title: Synthesis and biological evaluation of N(9)-substituted harmine derivatives as potential anticancer agents.
abstract: A series of N(9)-substituted harmine derivatives were synthesized and evaluated for their anticancer activity on a panel of cancer cell lines, their apoptosis induction and their cell cycle effects. The results showed that N(9)-substituted harmine derivatives had anticancer effects. In particular, N(9)-haloalkyl derivatives 9a-9c and N(9)-acyl harmine derivatives 11c and 11d, with IC50 values less than 1μM, were more potent than doxorubicin against A-549 and/or MCF-7 cell lines. Moreover, structure-activity relationships (SARs) indicated that introducing a haloalkyl or benzenesulfonyl group in the N(9)-position of harmine could significantly increase the anticancer activity. The most active compound (11d) caused cell cycle arrest in the G2/M phase, and induced cell apoptosis in a dose-dependent manner.
authors.affiliation: Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, Shaanxi Province, PR China; College of Plant Protection, Northwest A&F University, Yangling 712100, Shaanxi Province, PR China. Electronic address: duht@nwsuaf.edu.cn.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Du
authors.affiliation: Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, Shaanxi Province, PR China. Electronic address: stian@nwsuaf.edu.cn.
authors.forename: Shan
authors.initials: S
authors.lastname: Tian
authors.affiliation: Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, Shaanxi Province, PR China. Electronic address: cjc2009@nwsuaf.edu.cn.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Chen
authors.affiliation: Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, Shaanxi Province, PR China. Electronic address: hlgu@nwsuaf.edu.cn.
authors.forename: Hongling
authors.initials: H
authors.lastname: Gu
authors.affiliation: Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, Shaanxi Province, PR China. Electronic address: lnuk@nwsuaf.edu.cn.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, Shaanxi Province, PR China. Electronic address: wangjunru@nwsuaf.edu.cn.
authors.forename: Junru
authors.initials: J
authors.lastname: Wang
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006247:Harmine / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D061986:MCF-7 Cells; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D006247:Harmine
keywords: Anticancer activities; Apoptosis; Cell cycle arrest; Harmine derivatives; Structure–activity relationships (SARs)