Synthesis and structure-activity relationships of 1,2,4-triazoles as a novel class of potent tubulin polymerization inhibitors.
A novel triazole-containing chemical series was shown to inhibit tubulin polymerization and cause cell cycle arrest in A431 cancer cells with EC(50) values in the single digit nanomolar range. Binding experiments demonstrated that representative active compounds of this class compete with colchicine for its binding site on tubulin. The syntheses and structure-activity relationship studies for the triazole derivatives are described herein.
Ouyang
Xiaohu
X
Department of Chemistry, ImClone Systems, 710 Parkside Avenue, Suite 2, Brooklyn, NY 11226, USA. shawn_ouyang@yahoo.com
Chen
Xiaoling
X
Piatnitski
Evgueni L
EL
Kiselyov
Alexander S
AS
He
Hai-Ying
HY
Mao
Yunyu
Y
Pattaropong
Vatee
V
Yu
Yang
Y
Kim
Ki H
KH
Kincaid
John
J
Smith
Leon
L
Wong
Wai C
WC
Lee
Sui Ping
SP
Milligan
Daniel L
DL
Malikzay
Asra
A
Fleming
James
J
Gerlak
Jason
J
Deevi
Dhanvanthri
D
Doody
Jacqueline F
JF
Chiang
Hui-Hsien
HH
Patel
Sheetal N
SN
Wang
Ying
Y
Rolser
Robin L
RL
Kussie
Paul
P
Labelle
Marc
M
Tuma
M Carolina
MC
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008870:Microtubules / Q000187:drug effects; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D014230:Triazoles; D050257:Tubulin Modulators; C045575:1,2,4-triazole