokinetics of three benzimidazoles ( albendazole, fenbendazole and fluben-dazole) suspended in three different media [oleic acid, soybean oil or 1% tragacanth (served as control) ] in mice, and observe the correlation of those pharmacokinetic parameters with the solubilities of the three benzimidazoles in corresponding medium. METHODS Albendazole, fenbendazole and flubendazole suspened in oleic acid, soybean oil or 1% tragacanth were prepared by ball grinding mill. Groups of 45 - 54 mice were administered orally with one of aforementioned benzimidazole suspensions at a single dose of 100 mg·kg-1 ( albendazole) or 50 mg·kg-1 (fenbendazole and flubendazole). Subgroups with 5-6 mice in each group were bled at varying intervals within 24 h. Plasma was then separated from heparin-anticoagulated blood, and evaluated for the presence of the drug by high performance liquid chromatography ( HPLC ). Pharmacokinetic parameters of each drug were calculated using DAS ( Drug AnaLyze System). RESULTS After oral administration of three benzimidazoles suspended in oleic acid, soybean oil or 1% tragacanth, the pharmacokinetic parameters of each drug were described as follows; albendazole, the MRT (average retention time) were (3. 91 ± 0.29), (3.70±0.09) and (1. 59 ± 0. 14) h, ρmax (maximum concentration) were (0.66±0.08), (0.29±0.05) and (0. 34±0. 09) mg·L-1 , AUC (area under the concentration-time curve) were (3. 19 ±0.40) , (1. 25 ±0.09) and (0. 50 ±0. 05) mg·L·h-1, F (relative bioavailability, the AUC compared with that of 1% tragacanth group) were 6. 38 and 2. 50; fenbendazole, the MRT were (5. 72 ±0. 14) , (4. 83 ±0.38) and (3. 85 ±0.25) h, ρmax were( 0. 70 ± 0. 11) , (0.20 ±0.05) and (0. 12 ±0.03) mg·L-1 , AUC were (5. 02 ±0.73) , (1.08 ±0.21) and (0.52 ±0.07) mg·h·L-1 , F were 9.65 and 2.08; flubendazole, the MRT were (5.71 ±0.37), (4.59±0.39) and (3. 34 ±0.20) h, pmax were (0.93 ±0. 14), (0.58 ±0.09) and (0

  12. Investigation of Excited-State Proton Transfer of 2-(3-Acetamido-2-pyridyl)benzimidazole in the Confined Nanocavity of Cucurbit[7]uril%七元瓜环纳米腔限制环境下2-(3-乙酰胺基-2-吡啶基)苯并咪唑的激发态质子转移

    Institute of Scientific and Technical Information of China (English)

    易平贵; 阳习春; 刘金; 侯博; 于贤勇; 李筱芳; 汪朝旭; 郑柏树


    The interaction of2-(3-acetamido-2-pyridyl)-benzimidazole (2-3Am2PyBI) with cucurbit[7]uril (CB7) macrocycle and the effect of inclusion on the proton transfer of 2-3Am2PyBI were studied by using emission fluorescence,1H NMR spectra and quantum chemical calculation.By the way,the proton transfer of the dye with and without acetyl (2-3A2PyBI) was also studied.The results indicate that the acetyl promoted the process of proton transfer of the benzimidazole and the cationic form binds with CB7 easier than the other forms of the dye.The fluorescence studying at selected pHs suggest that the proton transfer process of the dye was retarded by interacting with CB7 nanocavity and the molar rate is host ∶ guest=1 ∶ 1 analyzed by the Benesi-Hildebrand method.The dye entered into the CB7 cavity with its benzene ring was proved by the 1H NMR titration experiment and the protonated forms were verified by the quantum calculation with fluorescence spectra.%以荧光发射光谱,1H NMR谱及量子化学计算研究了2-(3-乙酰胺基-2-吡啶基)苯并咪唑(2-3Am2PyBI)质子转移过程及其与七元瓜环超分子(CB7)的包合作用,考察了乙酰基取代基效应及CB7的包合作用对2-3Am2PyBI质子转移过程的影响.结果表明:乙酰基取代促进了质子转移过程;2-3Am2PyBI阳离子构型更易与CB7发生包合作用;在特定溶液pH值条件下,摩尔比法荧光光谱实验表明超分子包合作用抑制了2-3Am2PyBI的激发态质子转移过程;Benesi-Hildebrand方程拟合得到,超分子体系的包合比为1∶1;1H NMR测试进一步表明2-3Am2PyBI以苯环部分进入CB7的空腔,同时,以量化计算与荧光实验结合,从理论与实验方面共同验证了2-3Am2PyBI的质子转移异构体.

  13. Conjugation of organoruthenium(II) 3-(1H-benzimidazol-2-yl)pyrazolo[3,4-b]pyridines and indolo[3,2-d]benzazepines to recombinant human serum albumin: a strategy to enhance cytotoxicity in cancer cells. (United States)

    Stepanenko, Iryna N; Casini, Angela; Edafe, Fabio; Novak, Maria S; Arion, Vladimir B; Dyson, Paul J; Jakupec, Michael A; Keppler, Bernhard K


    Following our strategy of coupling cyclin-dependent kinase (Cdk) inhibitors with organometallic moieties to improve their physicochemical properties and bioavailability, five organoruthenium complexes (1c-5c) of the general formula [RuCl(η(6)-arene)(L)]Cl have been synthesized in which the arene is 4-formylphenoxyacetyl-η(6)-benzylamide and L is a Cdk inhibitor [3-(1H-benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines (L1-L3) and indolo[3,2-d]benzazepines (L4 and L5)]. All of the compounds were characterized by spectroscopic and analytical methods. Upon prolonged standing (2-3 months) at room temperature, the dimethyl sulfoxide (DMSO) solutions of 1c and 2c(-HCl) afforded residues, which after recrystallization from EtOH and EtOH/H(2)O, respectively, were shown by X-ray diffraction to be cis,cis-[Ru(II)Cl(2)(DMSO)(2)(L1)]·H(2)O and mer-[Ru(II)Cl(DMSO)(3)(L2-H)]·H(2)O. Compound 5c, with a coordinated amidine unit, undergoes E/Z isomerization in solution. The antiproliferative activities and effects on the cell cycle of the new compounds were evaluated. Complexes 1c-5c are moderately cytotoxic to cancer cells (CH1, SW480, A549, A2780, and A2780cisR cell lines). Therefore, in order to improve their antiproliferative effects, as well as their drug targeting and delivery to cancer cells, 1c-5c were conjugated to recombinant human serum albumin, potentially exploiting the so-called "enhanced permeability and retention" effect that results in the accumulation of macromolecules in tumors. Notably, a marked increase in cytotoxicity of the albumin conjugates was observed in all cases.

  14. Crystal structure, ferromagnetostructural behavior and evidence of cooperative Jahn-Teller interactions of the complex [CuL]Cl·H 2O (L= N-glycyl-2(aminomethyl)benzimidazol), synthesized by a novel simple method of peptide bond formation. (United States)

    García-Orozco, Ivan; Tapia-Benavides, Antonio Rafael; Alvarez-Toledano, Cecilio; Toscano, Ruben A.; Ramírez-Rosales, Daniel; Zamorano-Ulloa, Rafael; Reyes-Ortega, Yasmi


    [CuL]Cl·H 2O 1 (L= N-glycyl-2(aminomethyl)benzimidazol) compound crystallizes in the orthorhombic space group Pna2 1 with unit cell parameters a=7.140(5) Å, b=17.621(5) Å, c=9.941(5) Å. Its structure shows that the copper(II) ion is tetra coordinated with a square planar geometry. The ligand acts as a tridentate and the chloride ion is the fourth ligand. Symmetry related units stack into helicoidal columns along the ā direction producing weakly bonded strips with dihedral angles of 2.6° between two consecutive molecular planes. UV/VIS spectrum of 1 shows one broad and weak band at 622 nm, characteristic of d-d transitions, indicative of low local Cu(II) symmetry. X band ESR spectra of 1 at 300 and 77 K are axial exchange narrow lines with g∥=2.135 and g⊥=2.028. However, the axial spectrum at 6.4 K shows an increment Δ g∥=0.076(6) and Δ g⊥=0.028(4) which suggests a cooperative Jahn-Teller interactions between complexes via the hydrogen-bonding network. Magnetic susceptibility data at 18-300 K and fitted to the modified Bleany-Bowers equation indicate a weak ferromagnetic coupling with 2J≅+17 cm-1, which is compatible with the helium temperature ESR results and with the helicoidal stacking into columns of the molecules along the a-axis with 78.9° Cu'-Cl'-Cu and 81.2° Cu'-N( 1)-Cu bonds angles. The synthesis is a novel, simple and efficient method: in aqueous conditions and heterogeneous phase with basic copper(II) carbonate, which carries out the formation of the stable peptide bond.

  15. (2-(4'-噻唑基)苯并咪唑)(L-丙氨酸根)铜(Ⅱ)配合物的合成、表征、抑菌活性及与DNA的作用%Synthesis, Characterization, Antibacterial Activities and DNA Interaction of Ternary Copper(Ⅱ) Complex with 2-(4'-Thiazolyl) Benzimidazole and L-Alaninate

    Institute of Scientific and Technical Information of China (English)

    朱丽; 卢艳梅; 区志镔; 乐学义


    合成了新的三元铜(Ⅱ)配合物:[Cu(TBZ)(L-Ala)(H2O)] ClO4[其中,TBZ =2-(4'-噻唑基)苯并咪唑,L-Ala=L-丙氨酸根].通过元素分析、摩尔电导率、红外光谱及电子吸收光谱对该配合物进行了表征.用试管二倍稀释法研究了配合物的抗菌活性,发现配合物对金黄色葡萄球菌Staphylococcus aureus(C+)、枯草杆菌Bacillus subtilis(G+)、沙门氏杆菌Salmonella typhi(G-)和大肠埃希菌Escherichia coil(G-)具有良好的抑制作用.另外,采用电子吸收光谱、荧光光谱、圆二色光谱、粘度测定及琼脂凝胶电泳方法研究了配合物与小牛胸腺DNA(CT-DNA)的作用.结果表明,配合物可能以插入方式与CT-DNA作用,在维生素C存在下通过羟自由基(·OH),单线态氧(1O2)或者1O2类似物切割pBR322 DNA双螺旋结构.%A new ternary copper( II ) complex; [Cu(TBZ) ( L- Ala) ( H2 O) ] C1O4 [ TBZ = 2-(4'-thia-zolyl) benzimidazole, L-Ala = L-alaninate] , was synthesized and characterized by elemental analysis, molar conductivity, infrared absorption spectrum, and electronic absorption spectrum. The complex was assayed against gram-positive ( Staphylococcus aureus, Bacillus subtilis ) and gram-negative ( Salmonella typhi, Escherichia coil) bacteria by double dilution method, and the interaction of the complex to DNA was investigated by electronic absorption spectrometry, fluorescence spectrometry, CD spectrometry, viscosity measurement and agarose gel electrophoresis. The results indicated that the complex had good antibacterial activity, which could be bound to CT-DNA ( calf thymus DNA) by intercalative mode, cleave pBR322 DNA in the presence of vitamin C in the involvement of the hydroxyl radical, and possibly singlet oxygen.

  16. Synthesis, Structure and Geometrical Calculation of a Novel Co-crystal of {[4-Bromo-2-(benzimidazol-2-yl)phenolato][2- (1-butylbenzimidazol-2-yl)phenolato]zinc(Ⅱ)] and Bis[μ-2- (1- butylbenzimidazol-2-yl)phenolato]- 1κN3: 2κO; 1κO:2κN3-bis{[2-(1-butylbenzimidazol-2-yl)phenolato-κ2N3,O]zinc(Ⅱ)}

    Institute of Scientific and Technical Information of China (English)

    TONG Yi-Ping


    The title compound has been synthesized and characterized crystallographically. It is a co-crystal consisting of two different neutral zinc(Ⅱ) complexes with Hbpbm (Hbpbm = 4-bromo-2-(benzimidazol-2-yl)phenol) and Hnpbm (Hnpbm = 2-(1-butylbenzimidazol-2-yl)phenol).One is a monomeric mixed-ligand complex of [Zn(bpbm)(npbm)] 1 and the other a dimer of[Zn2(npbm)4] 2 with their ratio of 2:1. Thus the overall formula for the title compound is 21·2.Adjacent 1 and 2 are connected to each other by intermolecular hydrogen bonding interactions in the lattice. The crystal data: monoclinic, space group P21/c, a= 15.0141(12), b = 20.9941(17), c =18.4686(15) (A), β = 97.445(2)°, V= 5772.4(8) (A)3, Mr= 2429.68, Z = 2, Dc = 1.398 g/cm3,μ = 1.579mm-1, F(000) = 2504, R = 0.0637 and wR = 0.1771 for 6464 observed reflections (I> 2σ(Ⅰ)). The geometrical structure for 1 has also been theoretically optimized and compared with the experimental one.

