Design, synthesis of N9- acyl substituted β-carboline derivatives containing 5-phenyl-2-furan moiety as potent anticancer agents

Abstract

β-Carbolines are of great interest due to their broad spectrum of biochemical effects and pharmaceutical functions, especially antitumor activity. The N9 position at β-carboline is a modification site for important antitumor activity. Several phenylfuran derivatives displayed significant antitumor activity in our previous work. Here, we designed and preparated a series of novel N9-acyl substituted β-carboline derivatives containing 5-phenyl-2-furan moiety as potent anticancer agents. All newly synthesized compounds and β-carboline were evaluated for antitumor activity on five cancer cells. β-Carboline had only weak antitumor activity, while the introduction of the phenylfuran fragment significantly improved the activity. The primary structure–activity relationship study showed that 4-substituted phenylfuran played a key role in anti-cancer activity and compound 8 displayed superior than Camptothecin in anti-proliferative activity against breast cancer cells MCF-7. Flow cytometry studied revealed that compounds 8 and 15 effectively mediated MCF-7 apoptosis. This study lays a working foundation for the research and development of new broad-spectrum antitumor drugs based on β-carboline and phenylfurans, compound 8 would be great promise as a hit antitumor candidate in the future study.

Keywords

• Design, anti-tumor agent
• β-Carbolines
• Phenylfurans
• Cell apoptosis