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Benzimidazole-biologically attractive scaffold for protein kinase inhibitors

Singla, Prinka, Luxami, Vijay, Paul, Kamaldeep
RSC advances 2014 v.4 no.24 pp. 12422-12440
adverse effects, benzimidazole, cyclin-dependent kinase, enzyme inhibitors, hydrogen bonding, mitogen-activated protein kinase, non-specific serine/threonine protein kinase, proteins, structure-activity relationships, therapeutics, van der Waals forces
Great advances in elucidating molecular structures allow the precise determination of the interactions between a protein and a therapeutic agent. Enzyme inhibitors are used as a therapeutic agent with organic molecules, that interact with their targets through the weak linkages of hydrogen bonding and van der Waals interactions. These reduce the undesirable side effects and allow more non-specific interactions with non-target molecules. Benzimidazole acts as an enzyme inhibitor that may interact with different proteins and enzymes and has inspired chemists to carry out various structural variations of it. This review discusses the development of distinct benzimidazoles with an array of enzyme inhibitors viz., aurora kinase inhibitors, cyclin-dependent kinase inhibitors, mitogen activated protein kinase inhibitors, polo like kinase inhibitors, Tie kinase inhibitors, lymphocyte specific kinase inhibitors etc., also highlighting the molecular interaction with enzyme inhibitors. Various derivatives of benzimidazole, with different inhibitory activities, have been described on the basis of substitution around the central moiety, with an aim to help medicinal chemists to develop structure–activity relationships. The reviews in the literature till now are focused only on the biological activities of benzimidazole viz., antiviral, anticancer and antifungal, but the present review focuses on the latest work, describing the inhibitor aspects and the potential of the benzimidazole ring. This discussion will further help in the development of novel benzimidazole compounds.