Synthesis and structure--activity relationships of N²-alkylated quaternary β-carbolines as novel antitumor agents.
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.
['Zhang|Guoxian|G|', 'Cao|Rihui|R|', 'Guo|Liang|L|', 'Ma|Qin|Q|', 'Fan|Wenxi|W|', 'Chen|Xuemei|X|', 'Li|Jianru|J|', 'Shao|Guang|G|', 'Qiu|Liqin|L|', 'Ren|Zhenghua|Z|']
D000818:Animals D000970:Antineoplastic Agents D002243:Carbolines D045744:Cell Line, Tumor D049109:Cell Proliferation 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 D013329:Structure-Activity Relationship
Synthesis β-Carboline Antitumor Cytotoxic Structure–activity relationships