title: Synthesis, molecular modeling and biological evaluation of dithiocarbamates as novel antitubulin agents.
abstract: 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.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Qian
authors.forename: Gao-Yuan
authors.initials: GY
authors.lastname: Ma
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Kui
authors.initials: K
authors.lastname: Cheng
authors.forename: Qing-Zhong
authors.initials: QZ
authors.lastname: Zheng
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Mao
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: 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
chemical_list: C552762:3-(4-chlorophenyl)-3-oxo-1-phenylpropyl diethylcarbamodithioate; D005028:Ethylenebis(dithiocarbamates); D013859:Thiocarbamates; D014404:Tubulin; D050257:Tubulin Modulators; D002599:Chalcone