In silico and in vitro validation of some benzimidazole derivatives as adenosine deaminase inhibitors

Abstract

Benzimidazole nucleus considered as an important scaffold for developing drug candidates against a wide spectrum of diseases. Adenosine deaminase (ADA), an enzyme present in purine metabolic pathway, has a significant role in inflammatory and malignant diseases and hence it is considered as a major target for drug development. The present study investigates ADA inhibitory potential of selected benzimidazole derivatives by using in silico and in vitro methods. Molecular docking and dynamics simulations have been carried out to identify potential ADA activesite binders from benzimidazole derivatives. Compounds having strong binding affinities were selected for enzyme inhibition assays and fluorescent binding studies. The results showed that the pyridinyl and butyl derivatives of benzimidazole possess significant ADA inhibitory potential.The study proposes these compounds can be used as potent candidates for developing ADA inhibitor drugs.