2. Academic Validation
  3. Photoresponsive azo-combretastatin A-4 analogues

Photoresponsive azo-combretastatin A-4 analogues

  • Eur J Med Chem. 2018 Jan 1:143:1-7. doi: 10.1016/j.ejmech.2017.11.012.
Shiva K Rastogi 1,  Zhenze Zhao 2,  Scott L Barrett 2,  Spencer D Shelton 2,  Martina Zafferani 3,  Hailee E Anderson 2,  Madeleine O Blumenthal 2,  Lindsey R Jones 2,  Lei Wang 4,  Xiaopeng Li 4,  Craig N Streu 3,  Liqin Du 2,  William J Brittain 5
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, 601 University Drive, Texas State University, San Marcos, TX 78666, USA. Electronic address: wclskr55@txstate.edu.
  • 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: wb20@txstate.edu.
PMID: 29172077 DOI: 10.1016/j.ejmech.2017.11.012
Abstract

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.

Keywords

Azobenzene; Colchicine; Combretastatin; Photopharmacology; Tubulin.

Figures