Photoresponsive azo-combretastatin A-4 analogues
- Eur J Med Chem. 2018 Jan 1:143:1-7. doi: 10.1016/j.ejmech.2017.11.012.
- 1. Department of Chemistry and Biochemistry, 601 University Drive, Texas State University, San Marcos, TX 78666, USA. Electronic address: [email protected].
- 2. Department of Chemistry and Biochemistry, 601 University Drive, Texas State University, San Marcos, TX 78666, USA.
- 3. Department of Chemistry, Albion College, 611 E. Porter Str., Albion, MI 49224, USA.
- 4. Chemistry Department, University of South Florida, Tampa, FL 33620, USA.
- 5. Department of Chemistry and Biochemistry, 601 University Drive, Texas State University, San Marcos, TX 78666, USA. Electronic address: [email protected].
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.