A series of cis-restricted combretastatin analogues with 5-membered heterocycles were synthesized and their inhibitory activity against microtubule assembly and cytotoxic activity against the colon 26 adenocarcinoma cancer cell line were evaluated. Some of the heterocyclic analogues showed potent antitubulin activity and cytotoxicity. Compounds 16 and 35 showed marked tumor growth suppression in the colon 26 murine tumor model.