title: Discovery of novel heteroarylmethylcarbamodithioates as potent anticancer agents: Synthesis, structure-activity relationship analysis and biological evaluation.
abstract: A series of new analogs based on the structure of lead compound 10 were designed, synthesized and evaluated for their in vitro anti-cancer activities against four selected human cancer cell lines (HL-60, Bel-7402, SK-BR-3 and MDA-MB-468). Several synthesized compounds exhibited improved anti-cancer activities comparing with lead compound 10. Among them, 1,3,4-oxadiazole analogs 17o showed highest bioactivity with IC50 values of 1.23, 0.58 and 4.29 μM against Bel-7402, SK-BR-3 and MDA-MB-468 cells, respectively. It is noteworthy that 17o has potent anti-proliferation activity toward a panel of cancer cells with relatively less cytotoxicity to nonmalignant cells. The further mechanistic study showed that it induced apoptosis and cell cycle arrest through disrupting spindle assembly in mitotic progression, indicating these synthesized dithiocarbamates represented a novel series of anti-cancer compounds targeting mitosis.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
authors.forename: Ying-Bo
authors.initials: YB
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
authors.forename: Xu
authors.initials: X
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
authors.forename: Ri-Dong
authors.initials: RD
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
authors.forename: Shao-Qian
authors.initials: SQ
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
authors.forename: Jing-Rong
authors.initials: JR
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China. Electronic address: deminzhou@bjmu.edu.cn.
authors.forename: De-Min
authors.initials: DM
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China. Electronic address: zmge@bjmu.edu.cn.
authors.forename: Ze-Mei
authors.initials: ZM
authors.lastname: Ge
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
authors.forename: Run-Tao
authors.initials: RT
authors.lastname: Li
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D010069:Oxadiazoles / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D010069:Oxadiazoles; D013859:Thiocarbamates; C583463:1,3,4-oxadiazole
keywords: 1,3,4-Oxadiazole; Anti-tumor activity; Cell cycle arrest; Dithiocarbamate; Structure-activity relationship