Photoresponsive azo-combretastatin A-4 analogues

Shiva K. Rastogi, Zhenze Zhao, Scott L. Barrett, Spencer D. Shelton, Martina Zafferani, Hailee E. Anderson, Madeleine O. Blumenthal, Lindsey R. Jones, Lei Wang, Xiaopeng Li, Craig N. Streu, Liqin Du, William J. Brittain

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15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalEuropean Journal of Medicinal Chemistry
Volume143
DOIs
StatePublished - Jan 1 2018

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Keywords

  • Azobenzene
  • Colchicine
  • Combretastatin
  • Photopharmacology
  • Tubulin

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Rastogi, S. K., Zhao, Z., Barrett, S. L., Shelton, S. D., Zafferani, M., Anderson, H. E., Blumenthal, M. O., Jones, L. R., Wang, L., Li, X., Streu, C. N., Du, L., & Brittain, W. J. (2018). Photoresponsive azo-combretastatin A-4 analogues. European Journal of Medicinal Chemistry, 143, 1-7. https://doi.org/10.1016/j.ejmech.2017.11.012