title: Synthesis, biological evaluation, and molecular docking studies of cinnamic acyl 1,3,4-thiadiazole amide derivatives as novel antitubulin agents.
abstract: A series of cinnamic acyl 1,3,4-thiadiazole amide derivatives (6a-10e) have been designed and synthesized, and their biological activities were also evaluated as potential antiproliferation and tubulin polymerization inhibitors. Among all the compounds, 10e showed the most potent activity in vitro, which inhibited the growth of MCF-7 and A549 cell lines with IC(50) values of 0.28 and 0.52μg/mL, respectively. Compound 10e also exhibited significant tubulin polymerization inhibitory activity (IC(50)=1.16μg/mL). Docking simulation was performed to insert compound 10e into the crystal structure of tubulin at colchicine binding site to determine the probable binding model. Based on the preliminary results, compound 10e with potent inhibitory activity in tumor growth may be a potential anticancer agent.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Xian-Hui
authors.initials: XH
authors.lastname: Yang
authors.forename: Qing
authors.initials: Q
authors.lastname: Wen
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Zhao
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Man
authors.initials: M
authors.lastname: Xing
authors.forename: Xiang
authors.initials: X
authors.lastname: Lu
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000577:Amides; D000970:Antineoplastic Agents; D002934:Cinnamates; D013830:Thiadiazoles; D014404:Tubulin; D050257:Tubulin Modulators; C029010:cinnamic acid; C058949:1,3,4-thiadiazole