Design and Synthesis of Benzimidazole Derivatives as Anticancer Agents

Abstract

The phosphoinositide 3-kinase (PI3K) pathway is located within a cell or cells that has major role in cell proliferation, differentiation, motility, and also in progression of cancer. . Of the eight isoforms of PI3K Class I is the best characterized class which is implicated in the various dieses mostly seen in the cancer, inflammation, autoimmunity. The therapeutic effects of PI3K inhibition has been observed in selected tumor models, and its inhibition may present a dependable therapeutic assistance. In course of this research work to design novel PI3K inhibitors, computational approach was used. 3D-QSAR was carried on imidazo [1,2-a]pyrimidine-5(1H)-ones and 1,2,4 triazolo[1,5-a]pyrimidin-7(3H)-ones model suggested that by substituting hydrophobic, bulky and electronegative groups, potency of the compound could be improved. The benzimidazole ring which is a bio-isostere of imidazo-pyridine ring, was selected as a core moiety. Designed benzimidazole derivatives were docked into active site of PI3K kinase and In-Silico ADMET properties were also predicted. Synthesis of top 7 benzimidazole derivatives was carried out and spectral characterization was carried out using Mass, 1H and 13C-NMR spectroscopy. From the Computational approaches and spectral characterization it can been concluded that the compound was synthesized and pure.