title: Synthesis and structure--activity relationships of N²-alkylated quaternary β-carbolines as novel antitumor agents.
abstract: A series of novel N(2)-alkylated quaternary β-carbolines was synthesized by modification of position-1, 2, 7 and 9 of β-carboline nucleus with various alkyl and arylated alkyl substituents, and their cytotoxic activities in vitro and antitumor potencies in mice were evaluated. Compound 3m was found to be the most potent antitumor agent. SARs analysis revealed that (1) the substituents in position-2 and 9 of β-carboline nucleus played a vital role in modulation of antitumor activity; (2) the benzyl and 3-phenylpropyl substituents in position-2 and 9 of β-carboline ring were the optimal substituents giving rise to significant antitumor agent. These compounds might be a novel promising class of antitumor agents with clinical development potential.
authors.affiliation: School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
authors.forename: Guoxian
authors.initials: G
authors.lastname: Zhang
authors.forename: Rihui
authors.initials: R
authors.lastname: Cao
authors.forename: Liang
authors.initials: L
authors.lastname: Guo
authors.forename: Qin
authors.initials: Q
authors.lastname: Ma
authors.forename: Wenxi
authors.initials: W
authors.lastname: Fan
authors.forename: Xuemei
authors.initials: X
authors.lastname: Chen
authors.forename: Jianru
authors.initials: J
authors.lastname: Li
authors.forename: Guang
authors.initials: G
authors.lastname: Shao
authors.forename: Liqin
authors.initials: L
authors.lastname: Qiu
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Ren
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D002243:Carbolines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D056945:Hep G2 Cells; D006801:Humans; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D061986:MCF-7 Cells; D051379:Mice; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002243:Carbolines
keywords: Antitumor; Cytotoxic; Structure–activity relationships; Synthesis; β-Carboline