Conformationally restricted analogs of Combretastatin A-4 derived from SU5416.
A series of compounds originally derived from the vascular endothelial growth factor receptor tyrosine kinase inhibitor, SU5416, was synthesized and evaluated. The most potent compound in this series, compound 7, structurally resembles the potent anti-microtubule agent Combretastatin A-4, inhibited tubulin polymerization, and showed potent growth inhibitory activities on both prostate and breast cancer lines with IC(50) values in low to subnanomolar range.
Li
Pui-Kai
PK
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA. li.27@osu.edu
Xiao
Zili
Z
Hu
Zhigen
Z
Pandit
Bulbul
B
Sun
Yanjun
Y
Sackett
Dan L
DL
Werbovetz
Karl
K
Lewis
Andrew
A
Johnsamuel
Jayasekar
J
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D007211:Indoles / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D011758:Pyrroles / Q000737:chemistry*; D013267:Stilbenes / Q000737:chemistry*; D013552:Swine; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism
D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D013267:Stilbenes; D014404:Tubulin; C116890:Semaxinib; C058728:fosbretabulin