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 language | English (US) |
---|---|
Pages (from-to) | 1-7 |
Number of pages | 7 |
Journal | European Journal of Medicinal Chemistry |
Volume | 143 |
DOIs | |
State | Published - Jan 1 2018 |
Keywords
- Azobenzene
- Colchicine
- Combretastatin
- Photopharmacology
- Tubulin
ASJC Scopus subject areas
- Pharmacology
- Drug Discovery
- Organic Chemistry