  17. Synthesis and Crystal Structure of Eu(Ⅲ)/Dy(Ⅲ) Coordination Polymers with Benzimidazole-5,6-dicarboxylate Acid%铕(Ⅲ)/镝(Ⅲ)苯并咪唑-5,6-二羧酸配位聚合物的合成和晶体结构

    Institute of Scientific and Technical Information of China (English)

    董丽娜; 马雪; 查玉娥; 李夏


    The complexes {[Ln(Hbidc)(bidc)(H2O)3]-3H2O}n (Ln=Eu 1, Dy 2; H2bidc=benzimidazole-5,6-dicarboxylic acid)have been obtained by hydrothermal method and characterized by X-ray single-crystal diffraction. The two complexes belong to monoclinic system, Plxk space group. Complexes 1 and 2 have similar ID chain structures. Ln3+ ion is nine-coordinated by six oxygen atoms of carboxylate groups and three oxygen atom of water molecules. Ln3+ ions are linked by bmdc ligands to form a ID helical chain. The right- and left-handed chains are further connected to form 3D network via interchain hydrogen bonds and tt-77 stacking interactions. The two complexes behave characteristic fluorescence of Eu3+ and Dy3* ions, respectively. CCDC: 883519, 1; 883518, 2.%水热法合成了配合物{[Ln(Hbmdc)(bmdc)(H2O)3]·3H2O}n(Ln=Eu,1;Dy,2;H2bmdc=苯并咪唑-5,6-二羧酸),用X-射线单晶衍射分析确定了配合物的晶体结构.配合物为单斜晶系,P21/c空间群.配合物1和2具有相似的一维链状结构.配体H2bmdc以2种不同的类型与Ln3+离子配位:完全去质子化的bmdc配体和咪唑环上的氮原子被质子化的Hbmdc配体.bmdc配体的2个羧基采取双齿螯合/双齿螯合方式配位;Hbmdc配体的1个羧基采取双齿螯合方式配位,另1个羧基未参与配位.每个Ln3+离子与6个羧基氧原子和3个水分子中氧原子配位,形成9配位的扭曲单帽四方反棱柱体.相邻的Ln3+离子通过bmdc配体桥联形成螺旋链状结构.链和链之间通过π-π堆积和氢键进一步连接成三维超分子结构.配合物1和2分别显示Eu3+和Dy3+离子的特征荧光.

  18. 2-Methyl-1H-benzimidazol-3-ium hydrogen phthalate

    Directory of Open Access Journals (Sweden)

    YuanQi Yu


    Full Text Available The asymmetric unit of the title compound, C8H9N2+·C8H5O4−, contains two independent ion pairs. In each 2-methyl-1H-benzimidazolium ion, an intramolecular O—H...O bond forms an S(7 graph-set motif. In the crystal, the components are linked by N—H...O hydrogen bonds, forming chains along [210]. Further stabilization is provided by weak C—H...O hydrogen bonds.

  19. 2-(1H-Benzimidazol-2-ylphenol

    Directory of Open Access Journals (Sweden)

    S. M. Prakash


    Full Text Available The title molecule, C13H10N2O, is essentially planar, the maximum deviation from the plane of the non-H atoms being 0.016 (2 Å. The imidazole ring makes a dihedral angle of 0.37 (13° with the attached benzene ring. An intramolecular O—H...N hydrogen bond generates an S(6 ring motif. In the crystal, molecules are linked through N—H...O hydrogen bonds, forming chains propagating in [001]. The crystal packing also features four π–π stacking interactions involving the imidazole ring, fused benzene ring and attached benzene ring system [centroid–centroid distances = 3.6106 (17, 3.6108 (17, 3.6666 (17 and 3.6668 (17 Å].

  20. Glucogeno sintasa en helmintos parasitos: inhibicion por benzimidazoles


    H. Gomez-Banqueri; Garcia Ruiz,M. A.; M. Monteoliva; Sanchez-Moreno, M


    Se ha determinado el effecto inhibidor sobre la actividad Glucogeno sintetasa (E.C.2.41.11) por parte de cuatro antihelminticos: Albendazol, Mebendazol, Parbendazol y Tiabendazol. Observandose que en todos los casos, es el Parbendazol quien ha demostrado un mayor poder inhibidor sobre la glucógeno sintetasa de Ascaris suum, Fasciola hepatica y Moniezia expansa. El Tiabendazol es el anti-helmintico que menor efecto inhibidor ha presentado sobre la enzima en los tres parasitos objeto de nuestro...

  1. Glucogeno sintasa en helmintos parasitos: inhibicion por benzimidazoles

    Directory of Open Access Journals (Sweden)

    H. Gomez-Banqueri


    Full Text Available Se ha determinado el effecto inhibidor sobre la actividad Glucogeno sintetasa (E.C.2.41.11 por parte de cuatro antihelminticos: Albendazol, Mebendazol, Parbendazol y Tiabendazol. Observandose que en todos los casos, es el Parbendazol quien ha demostrado un mayor poder inhibidor sobre la glucógeno sintetasa de Ascaris suum, Fasciola hepatica y Moniezia expansa. El Tiabendazol es el anti-helmintico que menor efecto inhibidor ha presentado sobre la enzima en los tres parasitos objeto de nuestro estudio. Con el presente trabajo y otros previstos en la misma linea, se pretende aportar nuevos datos acerca del aun desconocido locus de acción de estos antihelminticos.

  2. 1-Methyl-2-methylsulfanyl-6-nitro-1H-benzimidazole

    Directory of Open Access Journals (Sweden)

    Mohamed El Ghozlani


    Full Text Available The molecule of the title compound, C9H9N3O2S, is built up from fused five- and six-membered rings connected to methylsulfanyl and nitro groups, respectively. The mean plane through the fused ring system is inclined slightly relative to the plane passing through the nitro group [dihedral angle = 3.6 (2°]. In the crystal, molecules are linked by C—H...O hydrogen bonds and π–π interactions between imidazole rings [inter-centroid distance = 3.667 (3 Å], forming a three-dimensional network.

  3. Synthesis and evaluation of benzimidazole derivatives as poly(ADP-ribose) polymerase inhibitors%苯并咪唑类聚腺苷二磷酸核糖聚合酶抑制剂的合成及初步活性研究

    Institute of Scientific and Technical Information of China (English)

    沈超; 王慧源; 柳军; 赵娜; 张陆勇; 吴晓明; 孙宏斌


    Poly (ADP-ribose) polymerases(PARPs) are a large enzyme family which consists of at least 17 members. These enzymes are implicated in multiple cellular processes through catalysis of the addition of ADP-ribose polymers on various acceptor proteins. PARP-1, the most abundant isoform which can be activated by DNA damage,plays an important role in the repair of DNA single strand breaks(SSBs) under normal circumstances. However,PARP-1 can also contribute to resistance after cancer therapy due to its DNA repair activity. Thus PARP inhibitors have been pursued for many years as chemo/radiotherapy sensitizers in cancer treatment. Besides being used in combination, PARP inhibitors may also be applied as monotherapy in some specific cancer types with synthetic lethality as the main mechanism of action. There are currently at least six compounds being investigated in clinical trials,including BSI201 ,AZD2281, ABT888, MK4827, AG014699,and INO1001. NU1085 ,developed by the University of Newcastle,has been used as a benchmark of PARP inhibitors due to its potent activity and other good features. We used NU1085 as the lead compound,attempting to find more desirable PARP inhibitors through structural modification. Docking between PARP-1 and the designed molecules showed that introduction of lipid soluble groups at 4'-position might improve the PARP inhibitory activity. In addition, a series of 4-carborsylate derivatives were also designed and synthesized to find novel PARP inhibitors. Twenty-two benzimidazole derivatives were synthesized in all, starting with 3-nitrophthalic anhydride which underwent ring-opening, Hofmann rearrangement, amidation or esterification,and reduction to give diamino compounds. Condensation of the diamino compounds with benzaldehyde or its derivatives afforded the target compounds. All the target compounds were structurally confirmed by 1H-NMR, IR and MS and seventeen compounds were novel ones. The following poly (ADP-ribose) polymerase inhibitory

  4. Structure, Antibacterial Activities and DNA Cleavage of a Copper(Ⅱ) Complex with 2-(2'-Pyridyl)benzimidazole and L-Alaninate%(2-(2'-吡啶)苯并咪唑)(L-丙氨酸根)铜(Ⅱ)配合物结构、抗菌活性及DNA断裂作用

    Institute of Scientific and Technical Information of China (English)

    卢艳梅; 区志镔; 胡伟; 乐学义


    设计合成了新的(2-(2'-吡啶)苯并咪唑)(L-丙氨酸根)铜(II)配合物:[Cu(HPB)(L-Ala)(ClO4)(H2O)]2 H2O[HPB=2-(2'-吡啶)苯并咪唑,L-Ala=L-丙氨酸根].应用元素分析、红外光谱、紫外可见光谱、摩尔电导率、电喷雾质谱及X射线单晶衍射等方法对配合物的组成及结构进行了表征.该配合物晶体属单斜晶系,P21空间群,晶胞参数:a=1.1900(2)nm,b=0.80500(16)nm,c=1.9700(4)nm,β=94.78(3)°,Z=2,Dc=1.672 g cm-3,F(000)=968,残差因子R1=0.0427,wR2=0.1106[I〉2σ(I)],S=0.999.在配合物分子中,2-(2'-吡啶)苯并咪唑和L-丙氨酸根以双齿配位方式在分子平面上与中心铜(II)离子配位,而水分子及高氯酸根单齿弱配位于分子轴向上,构成了一拉长的八面体结构.利用二倍试管稀释法测定了配合物的抗菌活性,并且研究了配合物对pBR 322 DNA的断裂作用.结果表明,该配合物对枯草杆菌(B.subtilis,G+),金黄色葡萄球菌(S.aureus,G+),大肠杆菌(E.coil,G-)和沙门氏杆菌(Salmonella,G-)具有良好的抑制活性,最小抑菌浓度为50~80μg mL-1,在维生素C存在下能够通过羟基自由基OH氧化断裂pBR 322 DNA双螺旋结构.%A new copper(II) complex: [Cu(HPB)(L-Ala)(ClO4)(H2O)]2 H2O [HPB = 2-(2'-pyridyl) benzimidazole,L-Ala=L-alaninate],was synthesized and characterized by elemental analysis,IR,UV-Vis,molar conductivity,ES-MS and single crystal X-ray diffraction.The crystal belongs to the monoclinic space group P21,with the crystal cell parameters: a=1.1900(2) nm,b=0.80500(16) nm,c=1.9700(4) nm,β= 94.78(3)°,Z=2,Dc=1.672 g cm-3,F(000)=968,residual factors R1=0.0427,wR2=0.1106 [I2σ(I)],S =0.999.The central Cu(II) ions for the complex show a distorted and elongated octahedral geometry in which two nitrogens of HPB and the carboxylate oxygen atom O and the amino nitrogen

  5. Superoxide dismutase from Trichuris ovis, inhibiton by benzimidazoles and pyrimidine derivatives

    Directory of Open Access Journals (Sweden)

    M. Sanchez-Moreno


    Full Text Available Three superoxide dismutase isoenzymes of different cellular location were detected in an homogenate of Thrichuris ovis. Each of these molecular forms was purified by differential centrifugation and precipitation with ammonium sulphate, followed by chromatography on DEAE-cellulose and Sephadex G-75 columns. The activity levels of the two molecular forms detected in the mitochondrial (one cyanide sensitive Cu-Zn-SOD and the other cyanide intensitive Mn-Sod were higher than that of the superoxide dismutase detected in the cytoplasmic fraction (cyanid sensitive Cu-Zn-SOD. All the mollecular forms present evident differences to the SODs contained in the host liver. Molecular mass and some of the physical and chemical aproperties of the enzyme was determined for all three molecular forms. An inhibitory effect on the SOD of the parasite an the host was detected with a series of compounds, some of wich markedly inhibited parasite ensyme but not host enzyme.

