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 |
| Externally published | Yes |
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Keywords
- Azobenzene
- Colchicine
- Combretastatin
- Photopharmacology
- Tubulin
ASJC Scopus subject areas
- Pharmacology
- Drug Discovery
- Organic Chemistry
Cite this
Photoresponsive azo-combretastatin A-4 analogues. / Rastogi, Shiva K.; Zhao, Zhenze; Barrett, Scott L.; Shelton, Spencer D.; Zafferani, Martina; Anderson, Hailee E.; Blumenthal, Madeleine O.; Jones, Lindsey R.; Wang, Lei; Li, Xiaopeng; Streu, Craig N.; Du, Liqin; Brittain, William J.
In: European Journal of Medicinal Chemistry, Vol. 143, 01.01.2018, p. 1-7.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Photoresponsive azo-combretastatin A-4 analogues
AU - Rastogi, Shiva K.
AU - Zhao, Zhenze
AU - Barrett, Scott L.
AU - Shelton, Spencer D.
AU - Zafferani, Martina
AU - Anderson, Hailee E.
AU - Blumenthal, Madeleine O.
AU - Jones, Lindsey R.
AU - Wang, Lei
AU - Li, Xiaopeng
AU - Streu, Craig N.
AU - Du, Liqin
AU - Brittain, William J.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
KW - Azobenzene
KW - Colchicine
KW - Combretastatin
KW - Photopharmacology
KW - Tubulin
UR - http://www.scopus.com/inward/record.url?scp=85034569908&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85034569908&partnerID=8YFLogxK
U2 - 10.1016/j.ejmech.2017.11.012
DO - 10.1016/j.ejmech.2017.11.012
M3 - Article
C2 - 29172077
AN - SCOPUS:85034569908
VL - 143
SP - 1
EP - 7
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
ER -