Synthesis, Molecular Modeling and Biological Studies of Novel 1-Aryl-Thiazolo Benzimidazole Derivatives as Cytochrome (CYP51 MTb ) Type I Inhibitors & Anticancer Agents

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Abstract The prominent biological activity of polycyclic systems inspired the synthesis of novel 1-Aryl-thiazolo-benzimidazole Derivatives (2a-e), (3a-e) and (4a-e). In vitro antiproliferative assay was performed on colorectal adenocarcinoma (SW620) and the novel compounds showed superior anticancer activity with IC50 in the range of 0.03–0.35 µM compared to reference compound Doxorubicin (DOX) with IC50 (0.07 µM). The ability of the new molecules to interact with extracted cytochrome CYP51MTb was also studied using absorption spectroscopy. Results showed mild type I spectral shift especially compound 4d displayed 3% shift in the spin state assay referring to the presence of electron withdrawing groups attached to benzene ring, thus that could be a promising nucleus for better cytochrome inhibition. The results were supported by molecular modeling studies to confirm general binding of the compounds to the hydrophobic region of the heme-protein. These outcomes encourage the new molecules to be candidates for new potential anticancer agents.

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