title: Synthesis and biological evaluation of 1,9-disubstituted β-carbolines as potent DNA intercalating and cytotoxic agents.
abstract: A series of novel 1,9-disubstituted β-carbolines was designed, synthesized and evaluated as cytotoxic and DNA intercalating agents. Compounds 7b, 7c, 8b and 8c exhibited the most potent cytotoxic activities with IC(50) values of lower than 20 μM against ten human tumor cell lines. The results indicated that (1) the 3-chlorobenzyl and 3-phenylpropyl substituents in position-9 of β-carboline nucleus were the suitable pharmacophoric group giving rise to significant antitumor agents; (2) the length of the alkylamino side chain moiety affected their cytotoxic potencies, and three CH(2) units were more favorable. In addition, these compounds were found to exhibit remarkable DNA intercalating effects.
authors.affiliation: Guangdong Provincial Public Laboratory of Analysis and Testing Technology, China National Analytical Center, Building 34, 100 Xianlie Middle Road, Guangzhou, 510070, PR China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Chen
authors.forename: Rihui
authors.initials: R
authors.lastname: Cao
authors.forename: Buxi
authors.initials: B
authors.lastname: Shi
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.forename: Qin
authors.initials: Q
authors.lastname: Ma
authors.forename: Wenxi
authors.initials: W
authors.lastname: Fan
authors.forename: Huacan
authors.initials: H
authors.lastname: Song
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D002243:Carbolines; D003603:Cytotoxins; D007364:Intercalating Agents; D004247:DNA