The therapeutic journey of benzimidazoles: A review
Molecular Modelling Lab (MML), Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab 147002, India. Bioorganic & medicinal chemistry
(Impact Factor: 2.79).
09/2012; 20(21):6208-36. DOI: 10.1016/j.bmc.2012.09.013
Presence of benzimidazole nucleus in numerous categories of therapeutic agents such as antimicrobials, antivirals, antiparasites, anticancer, anti-inflammatory, antioxidants, proton pump inhibitors, antihypertensives, anticoagulants, immunomodulators, hormone modulators, CNS stimulants as well as depressants, lipid level modulators, antidiabetics, etc. has made it an indispensable anchor for development of new therapeutic agents. Varied substitutents around the benzimidazole nucleus have provided a wide spectrum of biological activities. Importance of this nucleus in some activities like, Angiotensin I (AT(1)) receptor antagonism and proton-pump inhibition is reviewed separately in literature. Even some very short reviews on biological importance of this nucleus are also known in literature. However, owing to fast development of new drugs possessing benzimidazole nucleus many research reports are generated in short span of time. So, there is a need to couple the latest information with the earlier information to understand the current status of benzimidazole nucleus in medicinal chemistry research. In the present review, various derivatives of benzimidazole with different pharmacological activities are described on the basis of substitution pattern around the nucleus with an aim to help medicinal chemists for developing an SAR on benzimidazole derived compounds for each activity. This discussion will further help in the development of novel benzimidazole compounds.
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- "Antimicrobial activity of 6 was lower or comparable with those presented by AgNO 3. Silver N-heterocyclic carbene complexes are widely described in the literature as effective antibacterial, antifungal, and antiviral agents. Haque et al. synthesized dinuclear silver complexes with N-heterocyclic carbene, which possessed good antibacterial activity. The authors also demonstrated that compounds containing benzimidazole moiety exhibited significantly higher activity than complexes with imidazole. "
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ABSTRACT: 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.
- "For the last 40 years, serious efforts have been made to design and synthesize potential chemotherapeutic agents for anticancer therapy[2,3]. Benzimidazole derivatives have been reported to exhibit antibacterial, antiviral, antiparasitic, anthelmintic , antitumor, anti-inflammatory, antioxidant, antiulcer, antihypertensive, anticoagulant, antidepressant, anticonvulsant , antihistaminic, antiasthmatic, and antidiabetic activities4567. Recently, some benzimidazoles have also been found to have remarkable antileukemic activities8910111213. It is known that Hoechst 33342 and 33258 (Figure 1) are adenine-thymine-specific dyes that stain DNA by binding to its minor groove. "
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ABSTRACT: A series of novel 5-(4-methylpiperazin-1-yl)-2-phenyl-1H-benzimidazoles (5-14) were synthesized and evaluated for their in vitro antiproliferative activities against the human leukemia cell line HL-60. Compounds 5-7 and 10-12 exhibited potent antiproliferative activities against this cell line. The quantitative analysis of apoptosis by flow cytometry demonstrated that the percentages of apoptotic HL-60 cells treated with compounds 5 and 10-12 were significantly higher than in the control.
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- "Several benzophenones are under study; combretastatin A-4 is known to exhibit antiangiogenic effects and is being studied in clinical trials (Tozer et al., 2008). The presence of a benzimidazole nucleus in numerous categories of therapeutic agents has made it an indispensable anchor for the development of new antiangiogenic therapeutics (Yogita and Silakari, 2012). Previously, we reported the synthesis and antitumor and antiangiogenic properties of (2- aroyl-4-methylphenoxy)acetamides 4a–e, which are benzophenone analogs (Prabhakar et al., 2006a, 2006b). "
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ABSTRACT: The development of anticancer drugs with specific targets is of prime importance in modern biology. This study investigates the angiopreventive and in vivo tumor inhibition activities of novel synthetic benzophenone-benzimidazole analogs.
The multistep synthesis of novel benzophenone-benzimidazole analogs (8a-n) allowing substitution with methoxy, methyl and halogen groups at different positions on the identical chemical backbone and the variations in the number of substituents were synthesized and characterized. The newly synthesized compounds were further evaluated for cytotoxic and antiproliferative effects against Ehrlich ascites carcinoma (EAC) cells. The potent lead compounds were further assessed for antiangiogenic effects in a CAM model and a tumor-induced vasculature in vivo model. The effect of angioprevention on tumor growth was verified in a mouse model.
The cytotoxicity studies revealed that compounds 8f and 8n are strongly cytotoxic. Analyzing the structure-activity relationship, we found that an increase in the number of methyl groups in addition to methoxy substitution at the para position of the benzoyl ring in compound 8n resulted in higher potency compared to 8f. Furthermore, neovessel formation in in vivo systems, such as the chorioallantoic membrane (CAM) and tumor-induced mice peritoneum models, was significantly suppressed and reflected the tumor inhibition observed in mice.
These results suggest the potential clinical application of compound 8n as an antiangiogenic drug for cancer therapy.
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