Photoresponsive azo-combretastatin A-4 analogues.
Colchicine analogues in which an azo group is incorporated into a molecule containing the key pharmacophore of colchicine, have found particular utility as switchable tubulin binding chemotherapeutics. Combretastatin is a related compound containing a stilbene fragment that shows different bioactivity for the cis and trans isomers. We have performed cell assays on 17 new compounds structurally related to a previously reported azo-analogue of combretastatin. One of these compounds showed enhanced potency against HeLa (IC50 = 0.11 μM) and H157 cells (IC50 = 0.20 μM) for cell studies under 400 nm irradiation and the highest photoactivity (IC50 with irradiation/IC50 in dark = 550). We have performed docking and physicochemical studies of this new compound (7). Kinetic studies in water reveal a longer half-life for the cis isomer of 7 which may be one factor responsible for the better IC50 values in cell assays and the improved photoresponsive behavior.
['Rastogi|Shiva K|SK|', 'Zhao|Zhenze|Z|', 'Barrett|Scott L|SL|', 'Shelton|Spencer D|SD|', 'Zafferani|Martina|M|', 'Anderson|Hailee E|HE|', 'Blumenthal|Madeleine O|MO|', 'Jones|Lindsey R|LR|', 'Wang|Lei|L|', 'Li|Xiaopeng|X|', 'Streu|Craig N|CN|', 'Du|Liqin|L|', 'Brittain|William J|WJ|']
D000970:Antineoplastic Agents D001391:Azo Compounds D049109:Cell Proliferation D004305:Dose-Response Relationship, Drug D004354:Drug Screening Assays, Antitumor D006801:Humans D007700:Kinetics D008024:Ligands D015394:Molecular Structure D055668:Photochemical Processes D013267:Stilbenes D013329:Structure-Activity Relationship D014466:Ultraviolet Rays
Colchicine Tubulin Combretastatin Azobenzene Photopharmacology