Synthesis and anticancer activities of polymethylenedioxy analogues of combretastatin A-2

Combretastatin A-4 is a highly potent natural stilbene that can inhibit cancer cell proliferation. Numerous analogues of combretastatin A-4 have been proposed for clinical applications. However, structural studies of combretastatin A-2, a methylenedioxy derivative of combretastain A-4, are not available. In this study, various analogues of combretastatin A-2 with polymethylenedioxy spacer were prepared and their antiproliferative activities to four human cancer cell lines (HeLa, SK-OV-3, A549, and HT-29) and two normal cells (HaCaT and MDCK) were evaluated. Binding characteristics were evaluated based on computational docking and previously reported experimental data. Results suggest that their binding conformations are highly dependent on steric volume and electrostatic properties of substituents.