  6. Alkali doped poly (2,5-benzimidazole) membrane for alkaline water electrolysis: Characterization and performance (United States)

    Diaz, Liliana A.; Hnát, Jaromír; Heredia, Nayra; Bruno, Mariano M.; Viva, Federico A.; Paidar, Martin; Corti, Horacio R.; Bouzek, Karel; Abuin, Graciela C.


    The properties and performance of linear and cross-linked KOH doped ABPBI membranes as electrolyte/separator for zero gap alkaline water electrolysis cells are evaluated and compared with a commercial Zirfon® diaphragm. Stability in alkaline environment, swelling, thermal properties, water sorption, KOH uptake and conductivity of linear (L-ABPBI) and cross-linked (C-ABPBI) membranes doped with different concentrations of KOH are analyzed. Linear membranes show stability up to 3.0 mol·dm-3 KOH doping, while cross-linked membranes are stable up to 4.2 mol·dm-3 KOH doping. Both kinds of membranes exhibit good thermal stability and reasonable specific ionic conductivity at 22 °C in the range between 7 and 25 mS·cm-1, being slightly higher the conductivity of C-ABPBI membranes than that of L-ABPBI ones. In short-term electrolysis tests both L-ABPBI and C-ABPBI membranes show better performance than Zirfon diaphragm in the range from 50 to 70 °C. A current density of 335 mA·cm-2 at a cell voltage of 2.0 V is attained with C-ABPBI membranes doped in 3 mol·dm-3 KOH at 70 °C, a performance comparable with that of commercial units operating at temperatures ca. 80 °C and 30 wt% KOH (6.7 mol·dm-3) as electrolyte.

  7. Sensitization of radiation (UV and gamma) induced DNA damage by halogenated bi-benzimidazole derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Petronella, N. [The University of Melbourne, Parkville, VIC (Australia). Department of Chemistry]|[Peter McCallum Cancer Institute, Melbourne, VIC (Australia); Cooper, R. [The University of Melbourne, Parkville, VIC (Australia). Department of Chemistry; Martin, R.F. [Peter McCallum Cancer Institute, Melbourne, VIC (Australia)


    Full text: In this study, an investigation was made into the photochemistry and radiation chemistry of ortho-Iodo Hoechst and meta-Iodo Hoechst. These compounds are related to the commercially available dye Hoechst 33258 and are being developed for potential use as radiosensitizers. An efficiency estimate of the number of dehalogenation events required to generate a DNA strand break was determined by quantitating relative yields of DNA strand breakage and ligand dehalogenation. DNA damage was assayed by agarose gel electrophoresis. A method was developed to separate reaction products from DNA after irradiation so that reaction products could be identified and dehalogenation quantitated by HPLC. From steady state photolysis investigations under aqueous conditions it was determined that there is a ten fold difference in quantum efficiency for the DNA strand breakage process. This is due to ortho-Iodo Hoechst having a ten times greater quantum yield of dehalogenation than meta-Iodo Hoechst. Thus it is interesting to note that both compounds require the same number of radical species to generate a DNA strand break. The addition of ethanol (a radical scavenger) to the solvent system, reduces: (1) yields of dehalogenation, (2) yields of DNA strand breakage and (3) the DNA strand breakage efficiencies of both analogues. However unlike the aqueous situation, in the presence of a radical scavenger the radical generated from ortho-Iodo Hoechst is more efficient than the meta-Iodo Hoechst generated radical at attacking and damaging DNA. Thus the radical generated from meta-Iodo Hoechst is more susceptible to interference from a radical scavenger than the ortho-Iodo Hoechst based radical. Steady state gamma radiolysis investigations have found that sensitization is only observed for ortho-Iodo Hoechst in a solvent system where hydroxyl radicals are scavenged by ethanol. The addition of e{sup -}{sub (aq)} scavengers (nitrate and oxygen) have demonstrated that sensitization is mediated by electron capture. Good yields of dehalogenation were observed for both compounds. However the inability of meta-Iodo Hoechst to be a sensitizer is believed to be related to the susceptibility of meta-Iodo Hoechst to interference from radical scavengers

  8. Synthesis and evaluation of benzimidazole derivatives as selective COX-2 inhibitors. (United States)

    Rathore, Ankita; Mujeeb-Ur-Rahman; Siddiqui, Anees A; Ali, Abuzer; Yar, Mohammad Shahar


    A new series of 1-{(5-substituted-alkyl/aryl-1,3,4-oxadiazol-2-yl)methyl}-2-(piperidin-1-ylmethyl)-1Hbenzimidazoles (5a-5r) was synthesized and screened for their inhibitory activity against COX (1 and 2). In vivo antiinflammatory activity of potent compounds was done by carrageenan-induced rat paw edema model. In vitro anticancer activity of synthesized compounds was also performed at the National Cancer Institute (NCI) against NCI 60 cell lines panel. Out of the 18 compounds screened, 5h, 5i, 5j and 5l were found to be potent COX-2 inhibitors in the range of IC50 0.06-0.81 μM. In vivo anti-inflammatory screening results revealed that the compounds 5h and 5j manifested profound percent protection of 72.8 and 75.0%, respectively. Compound 5f exhibited moderate cytotoxicity with 58.79% growth inhibition against SNB-75 (CNS Cancer) cell lines and moderate activity against COX-2 (IC50 = 8.0 μM).

  9. Design, synthesis and computational validation of novel benzimidazole/indole-based PPARα and PPARγ partial agonists

    Indian Academy of Sciences (India)

    Raman K Verma; Prithwish Ghosh; Vijay Kumar; Lalit K Wadhwa


    The design and synthesis of benzimidazolyl and indolyl linked -alkoxy phenylpropanoic acid derivatives and the -keto ester analogues in an effort to develop novel peroxisome proliferator activated receptors ligands expected to exhibit PPAR and PPAR partial agonism in the management of hyperglycemia and hyperlipidemia for the treatment of type 2 diabetes is reported. Computational validation of the designed molecules through activity prediction and docking studies showed expected results.

  10. Benzimidazole as Novel Therapy for Hormone-Refractory Metastatic Prostate Cancer (United States)


    directly into a single tibia of immunocompromised mice via intraosseous injection. When bone lesions were confirmed to be growing via bioluminescent...3MLN4 cells were generated by intraosseous injection into the tibia of mice, before treatment with vehicle or 100 mg/kg albendazole (ABZ), given...generated by intraosseous injection into the tibia of mice, before treatment with vehicle or 100 mg/kg albendazole, three times a week for two weeks

  11. Resistência a benzimidazóis por Guignardia citricarpa Guignardia citricarpa resistance to benzimidazoles

    Directory of Open Access Journals (Sweden)

    Maria Beatriz Calderan Rodrigues


    Full Text Available O objetivo deste trabalho foi avaliar a resistência de Guignardia citricarpa aos fungicidas carbendazim e piraclostrobina, por meio de avaliação do crescimento em meio de cultura, decomposição de tecido foliar e produção de corpos de frutificação. Para isso, o fungo G. citricarpa foi isolado de lesões de frutos de laranja (Citrus sinensis, produzidos em área com intensa aplicação de fungicida. Os isolados obtidos foram avaliados quanto à sensibilidade aos fungicidas piraclostrobina e carbendazim, nas dosagens de 0,5, 1 e 2 µg mL-1 de i.a., para se verificar o efeito da pressão de seleção causada pelo uso destes compostos em áreas citrícolas. Embora tenha sido observada redução efetiva no número de estruturas reprodutivas e na decomposição de folhas e frutos infectados com G. citricarpa, após a aplicação dos fungicidas, 7,5% dos isolados avaliados sobre meio de cultura apresentaram resistência a esse fungicida, o que indica que pode ocorrer seleção de isolados resistentes no campo. Para a piraclostrobina não foi observada resistência, o que indica que pode ser um composto alternativo para ser utilizado de forma alternada com carbendazim, para diminuir as chances de ocorrência de resistência do patógeno.The objective of this work was to evaluate the resistance of Guignardia citricarpa to pyraclostrobine and carbendazim fungicides, through: growth analysis in culture media amended with the fungicides; leaf decomposition; and production of reproductive structures on leaves naturally infected with these fungi. G. citricarpa was isolated from symptomatic fruits of sweet orange (Citrus sinensis cultivated in area with intense fungicide application. The sensibility to fungicides of G. citricarpa isolates was evaluated with pyraclostrobine and carbendazim, in the doses 0.5, 1 e 2 µg mL-1 a.i., to verify the effect of selection pressure caused by continuous use of these compounds. Although, reduction on leaf decomposition and on the number of reproductive structures were observed after application of pyraclostrobine and carbendazim, 7.5% of the isolates, evaluated in culture media, exhibited resistance to carbendazim, suggesting that the use of this agrochemical must be combined to other active principles in a consortium to reduce the chances of resistance occurrence. No resistance to pyraclostrobine was observed among tested isolates, what indicates that this could be an alternative compound to be used in combination to carbendazim, to minimize the chance of resistance occurrence.

  12. Construction and screening of 2-aryl benzimidazole library identifies a new antifouling and antifungal agent.

    Digital Repository Service at National Institute of Oceanography (India)

    Majik, M.S.; Tilvi, S.; Mascarenhas, S.; Kumar, Vikash.; Chatterjee, Amrita; Banerjee, Mainak.

    compound with maximum antifouling properties and hence was selected for further studies. The dose response studies were performed on compound 4j against 10 strains of Gram positive and Gram negative fouling bacteria with concentration ranging from 25...-fouling capacity of the compounds: Gram positive bacteria (Planococcus donghaensis) & Gram negative bacteria (Alcanivorax spp, Aeromonas hydrophila subsp hydrophila ATCC 7966, Aeromonas hydrophila subsp. salmonicida A449, Erythrobacter litoralis, Pseudomonas...

  13. The pathogenicity of different Botrytis cinerea Pers. isolates to apples and their sensitivity to benzimidazole fungicides

    Directory of Open Access Journals (Sweden)

    Hanna Bryk


    Full Text Available The pathogenicity of 80 isolates of Botrytis cinerea Pers. from different hosts to apple fruit was examined. Host specificity among isolates was not found. All of the isolates, independent of their derivation, caused apple fruit rot. Isolates from apple fruits showed moderate and strong pathogenicity to apple fruits. Only 1 of the 22 examined isolates showed weak pathogenicity. Tolerance to benomyl was compared among isolates obtained from apple fruits and from other hosts. It was found that 35% of isolates from apples showed resistance to benomyl. There was no correlation between the pathogenicity of isolates and their resistance to benomyl.

  14. The pathogenicity of different Botrytis cinerea Pers. isolates to apples and their sensitivity to benzimidazole fungicides


    Hanna Bryk


    The pathogenicity of 80 isolates of Botrytis cinerea Pers. from different hosts to apple fruit was examined. Host specificity among isolates was not found. All of the isolates, independent of their derivation, caused apple fruit rot. Isolates from apple fruits showed moderate and strong pathogenicity to apple fruits. Only 1 of the 22 examined isolates showed weak pathogenicity. Tolerance to benomyl was compared among isolates obtained from apple fruits and from other hosts. It was found that ...

  15. Tetrakis(1H-benzimidazole-κN3(nitrato-κOcopper(II nitrate

    Directory of Open Access Journals (Sweden)

    Fu-Lin Zhou


    Full Text Available In the title salt, [Cu(NO3(C7H6N24]NO3, one nitrate anion is coordinated to the CuII atom, which is also coordinated by the N atoms of four N-heterocycles. The geometry at the metal atom is a square pyramid in which the O atom of the anion occupies the apical position [Cu—O = 2.468 (5 and 2.590 (7 Å in the two independent formula units]. The cation lies on a twofold rotation axis; the coordinated nitrate anion is also disordered about this symmetry element. The lattice anion is also disordered about a twofold rotation axis. In the crystal, the cations are linked to the coordinated and free anions by N—H...O hydrogen bonds.

