Synthesis and in vitro antitumor activity of substituted quinazoline and quinoxaline derivatives: search for anticancer agent.

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.

Comprehensive Review in Current Developments of Benzimidazole-Based Medicinal Chemistry.

Synthesis and anticancer evaluation of novel 2-cyclopropylimidazo[2,1-b][1,3,4]-thiadiazole derivatives.

The aim of this review is to provide an overview on diverse pharmacological activities of the benzimidazole moiety. This review highlights recent reports of antimicrobial, anticancer, antiviral, antiparasitic, antihypertensive as well as anti-inflammatory activities of the benzimidazoles. The purpose of this review is to collate the literature work reported by researchers on benzimidazole for its various pharmacological activities and also report recent efforts made on this moiety.

Benzimidazole: a promising pharmacophore

Lymphocyte-specific protein tyrosine kinase (Lck) inhibitors have treatment potential for autoimmune diseases and transplant rejection. A support vector machine (SVM) model trained with 820 positive compounds (Lck inhibitors) and 70 negative compounds (Lck noninhibitors) combined with 65 142 generated putative negatives was developed for predicting compounds with a Lck inhibitory activity of IC50 ≤ 10 μM. The SVM model, with an estimated sensitivity of greater than 83% and specificity of greater than 99%, was used to screen 168 014 compounds in the MDDR and was found to have a yield of 45.8% and a false positive rate of 0.52%. The model was also able to identify novel Lck inhibitors and distinguish inhibitors from structurally similar noninhibitors at a false positive rate of 0.27%. To the best of our knowledge, the SVM model developed in this work is the first model with a broad applicability domain and low false positive rate, which makes it very suitable for the virtual screening of chemical libraries ...

SVM model for virtual screening of Lck inhibitors.

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

Protein tyrosine kinase (p56 lck ) is known for its role in T cells, in which deficiency of Lck is shown to impair cell activation via T-cell antigen receptor. Benzothiazoles have been reported to be the molecules of interest, with potent anticancer activity and they act by binding to ATP binding site of protein kinases. ATP binding site of protein kinases provided an extensive opportunity to design newer analogs. With this background, we report an attempt to discern the structural and physicochemical requirements for inhibition of p56 lck . QSAR studies were performed on a set of 45 analogs of benzothiazole s using Molecular Operating Environment (MOE) software. The models developed gave good predictive correlation coefficient (r 2 pred) of 0.765. A training set of 35 compounds was developed with correlation coefficient (r 2 ) of 0.983 and a significant cross validated correlation coefficient (q 2 ) of 0.723. Various sets of descriptors to meet the orthogonality of model to ensure that each descriptor is encoding different properties from others were used. Subdivided surface area, water accessible surface area, partial charge and adjacency and distance matrix were the major contributing descriptors. Leave one out and $ Z-score values were used to optimize the model. The model developed to predict the structural features of benzothiazole , revealed useful information about the structural features required for the molecules to inhibit p56 lck . Major contributing descriptors were subdivided surface area, partial charges and water accessible surface area.

Aravind M. Badiger

Papers

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

QSAR Study of Benzothiazole Derivatives as p56lck Inhibitors