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 lM. 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 ab-tubulin.