Synthesis and structure–activity relationships of N2-alkylated quaternary β-carbolines as novel antitumor agents

• A series of N2-alkylated quaternary β-carbolines was synthesized.
• SARs of this class of compounds as antitumor agents were well studied.
• Appropriate substituents in position-2 and 9 facilitated antitumor activities.
• Compound 3m were found to be the most potent antitumor agent.

A series of novel N2-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.

A series of novel N2-alkylated quaternary β-carbolines was synthesized and evaluated as antitumor agents. 3m were found to be the most potent compound.Figure optionsDownload as PowerPoint slide