Synthesis of combretastatin analogs: evaluation of in vitro anticancer activity and molecular docking studies

Abstract

This study is based on the synthesis of a series of combretastatin analogs with different substitutions on one aryl moiety and a carboxylic group in connecting chain. Cis-configuration with respect to aryl groups was established by X-ray crystal analysis. All the synthesized compounds were evaluated for anticancer activity against a panel of cell lines. Six compounds 1a, 1b, 1c, 1k, 1n, and 1p showed marked anticancer activity against human colon (colo-205), lung (A549), ovary (IGROV-1), prostrate (PC-3), CNS (SF-295), leukemia (THP-1), and breast (MCF-7) cell lines. Out of these, 1b showed remarkable inhibitory activity comparable to paclitaxel against lung cancer cell line with IC50 3.9 μM. Importance of carboxylic group in the synthesized compounds was studied by flexible docking study of 1b which showed the importance of carboxylic group interactions with colchicine-binding site of αβ-tubulin. A series of combretastatin analogs have been synthesized by condensation of phenyl acetic acid and different substituted aldehydes. All the synthesized compounds were evaluated for anticancer activity against a panel of cell lines. Six compounds 1a, 1b, 1c, 1k, 1n, and 1p showed better anticancer activity against human colon (colo-205), lung (A549), ovary (IGROV-1), prostrate (PC-3), CNS (SF-295), leukemia (THP-1), and breast (MCF-7) cell lines. Out of these, 1b showed marked inhibitory activity against lung cancer cell line with IC50 3.9 μM.