Design, Synthesis and Biological Evaluation of Novel Benzimidazole Derivatives As Anti-Cancer Agents

Abstract

Phosphatidylinositol-3 kinase (PI3K), family of lipid enzyme are major coordinators for cellular signalling pathways. Phosphatidylinositol-3 kinase serves as fundamental intracellular functions such as cell growth, differentiation, proliferation, motility which are involved intreatment of cancer, especially breast cancer. Idelalisib, Duvelisib, Copanlisib and Alpelisib are current four FDA approved PI3K inhibitors characterized as promising molecular target for novel anticancer molecules. The fusion of selective PI3K inhibitors with enzymes is marked as productive strategy to control PI3K inhibitors resistance. This combination helps in effective cancer inhibition by replacing anti-tumor responses that may certainly act as promising cancer target. In order to design novel PI3K inhibitors, the bioisosteric replacement approach was introduced to the imidazo-pyridine ring through which benzimidazole scaffold was preferred as a key moiety. Total seven designed compounds were evaluated for in silico ADMET parameters. Among them, synthesis of three novel benzimidazole derivatives was performed and characterized using analytical methods as FT- IR, MASS, 1H and 13C NMR. To examine the potency of synthesized derivatives, in vitro study on breast cancer cell line (MDA-MB-231) will be carried out using MTT assay