  16. 2-(2-Hydroxy-3-methoxyphenyl-1H-benzimidazol-3-ium perchlorate

    Directory of Open Access Journals (Sweden)

    Chuan Chen


    Full Text Available In the title molecular salt, C14H13N2O2+·ClO4−, the ring systems in the cation are almost coplanar [dihedral angle = 5.53 (13°]. Intramolecular N—H...O and O—H...O hydrogen bonds generate S(6 and S(5 rings, respectively. In the crystal, the two H atoms involved in the intramolecular hydrogen bonds also participate in intermolecular links to acceptor O atoms of the perchlorate anions. A simple intermolecular N—H...O bond also occurs. Together, these form a double-chain structure along [101].

  17. 1-Decyl-6-nitro-1H-benzimidazol-2(3H-one

    Directory of Open Access Journals (Sweden)

    Younes Ouzidan


    Full Text Available The title molecule, C17H25N3O3, is built up from fused six- and five-membered rings linked to a –C10H21 chain. The fused-ring system is essentially planar, the largest deviation from the mean plane being 0.009 (2 Å. The chain is roughly perpendicular to this plane, making a dihedral angle of 79.5 (2°. In the crystal, N—H...O hydrogen bonds build infinite chains along [010]. There are channels in the structure containing disordered hexane. The contribution of this solvent to the scattering power was suppressed using the SQUEEZE option in PLATON [Spek (2009. Acta Cryst. D65, 148–155].

  18. Biodegradation kinetics of the benzimidazole fungicide thiophanate-methyl by bacteria isolated from loamy sand soil. (United States)

    Cycoń, Mariusz; Wójcik, Marcin; Piotrowska-Seget, Zofia


    Degradation of the fungicide thiophanate-methyl (TM) by Enterobacter sp. TDS-1 and Bacillus sp. TDS-2 isolated from sandy soil previously treated with TM was studied in mineral salt medium (MSM) and soil. Both strains were able to grow in MSM supplemented with TM (50 mg l(-1)) as the sole carbon source. Over a 16 days incubation period, 60 and 77% of the initial dose of TM were degraded by strains TDS-1 and TDS-2, respectively, and disappearance of TM was described by first-order kinetics. Medium supplementation with glucose markedly stimulated bacterial growth; while the final rate of TM degradation was reduced by 21 and 27% for strains TDS-1 and TDS-2, respectively as compared to medium with TM only. Moreover, this additional carbon source changed the TM degradation kinetics, which proceeded according to a zero-order model. This effect was linked to substrate competition and/or a strong decrease of medium pH. Isolates degraded TM (100 mg kg(-1)) in soil with rate constants of 0.186 and 0.210 day(-1), following first-order rate kinetics, and the time in which the initial TM concentration was reduced by 50% (DT50) in soils inoculated with strains TDS-1 and TDS-2 were 6.3 and 5.1 days, respectively. Analysis of TM degradation products in soil showed that the tested strains may have the potential to transform carbendazim (MBC) to 2-aminobenzimidazole (2-AB), and may be useful for a bioremediation of MBC-polluted soils.

  19. Gold(I) Complexes of N-Heterocyclic Carbene Ligands Containing Benzimidazole: Synthesis and Antimicrobial Activity


    İlknur Özdemir; Nazan Temelli; Selami Günal; Serpil Demir


    Gold(I) N-heterocyclic carbene (NHC) complexes were obtained in good yields from the corresponding silver complexes by treatment with [AuCl(PPh3)] following the commonly used silver carbene transfer route. The silver complexes were synthesized from the benzimidazolium halide salts by the in situ reactions with Ag2O in dichloromethane as a solvent at room temperature. All gold complexes have been characterized by 1H-NMR, 13C-NMR and IR spectroscopy and elemental analysis. Au-NHC complexes were...

  20. Gold(I Complexes of N-Heterocyclic Carbene Ligands Containing Benzimidazole: Synthesis and Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    İlknur Özdemir


    Full Text Available Gold(I N-heterocyclic carbene (NHC complexes were obtained in good yields from the corresponding silver complexes by treatment with [AuCl(PPh3] following the commonly used silver carbene transfer route. The silver complexes were synthesized from the benzimidazolium halide salts by the in situ reactions with Ag2O in dichloromethane as a solvent at room temperature. All gold complexes have been characterized by 1H-NMR, 13C-NMR and IR spectroscopy and elemental analysis. Au-NHC complexes were evaluated for their in vitro antimicrobial activity against a variety of Gram-positive and Gram-negative bacteria and fungal species.

  1. Hydrogen bonding controlled catalysis of a porous organic framework containing benzimidazole moieties

    KAUST Repository

    Liu, Bing


    A microporous organic framework (JUC-Z12) was synthesized quantitatively from tetra(4-formylphenyl)methane and 3,3′-diaminobenzidine. JUC-Z12 shows high thermal stability (>400 °C), a large surface area (SBET = 750 m2 g-1), a well-defined uniform micropore distribution (1.09 nm) and high Qst for H2 (-8.1 kJ mol-1), CO2 (-29.5 kJ mol-1), and CH 4 (-22.2 kJ mol-1). It also exhibits selective catalytic activities in the Knoevenagel reaction, which is supposed to be controlled by hydrogen bonding between substrates and JUC-Z12. The JUC-Z12 catalyst can be easily isolated from the reaction mixture by simple filtration and reused with high activity. This journal is © the Partner Organisations 2014.

  2. Synthesis of sulfur and selenium heterocycles, including derivatives of imidazopyridine and benzimidazole


    Björk, Malin


    The chemistry developed in this thesis can be divided into two parts. The first part, which is the major part of the thesis, contains syntheses towards analogues to mutagenic heterocyclic amines found in e.g. meat fried at high temperatures. The second part concentrates on the palladium-(0)catalyzed cross-coupling reactions of 4- and 5-substituted 2,1,3-benzoselenadiazoles. The heterocyclic amines described can be divided into the linear and the angular compounds. Five l...

  3. Vibrational spectroscopic analysis, molecular dynamics simulations and molecular docking study of 5-nitro-2-phenoxymethyl benzimidazole (United States)

    Menon, Vidya V.; Foto, Egemen; Mary, Y. Sheena; Karatas, Esin; Panicker, C. Yohannan; Yalcin, Gözde; Armaković, Stevan; Armaković, Sanja J.; Van Alsenoy, C.; Yildiz, Ilkay


    FT-IR and FT-Raman spectra of 5-nitro-2-phenoxymethylbenzimidazole were recorded and analyzed theoretically and experimentally. The splitting of Nsbnd H stretching mode in the IR spectrum with a red shift from the calculated value indicates the weakening of the NH bond. The theoretical calculations give the phenyl ring breathing modes at 999 cm-1 for mono substituted benzene ring and at 1040 cm-1 for tri-substituted benzene ring. The theoretical NMR chemical shifts are in agreement with the experimental chemical shifts. The most reactive sites for electrophilic and nucleophilic attack are predicted from the MEP analysis. HOMO of π nature is delocalized over the entire molecule whereas the LUMO is located over the complete molecule except mono-substituted phenyl ring and oxygen atom. Reactive sites of the title molecule have been located with the help of ALIE surfaces and Fukui functions. In order to determine locations prone to autoxidation and locations interesting for starting of degradation, bond dissociation energies have been calculated for all single acyclic bonds. For the determination of atoms with pronounced interactions with water we have calculated radial distribution functions obtained after molecular dynamics simulations. The calculated first hyperpolarizability of the title compound is 58.03 times that of standard nonlinear optical material urea. The substrate binding site interactions of the title compound with Topo II enzyme is reported by using molecular docking study. Biological activity studies show that the title compound can be leaded for developing new anticancer agents.

  4. Bis-benzimidazole hits against Naegleria fowleri discovered with new high-throughput screens. (United States)

    Rice, Christopher A; Colon, Beatrice L; Alp, Mehmet; Göker, Hakan; Boykin, David W; Kyle, Dennis E


    Naegleria fowleri is a pathogenic free-living amoeba (FLA) that causes an acute fatal disease known as primary amoebic meningoencephalitis (PAM). The major problem for infections with any pathogenic FLA is a lack of effective therapeutics, since PAM has a case mortality rate approaching 99%. Clearly, new drugs that are potent and have rapid onset of action are needed to enhance the treatment regimens for PAM. Diamidines have demonstrated potency against multiple pathogens, including FLA, and are known to cross the blood-brain barrier to cure other protozoan diseases of the central nervous system. Therefore, amidino derivatives serve as an important chemotype for discovery of new drugs. In this study, we validated two new in vitro assays suitable for medium- or high-throughput drug discovery and used these for N. fowleri. We next screened over 150 amidino derivatives of multiple structural classes and identified two hit series with nM potency that are suitable for further lead optimization as new drugs for this neglected disease. These include both mono- and diamidino derivatives, with the most potent compound (DB173) having a 50% inhibitory concentration (IC50) of 177 nM. Similarly, we identified 10 additional analogues with IC50s of 500 times more potent than pentamidine. In summary, the mono- and diamidino derivatives offer potential for lead optimization to develop new drugs to treat central nervous system infections with N. fowleri.

  5. Microwave-assisted Syntheses and Crystal Structures of Benzimidazole Thiazolinone Derivatives

    Institute of Scientific and Technical Information of China (English)

    HU Jun; WANG Peng; WANG Ji-Kui; XU Yan-Hua


    A rapid and efficient microwave-assisted synthesis method for the preparation of 3-(lH-benzo[d]imidazol-2-yl)-2-substituted phenyl thiazolidin-4-one (4a, 4b) was described. The structures of 4a and 4b were determined by elemental analyses, IR, 1H NMR and X-ray diffraction. In the crystals of compounds 4a and 4b, the imidazole ring and two benzene rings are planar. Interestingly, the dihedral angle between two benzene rings is 71.5° in 4a, while it is almost perpendicular in 4b due to the different benzene substituents. Meanwhile, the thiazolidinone ring is planar in 4a while slightly distorted with an r.m.s deviation of 0.1494(2) A in 4b. The hydrogen bonding interactions observed link the molecules to form a dimeric unit, which may be effective in the stabilization of the structure.

  6. Highly Potent, Water Soluble Benzimidazole Antagonist for Activated (alpha)4(beta)1 Integrin

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, R D; Andrei, M; Lau, E Y; Lightstone, F C; Liu, R; Lam, K S; Kurth, M J


    The cell surface receptor {alpha}{sub 4}{beta}{sub 1} integrin, activated constitutively in lymphoma, can be targeted with the bisaryl urea peptidomimetic antagonist 1 (LLP2A). However, concerns on its preliminary pharmacokinetic (PK) profile provided an impetus to change the pharmacophore from a bisaryl urea to a 2-arylaminobenzimidazole moiety resulting in improved solubility while maintaining picomolar potency [5 (KLCA4); IC{sub 50} = 305 pM]. With exceptional solubility, this finding has potential for improving PK to help diagnose and treat lymphomas.

  7. 2,2′-(Ethane-1,2-diylbis(1H-benzimidazole

    Directory of Open Access Journals (Sweden)

    Guo-Liang Zhao


    Full Text Available The complete molecule of the title compound, C16H14N4, is generated by crystallographic inversion symmetry. In the crystal, molecules are linked by N—H...N hydrogen bonds, generating (001 sheets. Weak aromatic π–π stacking interactions [centroid–centroid distances = 3.7383 (13 and 3.7935 (14 Å] are also observed.

  8. Bis[μ-3-(1H-benzimidazol-2-ylbenzoato]dicopper(I

    Directory of Open Access Journals (Sweden)

    Zheng-Yu Su


    Full Text Available The dimeric title complex, [Cu2(C14H9N2O22], resides on a center of symmetry. In the crystal, the molecules are packed via π–π stacking interactions alternating between imidazole and benzene rings [mean interplanar distances = 3.754 (3 and 3.624 (3 Å]. An intermolecular N—H...O hydrogen bond links the dimers together. The two-coordinate CuI atom displays an O—Cu—N bond angle of 176.3 (2°. The Cu...Cu distance within the dimer is 5.100 (2 Å.

