Design, Synthesis and Cytotoxicity Evaluationof New 1,2-diaryl-4, 5, 6, 7-Tetrahydro-1H-benzo[d] Imidazolesas Tubulin Inhibitors

Document Type: Research article

Authors

1 1Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran/Iran

2 Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran/Iran

3 Department of Pharmaceutical Biotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan/ Iran

4 Shahid Beheshti Univ. Med. Sci.

Abstract

A new series of 1,2-diaryl-4,5,6,7-tetrahydro-1H-benzo[d]imidazoles, possessing trimethoxy phenyl pharmacophore, were synthesized to evaluate their biological activities as tubulin inhibitors. Cytotoxic activity of the synthesized compounds 7a-f was assessed against several human cancer cell lines, including MCF-7 (breast cancer cell), HEPG2 (liver hepatocellular cells), A549 (adenocarcinomic human alveolar basal epithelial cells), T47D (Human ductal breast epithelial tumor cell line) and fibroblast. َAccording to our results, HEPG2 seems to be the most sensitive, while MCF7 was the most resistant cell line to the compounds. All the compounds expect 7b, possessed satisfactory activity against HEPG2 with mean IC50 values raging from 15.60 to 43.81 µM. Docking simulation was performed to position these compounds into colchicine binding site to determine the probable binding model, which suggested the possible inhibition mechanism.

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