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
Source: PubMed


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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    • "Benzimidazole derivatives have long been therapeutically used for the treatment of various diseases including parasitic diseases and cancer [1] [2] [3] [4]. Presently, this group of compounds has emerged as an important pharmacophore in the development of anticancer agents [4] [5] [6]. "
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    ABSTRACT: Here, we have discovered CXI-benzo-84 as a potential anticancer agent from a library of benzimidazole derivatives using cell based screening strategy. CXI-benzo-84 inhibited cell cycle progression in metaphase stage of mitosis and accumulated spindle assembly checkpoint proteins Mad2 and BubR1 on kinetochores, which subsequently activated apoptotic cell death in cancer cells. CXI-benzo-84 depolymerized both interphase and mitotic microtubules, perturbed EB1 binding to microtubules and inhibited the assembly and GTPase activity of tubulin in vitro. CXI-benzo-84 bound to tubulin at a single binding site with a dissociation constant of 1.2±0.2μM. Competition experiments and molecular docking suggested that CXI-benzo-84 binds to tubulin at the colchicine-site. Further, computational analysis provided a significant insight on the binding site of CXI-benzo-84 on tubulin. In addition to its potential use in cancer chemotherapy, CXI-benzo-84 may also be useful to screen colchicine-site agents and to understand the colchicine binding site on tubulin.
    Biochemical pharmacology 06/2013; 86(3). DOI:10.1016/j.bcp.2013.05.024 · 5.01 Impact Factor
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    • "The major reasons of this cancer are: diet poor in fiber, folate, and calcium or rich in meat and fat, smoking and high alcohol intake (Weitz et al., 2005). Benzimidazole is a heterocyclic moiety possessing a wide spectrum of biological activities; a number of its organic derivatives have shown potential anticancer activity against Leukemia (HL-60), Breast Cancer (MCF- 7), Human colon adenocarcinoma (HT-29), and Cervical cancer (HeLa) (Narasimhan et al., 2012) including a number of other therapeutic activities (Bansal and Silakari, 2012). Due to the aforementioned reasons, a number of benzimidazolium salts (organic salts, IV–VI) were synthesized , unlike organic derivatives of benzimidazole (organic compounds), in order to increase the solubility and efficacy of these heterocycles. "
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    ABSTRACT: The article describes synthesis, characterization (NMR, FT-IR, microanalysis, X-ray crystallography), in vitro anticancer, and antioxidant activity of para-xylyl linked bis-benzimidazolium salts and respective dinuclear Ag–NHC complexes. All the compounds were tested for their cytotoxicity against human colorectal cancer cells (HCT 116) and DPPH antioxidant evaluation. According to cell viability measurements using MTT assay, all the tested compounds showed dose-dependent cytotoxic activity against HCT 116 cells. The tested compounds demon-strated significant activity with IC 50 values range 0.29–3.30 lM for HCT 116 and % age inhibition 6.37–21.00 for DPPH antioxidant study. 5-Fluorouracil was used as standard drug (IC 50 19.2 lM for HCT 116) whereas for DPPH analysis, Gallic acid was used as posi-tive control (% age inhibition 77.68). All the compounds showed potential anticancer activity against human colo-rectal cancer whereas antioxidant activity was not signifi-cant. We found that as the size of N-alkyl substitution on benzimidazolium salt increases its cytotoxicity against cancer decreases whereas a reverse occurs in case of respective complexes.
    Medicinal Chemistry Research 04/2013; 22(10). DOI:10.1007/s00044-012-0461-8 · 1.40 Impact Factor
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    ABSTRACT: 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.
    International Journal of Molecular Sciences 12/2012; 13(12):16472-88. DOI:10.3390/ijms131216472 · 2.86 Impact Factor
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