  9. Use of P-glycoprotein gene probes to investigate anthelmintic resistance in Haemonchus contortus and comparison with Onchocerca volvulus

    NARCIS (Netherlands)

    Kwa, M.S.G.; Okoli, M.N.; Schulz-Key, H.; Okongkwo, P.O.; Roos, M.H.


    A P-glycoprotein gene probe from the sheep parasitic nematode Haemonchus contortus was developed and used to analyse restriction fragment length polymorphisms between susceptible isolates and isolates resistant to either benzimidazole; levamisole and benzimidazole; or benzimidazole, ivermectin and c

  10. 5-Chloro-1-[(E-3-(dimethylaminoacryloyl]-3-methyl-1H-benzimidazol-2(3H-one–6-chloro-1-[(E-3-(dimethylaminoacryloyl]-3-methyl-1H-benzimidazol-2(3H-one (4/1

    Directory of Open Access Journals (Sweden)

    Rachida Dardouri


    Full Text Available In the reaction of 7-chloro-1,5-benzodiazepine-2,4-dione with N,N-dimethylformamide/dimethylacetal, the diazepine seven-membered ring undergoes a contraction to form the five-membered ring. The reaction yields two isomers the title compound, C13H14ClN3O2; the major component has the chlorine-atom substituent in the 5-position of the benzimidazolone ring and the minor component has the chlorine atom in the 6-position. The two isomers form a disordered co-crystal, the chloromethylbenzimidazolone portion of both components are disordered with respect to each other in a 4:1 ratio [the refined ratio is 0.816 (5:0.184 (5]; the dimethylaminocryloyl substitutent is ordered. The double bond of the dimethylaminoacryloyl substituent has an E configuration.

  11. A novel promising biomolecule immobilization matrix: synthesis of functional benzimidazole containing conducting polymer and its biosensor applications. (United States)

    Uzun, Sema Demirci; Unlu, Naime Akbasoglu; Sendur, Merve; Kanik, Fulya Ekiz; Timur, Suna; Toppare, Levent


    In order to construct a robust covalent binding between biomolecule and immobilization platform in biosensor preparation, a novel functional monomer 4-(4,7-di(thiophen-2-yl)-1H-benzo[d]imidazol-2-yl)benzaldehyde (BIBA) was designed and successfully synthesized. After electropolymerization of this monomer, electrochemical and spectroelectrochemical properties were investigated in detail. To fabricate the desired biosensor, glucose oxidase (GOx) was immobilized as a model enzyme on the polymer coated graphite electrode with the help of glutaraldehyde (GA). During the immobilization step, an imine bond was formed between the free amino groups of enzyme and aldehyde group of polymer. The surface characterization and morphology were investigated to confirm bioconjugation by X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM) at each step of biosensor fabrication. The optimized biosensor shows good linearity between 0.02mM and 1.20mM and a low limit of detection (LOD) of 2.29μM. Kinetic parameters Km(app) and Imax were determined as 0.94mM and 10.91μA, respectively. The biosensor was tested for human blood serum samples.

  12. Synthesis, antibacterial, antifungal activity and interaction of CT-DNA with a new benzimidazole derived Cu(II) complex. (United States)

    Arjmand, Farukh; Mohani, Bhawana; Ahmad, Shamim


    The ligand [C(16)H(10)O(2)N(4)S(2)] L has been synthesized by the condensation reaction of 2-mercaptobenzimidazole and diethyloxalate. The ligand L was allowed to react with bis(ethylenediamine)Cu(II)/Ni(II) complexes to yield [C(20)H(22)N(8)S(2)Cu]Cl(2)1 and [C(20)H(22)N(8)S(2)Ni]Cl(2)2 complexes. The Ni(II) complex was synthesized only to elucidate the structure of the complex. The complexes 1 and 2 were characterized by elemental analyses, IR, NMR, EPR, UV-vis spectroscopy and molar conductance measurements. Both the complexes are ionic in nature and possess square-planar geometry. The binding of the complex 1 to calf thymus DNA was investigated spectrophotometrically. The absorption spectra of complex 1 exhibits a slight red shift with "hyperchromic effect" in presence of CTDNA. Electrochemical analysis and viscosity measurements were also carried out to ascertain the mode of binding. The complex 1 in the absence and in presence of CT DNA in aqueous solution exhibits one quasi-reversible redox wave corresponding to Cu(II)/Cu(I) redox couple at a scan rate of 0.2 V s(-1). The shift in DeltaE(p), E(1/2) and I(pa)/I(pc) values ascertain the interaction of calf thymus DNA with copper(II) complex. There is decrease in viscosity of CTDNA which indicates that the complex 1 binds to CTDNA through a partial intercalative mode. The antibacterial and antifungal studies of the [C(7)H(6)N(2)S], [C(4)H(16)N(4)Cu]Cl(2,) [C(16)H(10)N(4)S(2)O(2)] and [C(20)H(22)N(8)S(2)Cu]Cl(2) were carried out against S. aureus, E. coli and A. niger. All the results reveal that the complex 1 is highly active against the bacterial strains and also inhibits fungal growth.

  13. Optimization of a novel class of benzimidazole-based farnesoid X receptor (FXR) agonists to improve physicochemical and ADME properties. (United States)

    Richter, Hans G F; Benson, G M; Bleicher, K H; Blum, D; Chaput, E; Clemann, N; Feng, S; Gardes, C; Grether, U; Hartman, P; Kuhn, B; Martin, R E; Plancher, J-M; Rudolph, M G; Schuler, F; Taylor, S


    Structure-guided lead optimization of recently described benzimidazolyl acetamides addressed the key liabilities of the previous lead compound 1. These efforts culminated in the discovery of 4-{(S)-2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetylamino}-3-fluoro-benzoic acid 7g, a highly potent and selective FXR agonist with excellent physicochemical and ADME properties and potent lipid lowering activity after oral administration to LDL receptor deficient mice.

  14. Inhibition of partially purified K+/H+-ATPase from guinea-pig isolated and enriched parietal cells by substituted benzimidazoles.


    Beil, W.; Sewing, K F


    The cellular and subcellular distributions of adenosinetriphosphatases (ATPases) were examined in guinea-pig gastric mucosal cells. All cell types displayed Mg2+-ATPase and bicarbonate (HCO3-)-stimulated ATPase activity. K+-ATPase was located only in fractions derived from parietal cells. Differential and density-gradient centrifugation of material prepared from parietal cells revealed that K+-ATPase activity was located in a tubulo-vesicular membrane fraction. Enzyme activity was ten fold gr...

  15. Synthesis and properties of poly(aryl sulfone benzimidazole) and its copolymers for high temperature membrane electrolytes for fuel cells

    DEFF Research Database (Denmark)

    Yang, Jingshuai; Li, Qingfeng; Cleemann, Lars Nilausen


    , the membrane swelling was reduced and the mechanical strength was improved, as compared with their meta structured analogues. At an acid doping level of 11 mol H3PO4 per average molar repeat unit, the Co-20%SO2PBI membrane exhibited a tensile strength of 16 MPa at room temperature and an H2-air fuel cell peak...

  16. Use of benzimidazole agar plates to assess fall armyworm (Lepidoptera: Noctuidae) feeding on excised maize and sorghum leaves (United States)

    The fall armyworm, Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) is an economically significant pest of sorghum and maize. To screen sorghum and maize germplasm for resistance to fall armyworm feeding, field, greenhouse, or lab bioassays are often utilized individually or in combinatio...

  17. Benzimidazole derivative small-molecule 991 enhances AMPK activity and glucose uptake induced by AICAR or contraction in skeletal muscle

    DEFF Research Database (Denmark)

    Bultot, Laurent; Jensen, Thomas Elbenhardt; Lai, Yu-Chiang


    be beneficial for both purposes. Here, we investigated if a recently described potent AMPK activator called 991, in combination with the commonly used activator 5-aminoimidazole-4-carboxamide riboside or contraction, further enhances AMPK activity and glucose transport in mouse skeletal muscle ex vivo. Given...... that the γ3-subunit is exclusively expressed in skeletal muscle and has been implicated in contraction-induced glucose transport, we measured the activity of AMPKγ3 as well as ubiquitously expressed γ1-containing complexes. We initially validated the specificity of the antibodies for the assessment...... profoundly enhanced AMPKγ1/γ3 complex activation and glucose transport compared with any of the single treatments. The study demonstrates the utility of a dual activator approach to achieve a greater activation of AMPK and downstream physiological responses in various cell types, including skeletal muscle....

  18. Synthesis, X-ray structure and theoretical investigation of 2-(2'-quinolyl)benzimidazole metal complexes

    Indian Academy of Sciences (India)



    Synthesis, characterization and DFT analysis of 2-(1H-benzo[d]imidazol-2-yl)quinoline (BQ) and its cobalt and manganese coordination compounds {Co(DMF)(BQ) Cl₂} and {Mn(DMF)(BQ) Cl₂} have been described. The ligand, 2-(1H-benzo[d]imidazol-2-yl)quinoline (BQ) crystallizes in non-centrosymmetric monoclinic crystal system with cell parameters a = 12.9280(4) Å, b = 7.9429(3) Å, c = 25.8478(9) Å, α =γ = 90◦, β = 103.005(2)◦. {Co(DMF)(BQ)Cl₂} and {Mn(DMF)(BQ)Cl₂} crystallized in triclinic space group P-1. The metal(II) environment exhibits trigonal bipyramidal coordination. These complexes show presence of N–H. . .Cl, C–H...Cl hydrogen bonds and strong intramolecular C–H...O interactions. The structure parameters were calculated and they are in good agreement with those observed experimentally. Theoretically calculated frontier molecular orbitals (HOMO–LUMO) of the complexes and their energies indicate intermolecular chargetransfer and delocalization of electron density within the molecule.

  19. Inhibition of Mild Steel Corrosion in 1M H2SO4 Medium by Benzimidazole Mannich bases

    Directory of Open Access Journals (Sweden)

    P. M. Dasami


    Full Text Available The corrosion inhibition behaviour of two synthesized Mannich bases has been investigated for mild steel in 1M H2SO4 by weight loss and electrochemical techniques.The inhibition efficiency depends on concentration of the inhibitor and temperature. The inhibitors function by adsorption on mild steel surface and obey Langmuir isotherm indicating monolayer adsorption on the surface. Thermodynamic parameters show that the adsorption of the inhibitors occurs through electrostatic interaction. Polarization studies reveal that the inhibitors behave as mixed type in 1M H2SO4 affecting both anodic metal dissolution and cathodic hydrogen evolution. SEM studies show the formation of surface adsorptive film of the Mannich bases on the mild steel surface.

  20. Crystal structure of 3-(2-hydroxyethyl-2-methylsulfanyl-6-nitro-3H-benzimidazol-1-ium chloride monohydrate

    Directory of Open Access Journals (Sweden)

    Akoun Abou


    Full Text Available In the cation of the title hydrated molecular salt, C10H12N3O3S+·Cl−·H2O, the benzimidazolium ring system is almost planar (r.m.s. deviation = 0.006 Å and the nitro group is inclined at an angle of 4.86 (9° to this plane. In the crystal, C—H...O hydrogen bonds form centrosymmetric R22(20 dimers and these are further aggregated through N—H...O and O—H...Cl hydrogen bonds involving the water molecules and chloride anions. Aromatic π–π stacking interactions are also found between two parallel benzene rings or the benzene and imidazolium rings, with centroid–centroid distances of 3.5246 (9 and 3.7756 (9 Å, respectively. Analysis of the bond lengths and comparison with related compounds show that the nitro substituent is not involved in conjugation with the adjacent π-system and hence has no effect on the charge distribution of the heterocyclic ring.

  1. Bis[bis-(1-ethyl-benzimidazol-2-ylmeth-yl) ether]cobalt(II) dipicrate dimethyl-formamide disolvate. (United States)

    Wu, Huilu; Yun, Ruirui; Sun, Tao; Li, Ke; Meng, Xuan


    In the title complex, [Co(C(20)H(22)N(4)O)(2)](C(6)H(2)N(3)O(7))(2)·2C(3)H(7)NO, the Co(II) ion is coordinated by two sets of two N atoms and an O atom from two independent tridendate ligands in a distorted octa-hedral coordination environment. There are significant differences between chemically equivalent coordination bond lengths. The crystal structure is stabilized by weak inter-molecular C-H⋯O hydrogen bonds and weak π-π stacking inter-actions [centroid-centroid distance 3.495 (1) Å]. In one of the anions one nitro group is rotationally disordered about the C-N bond with refined occupancies of 0.524 (8) and 0.476 (8).

