Compounds 1-5, structurally related to combretastatin A-4 showed excellent cytotoxic activities against a panel of human cancer cell lines including multi-drug resistant cell lines. The X-ray three-dimensional structural analysis shows that proton donor in B ring may be required for cytotoxic activity, with intermolecular hydrogen bonding playing an important role. (C) 2002 Elsevier Science Ltd. All rights reserved.