Synthesis, molecular modeling and biological evaluation of dithiocarbamates as novel antitubulin agents.
A series of novel dithiocarbamate compounds with the chalcone scaffold have been designed and synthesized, and their biological activities were also evaluated as potential antiproliferation and antitubulin polymerization inhibitors. Compound 2n showed the most potent biological activity in vitro, which inhibited the growth of MCF-7 cells with IC(50) of 0.04+/-0.01 microM and the polymerization of tubulin with IC(50) of 6.8+/-0.6 microM. To understand the tubulin-inhibitor interaction and the selectivity of the most active compound towards tubulin, molecular modeling studies were performed to dock compound 2n into the colchicine binding site, which suggested probable inhibition mechanism.
Qian
Yong
Y
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Ma
Gao-Yuan
GY
Yang
Ying
Y
Cheng
Kui
K
Zheng
Qing-Zhong
QZ
Mao
Wen-Jun
WJ
Shi
Lei
L
Zhao
Jing
J
Zhu
Hai-Liang
HL
D001665:Binding Sites; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D002599:Chalcone / Q000737:chemistry; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D005028:Ethylenebis(dithiocarbamates) / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D013859:Thiocarbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
C552762:3-(4-chlorophenyl)-3-oxo-1-phenylpropyl diethylcarbamodithioate; D005028:Ethylenebis(dithiocarbamates); D013859:Thiocarbamates; D014404:Tubulin; D050257:Tubulin Modulators; D002599:Chalcone