  2. A fluorescence switch based on a controllable photochromic naphthopyran group

    Energy Technology Data Exchange (ETDEWEB)

    Chen Lizhen [Faculty of Chemistry, Northeast Normal University, Changchun 130024 (China); Wang Guang, E-mail: [Faculty of Chemistry, Northeast Normal University, Changchun 130024 (China); Zhao Xiancai [Faculty of Chemistry, Northeast Normal University, Changchun 130024 (China)


    A fluorescence switch based on photoisomerization of naphthopyran (NP) has been designed by employing 2-(pyridin-2-yl)-benzimidazole (BPI) and the naphthopyran containing two pyran rings (NP) as fluorescent dye and photochromic compound, respectively. The fluorescence switch of benzimidazole derivative can be modulated either by controlling the irradiation time of UV light or by adjusting the amount ratio of fluorescent benzimidazole derivative to photochromic naphthopyran in both solution and polymethyl methacrylate (PMMA) film. The experimental results indicated that the decrease of fluorescence intensity of benzimidazole derivative is attributed to the interaction of benzimidazole with naphthopyran. - Highlights: > Naphthopyran was first used to fabricate fluorescence switch with benzimidazole derivative. > Fluorescence intensity can be modulated by controlling the UV irradiation time. > Fluorescence intensity can be adjusted by changing the ratio of benzimidazole derivative to naphthopyran. > Decrease of fluorescence intensity is attributed to the interaction of benzimidazole derivative and naphthopyran.

  3. Benzimidazole -Resistance in Haemonchus Contortus: New PCR-RFLP Method for the Detection of Point Mutation at Codon 167 of Isotype 1 Β-Tubulin Gene

    Directory of Open Access Journals (Sweden)

    A Eslami


    Full Text Available Background: Due to the lack of a suitable and economic test for the analysis of the polymorphism at codon 167, we developed a new PCR-RFLP technique, based on a modified forward primer (UT-HC167 MF-primer, to identify simultaneously the SNPs at codons 167 and 200 of isotype 1 β-tubu­lin gene of Haemonchus contortus.Methods: There already are several safe and easy methods for identification of point mutations at codons 198 and 200. Due to the lack of a reliable and easy method for the detection of the single nucleo­tide polymorphism (SNP at codon 167, we developed an innovative PCR-RFLP technique based on a modified forward primer (UT-HC167 MF-primer, in which the nucleotide T at the posi­tion 443 was substituted through a nucleotide A creating a restriction site for restriction endonuc­lease SnaB I in the nucleotide sequences including codon 167. A total of 138 adult male H. contortus were collected from three different geo-climatic areas of Iran. The isolated genomic DNA of each single worm was amplified by PCR using primers flanking codon 167. The PCR product (527 bp was then amplified by semi-nested PCR using the UT-HC167 MF-primer and the reverse primer achiev­ing a PCR product of 451 bp in length. This PCR product was subsequently digested with the restriction endonucleases SnaB I and TaaI for analysis of the mutations at codons 167 and 200, respec­tively.Results: All worms had two alleles encoding for phenylalanine (BZss homozygote for both codons.Conclusion: Using the UT-HC167 MF-primer and a suitable reverse primer designed upstream from codon 200, it is possible to amplify a PCR product which can be used for analysis of the SNPs at all three mentioned codons using RFLP.

  4. Imidazole- and Benzimidazole-Based Inhibitors of the Kinase IspE : Targeting the Substrate-Binding Site and the Triphosphate-Binding Loop of the ATP Site

    NARCIS (Netherlands)

    Mombelli, Paolo; Le Chapelain, Camille; Munzinger, Noah; Joliat, Evelyne; Illarionov, Boris; Schweizer, W. Bernd; Hirsch, Anna K. H.; Fischer, Markus; Bacher, Adelbert; Diederich, Francois


    The enzymes of the mevalonate-independent biosynthetic pathway to isoprenoids are attractive targets for the development of new drug candidates, in particular against malaria and tuberculosis, because they are present in major human pathogens but not in humans. Herein, the structure-based design, sy

  5. Cytotoxic activity, X-ray crystal structures and spectroscopic characterization of cobalt(II), copper(II) and zinc(II) coordination compounds with 2-substituted benzimidazoles. (United States)

    Sánchez-Guadarrama, Obdulia; López-Sandoval, Horacio; Sánchez-Bartéz, Francisco; Gracia-Mora, Isabel; Höpfl, Herbert; Barba-Behrens, Noráh


    Herein we present the synthesis, structural and spectroscopic characterization of coordination compounds of cobalt(II), copper(II) and zinc(II) with 2-methylbenzimidazole (2mbz), 2-phenylbenzimidazole (2phbz), 2-chlorobenzimidazole (2cbz), 2-benzimidazolecarbamate (2cmbz) and 2-guanidinobenzimidazole (2gbz). Their cytotoxic activity was evaluated using human cancer cell lines, PC3 (prostate), MCF-7 (breast), HCT-15 (colon), HeLa (cervic-uterine), SKLU-1 (lung) and U373 (glioblastoma), showing that the zinc(II) and copper(II) compounds [Zn(2mbz)(2)Cl(2)].0.5H(2)O, [Zn(2cmbz)(2)Cl(2)].EtOH, [Cu(2cmbz)Br(2)].0.7H(2)O and [Cu(2gbz)Br(2)] had significant cytotoxic activity. The isostructural cobalt(II) complexes showed not significant activity. The cytotoxic activity is related to the presence of halides in the coordination sphere of the metal ion. Recuperation experiments with HeLa cells, showed that the cells recuperated after removing the copper(II) compounds and, on the contrary, the cells treated with the zinc(II) compounds did not. These results indicate that the mode of action of the coordination compounds is different.

  6. Resistance of Colletotrichum gloeosporioides to Benzimidazole Fungicide Carbendazim in Camellia oleifera Nurseries%油茶苗圃炭疽病菌抗药性研究

    Institute of Scientific and Technical Information of China (English)

    李河; 周国英; 章怀云; 刘君昂; 彭宽


    The fungicide resistance of anthracnose in Camellia oleifera nurseries was investigated in Liuyang,Changning,and other regions in Hunan Province.The Colletotrichum gloeosporioides strains from the former two regions were highly resistant to carbendazim.After subcultured for 10 generations on fungicide-free medium,the resistant strains grew well on the medium containing carbendazim 450 μg/mL and suggesting that its resistance was stable.The β-tubulin genes from the resistant and susceptible strains were cloned and sequenced.The coding region was 1 344 bp nucleotides and predicted to encode a protein with 447 amino acids.Comparison of the β-tubulin amino acid sequences between resistant and susceptible strains of Colletotrichum gloeosporioides revealed that a mutation leading to an amino acid substitution at the position 198 from glutamic acid in the susceptible strain to alanine in the resistant strain.Finally,the main morphological characteristics of C.gloeosporioides were descripted,but it could not be used to determine the resistance to carbendazim.

  7. Poly[chlorido[μ4-2,2′-(2-methyl-1H-benzimidazol-3-ium-1,3-diyldiacetato]zinc

    Directory of Open Access Journals (Sweden)

    Jia-Qin Liu


    Full Text Available The title compound, [Zn(C12H11N2O4Cl]n, contains a centrosymmetric dimetal tetracarboxylate paddle-wheel moiety in which the ZnII atom is square-pyramidally coordinated by four carboxylate O atoms at the basal positions and one Cl− anion at the apical position. Each paddle-wheel unit is joined to four such neighbours through bridging dicarboxylate ligands, producing a two-dimensional undulating layer parallel to (-101. Adjacent sheets are stacked in a parallel fashion to form a three-dimensional supramolecular structure which is stabilized by interlayer π–π interactions between benzene rings, with a centroid–centroid distance of 3.722 Å. The range of Zn—O bond lengths is 2.0440 (17–2.1256 (15 Å and the Zn—Cl bond length is 2.2622 (6 Å.

  8. Solid phase extraction-preconcentration and high performance liquid chromatographic determination of 2-mercapto-(benzothiazole, benzoxazole and benzimidazole) using copper oxide nanoparticles. (United States)

    Parham, Hooshang; Khoshnam, Farzaneh


    This study introduces a novel method of solid phase extraction (SPE), preconcentration and HPLC determination of 2-mercaptobenzimidazole (2MBI), 2-mercaptobenzoxazole (2MBO) and 2-mercaptobenzothiazole (2MBT) from an aqueous solution by a SPE cartridge loaded with copper oxide nanoparticles. Results demonstrated that copper oxide nanoparticles are quite efficient for extraction and preconcentration of trace amounts of these mercaptans at room temperature. The study also investigated the effects of parameters such as pH, buffer and its volume, electrolyte concentration, flow rate of the test solution, composition and volume of the desorbing solvent, accepted tolerable volume, amount of adsorbent, reusability of cartridges and evidence of some co-existing species on extraction and determination of the above mentioned mercaptans. The method showed good linearity for determination of these mercaptans in the range of 0.01-10 μg mL(-1) with regression coefficients better than 0.9969. The limits of detection (LODs) evaluations were 0.0021, 0.0027 and 0.0019 μg mL(-1) for 2MBT, 2MBO and 2MBI, respectively. The relative standard deviations (RSDs) for 0.2 μg mL(-1) and 5 μg mL(-1) of the measured mercaptans were below 3.04% and 4.23%, respectively. Ramin Power Plant (3000 MW, Ahvaz, Iran) cooling water containing some 2MBT (as corrosion inhibitor) was used as the real sample. Recovery tests with spiked levels of 2MBT, 2MBI and 2MBO were carried out and satisfied results were obtained.

  9. [Research of imidazo[1,2-a]benzimidazole derivatives. XXX. Synthesis and properties of (imidazo[1,2-a]benzimidazolyl-2)acetic acid derivatives]. (United States)

    Anisimova, V A; Tolpygin, I E; Spasov, A A; Serdiuk, T S; Sukhov, A G


    Ethyl esters of (9-subtituted-imidazo[1,2-a]benzimidazolyl-2)acetic acids were synthesized. The chemical properties of these esters (hydrolysis, decarboxylation, hydrazinolysis) and biological activity (fungicidal, antimicrobial, antiarrhythmic activity, and also affects on the brain rhythmogenesis) of the prepared compounds were studied.

  10. Ethyl 2-(4-bromophenyl-1-[3-(1H-imidazol-1-ylpropyl]-1H-benzimidazole-5-carboxylate monohydrate

    Directory of Open Access Journals (Sweden)

    Yeong Keng Yoon


    Full Text Available In the title compound, C22H21BrN4O2·H2O, the two pyrazole rings are essentially planar [maximum deviations 0.002 (1 and 0.002 (1 Å], and form a dihedral angle of 73.46 (9°. The dihedral angle between the benzene rings is 29.33 (7°. In the crystal, molecules are connected via C—H...O and O—H...N hydrogen bonds, forming layers in the ab plane.

  11. Progress Toward a Scalable Synthesis of Azaspirene, An Angiogenesis Inhibitor and Synthesis of 2-Amino- benzimidazole Compounds Targeting Subdomain IIa of the Internal Ribosome Entry Site Inhibiting Translation of The Hepatitis C Virus


    Schmit, David John


    Chemical studies toward the synthesis of an angiogenesis inhibitor azaspirene is described. There is a need for a concise and scalable asymmetric synthesis of azaspirene. The current strategy employed can lead to the production of small libraries of azaspirene derivatives and other members of the pseurotin family, where structure activity relationship (SAR) studies can be conducted in anticipation of creating innovative and more effective anti-cancer drugs. Amino acids as well as other optica...

