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 journalArticle

9 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Colchicine
Isomers
Inhibitory Concentration 50
Assays
Irradiation
Stilbenes
Tubulin
Bioactivity
Molecules
Kinetics
Water
Half-Life
fosbretabulin
combretastatin

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., ... 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

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 journalArticle

Rastogi, SK, Zhao, Z, Barrett, SL, Shelton, SD, Zafferani, M, Anderson, HE, Blumenthal, MO, Jones, LR, Wang, L, Li, X, Streu, CN, Du, L & Brittain, WJ 2018, 'Photoresponsive azo-combretastatin A-4 analogues', European Journal of Medicinal Chemistry, vol. 143, pp. 1-7. https://doi.org/10.1016/j.ejmech.2017.11.012
Rastogi SK, Zhao Z, Barrett SL, Shelton SD, Zafferani M, Anderson HE et al. Photoresponsive azo-combretastatin A-4 analogues. European Journal of Medicinal Chemistry. 2018 Jan 1;143:1-7. https://doi.org/10.1016/j.ejmech.2017.11.012
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. / Photoresponsive azo-combretastatin A-4 analogues. In: European Journal of Medicinal Chemistry. 2018 ; Vol. 143. pp. 1-7.
@article{1e51f596f1774001bc4d4627a17078e4,
title = "Photoresponsive azo-combretastatin A-4 analogues",
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.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.ejmech.2017.11.012",
language = "English (US)",
volume = "143",
pages = "1--7",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",

}

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 -