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

doi:10.1016/j.ejmech.2017.11.012

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

Research output: Contribution to journal › Article › peer-review

23 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 language	English (US)
Pages (from-to)	1-7
Number of pages	7
Journal	European Journal of Medicinal Chemistry
Volume	143
DOIs	https://doi.org/10.1016/j.ejmech.2017.11.012
State	Published - Jan 1 2018

Keywords

Azobenzene
Colchicine
Combretastatin
Photopharmacology
Tubulin

ASJC Scopus subject areas

Pharmacology
Drug Discovery
Organic Chemistry

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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 › peer-review

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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",

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

note = "Funding Information: Albion College Faculty Development Fund and the Foundation for Undergraduate Research, Scholarship, and Creative Activity (FURSCA) for funding. We thank the National Science Foundation (PREM Center for Interfaces, DMR-1205670 ) for financial support of this research. The authors also acknowledge the support of the National Science Foundation for NMR instrumentation ( CR1IF:MU-0946998 and MRI-0821254 ). ",

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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.

N1 - Funding Information: Albion College Faculty Development Fund and the Foundation for Undergraduate Research, Scholarship, and Creative Activity (FURSCA) for funding. We thank the National Science Foundation (PREM Center for Interfaces, DMR-1205670 ) for financial support of this research. The authors also acknowledge the support of the National Science Foundation for NMR instrumentation ( CR1IF:MU-0946998 and MRI-0821254 ).

PY - 2018/1/1

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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.

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