  12. Discovery of 3-(5'-Substituted)-Benzimidazole-5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors: Design, Synthesis, and Biological Evaluation. (United States)

    Yan, Wei; Wang, Xinyi; Dai, Yang; Zhao, Bin; Yang, Xinying; Fan, Jun; Gao, Yinglei; Meng, Fanwang; Wang, Yuming; Luo, Cheng; Ai, Jing; Geng, Meiyu; Duan, Wenhu


    Fibroblast growth factor receptor (FGFR) represents an attractive oncology target for cancer therapy in view of its critical role in promoting cancer formation and progression, as well as causing resistance to approved therapies. In this article, we describe the identification of the potent pan-FGFR inhibitor (R)-21c (FGFR1-4 IC50 values of 0.9, 2.0, 2.0, and 6.1 nM, respectively). Compound (R)-21c exhibited excellent in vitro inhibitory activity against a panel of FGFR-amplified cell lines. Western blot analysis demonstrated that (R)-21c suppressed FGF/FGFR and downstream signaling pathways at nanomolar concentrations. Moreover, (R)-21c provided nearly complete inhibition of tumor growth (96.9% TGI) in NCI-H1581 (FGFR1-amplified) xenograft mice model at the dose of 10 mg/kg/qd via oral administration.

  13. Synthesis and Crystal Structure of a Dinuclear Cu(Ⅱ) Complex [Cu(C13H9N2O)Cl]2·(CH3CN)2 with Ligand 2-Benzimidazol

    Institute of Scientific and Technical Information of China (English)

    LI Qing-Xiang; YANG Xiang-Liang; XU Hui-Bi


    A new dinuclear copper complex, [Cu(C13H9N2O)Cl]2·(CH3CN)2 (C30H24Cl2Cu2N6O2),has been synthesized and characterized by X-ray structure determination. It crystallizes in the triclinic system, space group P1-, with a = 7.6677(14), b = 9.2375(17), c = 11.227(2) (A), α = 81.338(3),β= 88.173(4), γ = 66.199(3)°, V = 718.9(2) (A)3, Z = 1, Mr = 698.53, F(000) = 354, Dc = 1.613 g/cm3,μ(MoKα) = 1.705 mm-1, the final R = 0.0645 and wR = 0.1364 for 2474 unique reflections with 1809 observed ones (I> 2σ(Ⅰ)). In the title complex, each copper(Ⅱ) atom is located at the center of a distorted tetrahedron consisting of four coordinate atoms (one nitrogen atom, two oxygen anions,and one chlorine atom). Two copper(Ⅱ) atoms are bridged by two oxygen anions (O(1) and O(1a)) of two phenolates to form a Cu(Ⅱ)-Cu(Ⅱ) binuclear entity, and the distance between two copper(Ⅱ)atoms is 3.0144(15) (A).

  14. Synthesis and Characterization of 2-Substituted-benzimidazole Copper(Ⅱ) Complexes under Microwave Irradiation%2-取代苯并咪唑铜(Ⅱ)配合物的微波合成与表征

    Institute of Scientific and Technical Information of China (English)

    邱琦; 黄旭珊; 吕维忠; 曹慧群; 王芳; 罗仲宽


    采用2-取代基苯并咪唑化合物、氯化铜为原料、丙酮或2-丁酮为溶剂,在微波辐射下合成了2-苄基苯并咪唑(BIm_a)和1-(对甲氧基苄基)-2-(对甲氧基苯基)苯并咪唑(BIm_b)的铜配合物,收率分别为80%和75%.测得BIm_a和BIm_b铜配合物熔点分别为144.7~145.8 ℃和224.5~226.0℃.应用摩尔电导率、XRD、紫外光谱、SEM和热分析测试对目标配合物进行表征,摩尔电导率、紫外和红外光谱解析表明,2-取代苯并咪唑配体与Cu(Ⅱ) 发生了配合反应;XRD和SEM表征证明晶型为单斜晶系;热分析得出BIm_a、BIm_b和氯化铜的配位数分别为1和1/2.

  15. A thermo-responsive supramolecular organogel: dual luminescence properties and luminescence conversion induced by Cd(2+). (United States)

    Ma, Xinxian; Zhang, Jinjin; Tang, Ning; Wu, Jincai


    A simple dual luminescent acylhydrazone-functionalized benzimidazole derivative (L) was blended with ethylene glycol affording a thermo-responsive green-light-emitting supramolecular gel (G-gel). This G-gel can convert to a blue-light-emitting gel (B-gel) by strongly increasing the luminescence of the benzimidazole moiety upon addition of one equivalent of Cd(2+).

  16. Synthesis of Some Phenylpyrazolo Benzimidazolo Quinoxaline Derivatives as Potent Antihistaminic Agents

    Directory of Open Access Journals (Sweden)

    C. H. Sridevi


    Full Text Available 2,3-Diphenyl quinoxaline (NI was fused with benzimidazole (NII by a methylene bridge, which was then allowed for acetylation. The acetylated product (NIV was made to react with different aromatic aldehydes to give chalcones (NV1-NV5. Chalcones refluxed with substituted acid hydrazides to afford different phenyl pyrazolo benzimidazole quinoxaline derivatives (NVI 1-NVI 15. The structure of chalcones and phenyl pyrazolo benzimidazole quinoxaline derivatives were confirmed by m.p, TLC and spectral data. All the synthesized compounds were screened for their antihistaminic activity. Compounds NVI-3, NVI-12, NVI-13, NVI-14 and NVI-15 were shown good % protection of antihistamic activity.

  17. Synthesis and pharmacological evaluation of several N-(2-nitrophenylpiperazine derivatives

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    Full Text Available Six newly synthesized heterocyclic (2-nitrophenylpiperazines, with a specific structure of the heteroaryl group, whichmimics the catechol moiety of dopamine (benzimidazoles and substituted benzimidazoles, were evaluated for their binding affinity to rat dopamine (DA, serotonin (5-HT and α1 receptors. All compounds with a benzimidazole group had a 5-HT2A/D2 receptors binding ratio characteristic for atypical neuroleptics (>1, pKi values. Compound 7c, 4-bromo-6-{2-[4-(2-nitrophenylpiperazin-1-yl]ethyl}-1H-benzimidazole, expressed higher affinities for all receptor classes than clozapine. Also, it exhibited the best characteristic for atypical neuroleptics and presents a compound with the best profile for further in vivo investigations.

  18. Reissert compound of bisbenzimidazole



    A Reissert compound of bisbenzimidazole can be formed by first reacting benzimidazole with an aliphatic diacid chloride to form bisbenzimidazole and then reacting the bisbenzimidazole with an aliphatic acid chloride and cyanide to form the Reissert compound thereof.

  19. Formation of Reissert compound of bisbenzimidazole



    A Reissert compound of bisbenzimidazole can be formed by first reacting benzimidazole with an aliphatic diacid chloride to form bisbenzimidazole and then reacting the bisbenzimidazole with an aliphatic acid chloride and cyanide to form the Reissert compound thereof.

  20. Progress report for subcontract 9-X33-LO152-1

    Energy Technology Data Exchange (ETDEWEB)

    Storm, C.B.; Butcher, R.J.


    X-ray structural studies were made for complexes of Co ions with ammonia, 4-nitroimidazole, benzimidazole, aniline, pyridine, DMSO, en, 4-nitropyrazole, histidine, 4-nitrohistidine, 4-chloroimidazole. Synthetic procedures are given. Molecular modeling is discussed.

  1. Antiparasitic mebendazole shows survival benefit in 2 preclinical models of glioblastoma multiforme


    Bai, Ren-Yuan; Staedtke, Verena; apRhys, Colette M.; Gallia, Gary L.; Riggins, Gregory J.


    Glioblastoma multiforme (GBM) is the most common and aggressive brain cancer, and despite treatment advances, patient prognosis remains poor. During routine animal studies, we serendipitously observed that fenbendazole, a benzimidazole antihelminthic used to treat pinworm infection, inhibited brain tumor engraftment. Subsequent in vitro and in vivo experiments with benzimidazoles identified mebendazole as the more promising drug for GBM therapy. In GBM cell lines, mebendazole displayed cytoto...

  2. [Zn(bim)2]·(H2O)1.67: A metal-organic open-framework with sodalite topology

    Institute of Scientific and Technical Information of China (English)

    HUANG Xiaochun; ZHANG Jiepeng; CHEN Xiaoming


    The new coordination polymer formulated as [Zn(bim)2]@(H2O)1.67 (Hbim = benzimidazole, bim = benzimidazolate) has been synthesized and shown by single-crystal structural analysis to be a three-dimensional network with the 4264 sodalite topology, constructed by tetrahedral building blocks, [Zn(bim)4]2-. Each sodalite cage defined by the 24 zinc atoms at the apexes centers hosts 10 water molecules (ca. 18% occupancy).

  3. catena-Poly[[bis[μ-2-(3-pyridyl-1H-benzimidazole]-κ2N2:N3;κ2N3:N2-disilver(I]-μ-2,5-dicarboxybenzene-1,4-dicarboxylato-κ2O2:O5

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    Jie Chen


    Full Text Available The title coordination polymer, [Ag2(C10H4O8(C12H9N32]n, was prepared by a hydrothermal method. The AgI atom exists in a strongly distorted trigonal coordination environment. Two AgI ions related by an inversion centre are coordinated by two 2-(3-pyridylbenzimidazole ligands, forming a centrosymmetric cyclic dimer. The bridging bidentate 2,5-dicarboxybenzene-1,4-dicarboxylate ligand is also located on an inversion centre and connects the binuclear units, generating a one-dimensional polymer. The almost-planar conformation of this ligand allows it to form a strong intramolecular O—H...O hydrogen bond. Finally, intermolecular N—H...O hydrogen bonds aggregate the chains into a three-dimensional framework.

  4. 反相高效液相色谱法同时测定动物组织中苯并咪唑类兽药残留量%Simultaneous Determination of Benzimidazole Residues in Animal Tissues by Reversed Phase High Performance Liquid Chromatography

    Institute of Scientific and Technical Information of China (English)

    陈毓芳; 彭肖颜



  5. Conformational Analysis of Poly-2,5-Benzimidazole (ABPBI), Poly-2,5- Benzoxazole (ABPBO), and Poly-2,6-Benzothiazole (ABPBT) Dimers by the Modified Neglect of Diatomic Overlap (MNDO) and Austin Method 1 (AM1) Semiempirical Molecular Orbital Methods (United States)


    AFWAL-TR-87-4034 A\\) CONFORMATIONAL ANALYSIS OF POLY-2,5-BENZOIMIDAZOLE (ABPBI), POLY-2,5-BENZOXAZOLE (ABPBO), AND POLY-2,6- BENZOTHIAZOLE (ABPBT... benzothiazole Molecular Orbital 19. ABSTRACT (Continue on reverse if necessar and identif-y by block number) The two repeat unit analogs of three, aromatic...SECURITY CLASSIFICATION OF THIS PAGE 11. TITLE (Cont) Poly-2,5-benzoxazole (ABPBO), and Poly-2,6- benzothiazole (ABPBT) Dimers by the Modified Neglect

  6. meso-4,4′-Dimethoxy-2,2′-{[(3aR,7aS-2,3,3a,4,5,6,7,7a-octahydro-1H-benzimidazole-1,3-diyl]bis(methylene}diphenol

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    Augusto Rivera


    Full Text Available The title compound, C23H30N2O4, a di-Mannich base derived from 4-methoxyphenol and cis-1,2-diaminecyclohexane, has a perhydrobenzimidazolidine nucleus, in which the cyclohexane ring adopts a chair conformation and the heterocyclic ring has a half-chair conformation with a C—N—C—C torsion angles of −48.14 (15 and −14.57 (16°. The mean plane of the heterocycle makes dihedral angles of 86.29 (6 and 78.92 (6° with the pendant benzene rings. The molecular structure of the title compound shows the presence of two interactions between the N atoms of the imidazolidine ring and the hydroxyl groups through intramolecular O—H...N hydrogen bonds with graph-set motif S(6. The unobserved lone pairs of the N atoms are presumed to be disposed in a syn conformation, being only the second example of an exception to the typical `rabbit-ears' effect in 1,2-diamines.

  7. 4,4′-Diiodo-2,2′-[(3aR,7aR-2,3,3a,4,5,6,7,7a-octahydro-1H-1,3-benzimidazole-1,3-diylbis(methylene]diphenol

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    Augusto Rivera


    Full Text Available In the crystal structure of the title compound, C21H24I2N2O2, the two N atoms of the imidazolidine moiety are linked to the hydroxy groups by intramolecular O—H...N hydrogen-bonding interactions. The cyclohexane ring adopts a chair conformation and the heterocyclic ring to which it is fused has a twisted envelope conformation.

