Design, Synthesis and Anticancer Activity Studies of Novel Quinoline-Indole Derivatives

As the continuation of our studies on novel and effective anti-cancer agents, a series of novel quinoline-indole derivatives were firstly designed and synthesized by molecular hybridization strategy and Lewis acid-catalyzed coupling reactions. Their antiproliferative potency on gastric cancer cell line MGC-803, colon cancer cell line HCT-116, and esophageal cancer cell line Kyse450 of all the targeted compounds was explored using methyl thiazolyl tetrazolium (MTT) assay. 2-Chloro-4-(5-methoxy-1H-indol-3-yl)quinoline (9b) exhibited potently inhibitory activity against MGC-803, HCT-116, and Kyse450 cells with IC50 values of 0.58, 0.68 and 0.59 mu mol.L-1. Further mechanism studies suggested that compound 9b inhibited the cell colony formation of MGC-803 and HGC-27 cells. Compound 9b induced an intrinsic apoptosis and down-regulated the levels of apoptosis related proteins in MGC-803 and HGC-27 cells. Meanwhile, compound 9b arrested MGC-803 and HGC-27 cells at the G2/M phase. Taken together, these results indicated that compound 9b might be a valuable lead compound for anticancer agents.

Automated summary

A series of novel quinoline-indole derivatives were designed and synthesized, among which compound 9b exhibited potent inhibitory activity against various cancer cell lines. Mechanism studies showed that compound 9b exerted its anticancer effects through inducing apoptosis, down-regulating apoptosis-related proteins, and arresting cells at G2/M phase.