  8. Dimethyl 4,4′-dihydroxy-3,3′-{[(3aRS,7aRS-2,3,3a,4,5,6,7,7a-octahydro-1H-1,3-benzimidazole-1,3-diyl]bis(methylene}dibenzoate

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    Augusto Rivera


    Full Text Available The title compound, C25H30N2O6, has the imidazolidine ring in an envelope conformation. There are two intramolecular O—H...N hydrogen-bond interactions with graph-set motif S(6. The cyclohexane ring adopts a slightly distorted chair conformation. One methyl carboxylate substituent forms a dihedral angle of 12.00 (5° with the plane of the benzene ring, while the other methyl carboxylate group is almost coplanar, making a dihedral angle of 2.26 (9°. In the crystal, pairs of intermolecular C—H...O hydrogen bonds form racemic dimers, corresponding to an R22(18 graph-set motif. Further weak C—H...O interactions generate a chain running along the c axis.

  9. Di-n-propyl 4,4′-dihydroxy-3,3′-{[(3aRS,7aRS-2,3,3a,4,5,6,7,7a-octahydro-1H-benzimidazole-1,3-diyl]bis(methylene}dibenzoate

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    Karla Fejfarová


    Full Text Available The title compound, C29H38N2O6, was prepared as model for studying intramolecular hydrogen-bonding interactions. Molecules of the title compound are located on a crystallographic twofold rotation axis, which passes through the C atom linked to the two N atoms on the imidazolidine ring. The molecular structure shows the existence of two intramolecular O—H...N hydrogen-bonding interactions between the two N atoms of the imidazolidine moiety and the hydroxy groups in the aromatic rings. The crystal structure shows the strain of ring fusion in the perhydrobenzimidazole moiety according to the endocyclic bond angles and the torsion angles, which evidence a puckering of the cyclohexane ring with respect to normal tetrahedral bond angles in an ideal chair conformation.

  10. 4,4′-Dimethoxy-2,2′-{[(3aRS,7aRS-2,3,3a,4,5,6,7,7a-octahydro-1H-1,3-benzimidazole-1,3-diyl]bis(methylene}diphenol

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    Augusto Rivera


    Full Text Available The title compound, C23H30N2O4, is a Mannich base useful for studying the effect of an electron-donating phenol substituent on intramolecular hydrogen bonding. In the molecular structure, the cyclohexane ring adopts a chair conformation and the five-membered ring has a twisted envelope conformation. Each methoxy group is oriented in the same plane of the respective aromatic ring, showing torsion angles below 11.8 (3° and bond angles between the methoxy group and the aromatic ring of 116.6 (2 and 116.6 (1°. The structure shows interactions between two the N atoms of the heterocyclic ring and the hydroxy groups by intramolecular O—H...N hydrogen-bonding interactions. In the crystal, C—H...O interactions are observed. The crystal studied was a racemic mixture of RR and SS enantiomers.

  11. 4,4′-Dichloro-3,3′,5,5′-tetramethyl-2,2′-[(3aR,7aR/3aS,7aS-2,3,3a,4,5,6,7,7a-octahydro-1H-1,3-benzimidazole-1,3-diylbis(methylene]diphenol

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    Augusto Rivera


    Full Text Available In the title compound, C25H32Cl2N2O2, there are two intramolecular O—H... N hydrogen-bonding interactions between the hydroxy groups on the aromatic rings and the two N atoms of the heterocyclic group. The cyclohexane ring adopts a chair conformation and the imidazolidine unit to which it is fused has a twisted envelope conformation. The asymmetric unit comprises one half-molecule which is completed by a twofold rotation axis. A C—H...O interaction is observed in the crystal structure.

  12. 4,4′-Dibromo-2,2′-{[(3aS,7aS-2,3,3a,4,5,6,7,7a-octahydro-1H-1,3-benzimidazole-1,3-diyl]bis(methylidene}diphenol

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    Augusto Rivera


    Full Text Available The cyclohexane ring in the title compound, C21H24Br2N2O2, adopts a chair conformation and the five-membered ring to which it is fused has a twisted envelope conformation. The asymmetric unit contains one half-molecule, which is related to the other half by a twofold rotation axis. The two N atoms of the five-membered ring are linked to the hydroxy groups by intramolecular O—H...N hydrogen bonds. In the crystal, intermolecular C—H...O and C—H...π interactions occur.

  13. 4,4′-Dichloro-2,2′-[(3aR,7aR/3aS,7aS-2,3,3a,4,5,6,7,7a-octahydro-1H-1,3-benzimidazole-1,3-diylbis(methylene]diphenol

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    Michal Dušek


    Full Text Available Molecules of the the title compound, C21H24Cl2N2O2, are located on a twofold rotation axis, which passes through the C atom linking the two N atoms. Two intramolecular O—H...N hydrogen bonds were observed. In the crystal, non-classical intermolecular C—H...O hydrogen bonds link the molecules into chains along the a axis. The crystal studied was a racemic twin.

  14. Diethyl 4,4′-dihydroxy-3,3′-{[(3aRS,7aRS-2,3,3a,4,5,6,7,7a-octahydro-1H-1,3-benzimidazole-1,3-diyl]bis(methylene}dibenzoate

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    Augusto Rivera


    Full Text Available The heterocyclic ring in the title compound, C27H34N2O6, has an envelope conformation on one of the bridgehead C atoms [Q(2 = 0.4487 (19 Å and ϕ = 291.3 (2°]. Two strong intramolecular O—H...N hydrogen bonds stabilize the molecular conformation. The benzoate groups differ in the relative orientations of the ethyl groups, as quantified by the values of the C—O—C—C torsion angles of −86.5 (2 and −178.97 (17°. The carbonyl groups are nearly coplanar with the benzene rings, forming C—C—C—O torsion angles of 0.9 (3 and 3.4 (3°. The crystal structure is stabilized by weak intermolecular C—H...O interactions.

  15. meso-4,4′-Difluoro-2,2′-{[(3aR,7aS-2,3,3a,4,5,6,7,7a-octahydro-1H-1,3-benzimidazole-1,3-diyl]bis(methylene}diphenol

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    Augusto Rivera


    Full Text Available In the crystal structure of the title compound, C21H24F2N2O2, there are two intramolecular O—H...N hydrogen bonds involving the N atoms of the imidazolidine ring and the hydroxy groups. The crystal studied was a meso compound obtained by the reaction of the aminal (2S,7R,11S,16R-1,8,10,17-tetraazapentacyclo[,17.02,7.011,16]cosane with 4-fluorophenol. The imidazolidine ring has a twisted conformation with a CH—CH—N—CH2 torsion angle of 44.99 (14° and, surprisingly, the lone pairs of the N atoms are disposed in a syn isomerism, making the title compound an exception to the typical `rabbit-ear effect' in 1,2-diamines. In the crystal, molecules are linked via C—H...F hydrogen bonds, forming chains along the c-axis direction. These chains are linked via another C—H...F hydrogen bond, forming a three-dimensional network.

  16. Di-n-butyl 4,4′-dihydroxy-3,3′-{[(3aRS,7aRS-2,3,3a,4,5,6,7,7a-octahydro-1H-1,3-benzimidazole-1,3-diyl]bis(methylene}dibenzoate

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    Augusto Rivera


    Full Text Available The complete molecule of the title compound, C31H42N2O6, is generated by crystallographic twofold symmetry, with one C atom lying on the axis. The dihedral angle between the aromatic rings is 57.03 (6°. The central heterocyclic ring adopts a half-chair conformation. The molecular conformation is stabilized by two intramolecular O—H...N hydrogen bonds with the N atoms of the heterocyclic ring as the acceptors. In the crystal, molecules are linked into chains along the c axis by non-classical C—H...O hydrogen bonds.

  17. 4,4′-Difluoro-2,2′-{[(3aRS,7aRS-2,3,3a,4,5,6,7,7a-octahydro-1H-1,3-benzimidazole-1,3-diyl]bis(methylene]}diphenol

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    Augusto Rivera


    Full Text Available In the crystal structure of the title compound, C21H24F2N2O2, the two N atoms of the imidazolidine moiety are linked to the hydroxy groups by intramolecular O—H...N hydrogen-bonding interactions. The crystal studied was a racemic mixture of RR and SS enatiomers. The cyclohexane ring adopts a chair conformation and the imidazolidine group to which it is fused has a twisted envelope conformation.

  18. C-H…CI Hydrogen Bond and π-π Interaction Based Two 3D Supramolecular Architectures of Cu(Ⅱ) and Co(Ⅱ) Complexes with Chiral 1,2-Bis(benzimidazol-2-yl)ethane Ligand Containing 2D Grids

    Institute of Scientific and Technical Information of China (English)

    JI Bao-Ming; WANG Xiu-Ge; XU Chen; MA Ning; MIAO Shao-Bin


    Two new complexes, CuLCl2·2EtOH (1) and CoLCl2 (2) [L=(S,S)-1,2-bis(1-methylbenzimidazol-2-yl)-1,2-bis-(methoxy)ethane], have been synthesized in ethanol solution and structurally characterized by single crystal X-ray diffraction analysis.The crystal structure data indicated that ligand L was coordinated to copper(H) ion as a tridentate ligand using [N, N, O] atoms, while it was coordinated to cobalt(Ⅱ) ion as a bidentate ligand using [N, N] atoms.The most striking common feature of the structures of both complexes is the formation of 2D grid structures, which are formed by six and three types of intermolecular hydrogen bonds for complexes 1 and 2.These 2D grids are extended by C-H…Cl hydrogen bonds and π-π stacking interactions, leading to a 3D framework.

  19. Activities of fenbendazole in comparison with albendazole against Echinococcus multilocularis metacestodes in vitro and in a murine infection model. (United States)

    Küster, Tatiana; Stadelmann, Britta; Aeschbacher, Denise; Hemphill, Andrew


    The current chemotherapeutic treatment of alveolar echinococcosis (AE) in humans is based on albendazole and/or mebendazole. However, the costs of treatment, life-long consumption of drugs, parasitostatic rather than parasiticidal activity of chemotherapy, and high recurrence rates after treatment interruption warrant more efficient treatment options. Experimental treatment of mice infected with Echinococcus multilocularis metacestodes with fenbendazole revealed similar efficacy to albendazole. Inspection of parasite tissue from infected and benzimidazole-treated mice by transmission electron microscopy (TEM) demonstrated drug-induced alterations within the germinal layer of the parasites, and most notably an almost complete absence of microtriches. On the other hand, upon in vitro exposure of metacestodes to benzimidazoles, no phosphoglucose isomerase activity could be detected in medium supernatants during treatment with any of these drugs, indicating that in vitro treatment did not severely affect the viability of metacestode tissue. Corresponding TEM analysis also revealed a dramatic shortening/retraction of microtriches as a hallmark of benzimidazole action, and as a consequence separation of the acellular laminated layer from the cellular germinal layer. Since TEM did not reveal any microtubule-based structures within Echinococcus microtriches, this effect cannot be explained by the previously described mechanism of action of benzimidazoles targeting β-tubulin, thus benzimidazoles must interact with additional targets that have not been yet identified. In addition, these results indicate the potential usefulness of fenbendazole for the chemotherapy of AE.

  20. A survey of anthelmintic resistance on ten sheep farms in Mashonaland East Province, Zimbabwe : research communication

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    S. Mukaratirwa


    Full Text Available A survey to detect anthelmintic resistance in nematode parasites of sheep was conducted on 10 randomly-distributed farms in the Chivhu District, Mashonaland East Province, Zimbabwe. Before the survey, a questionnaire was circulated to the farmers concerning nematode parasite control. Results showed that parasite control using anthelmintic treatment was the only method practised and that the benzimidazoles were the most frequently used anthelmintic drugs. The faecal egg count reduction test was used to detect resistance. The anthelmintic groups tested were benzimidazoles, levamisole and ivermectin. Resistance to benzimidazoles was detected on 6 of 10 farms and levamisole resistance on 2 of 3 farms. Ivermectin resistance was not observed on the farms surveyed. Post-treatment larval cultures indicated that Haemonchus contortus survived administration of fenbendazole, albendazole, oxfendazole and levamisole. A Cooperia sp. strain resistant to albendazole was detected and this is the first report in Zimbabwe of a resistant parasite in this genus.