Synthesis and Antitumor Activities of Novel Bivalent 1-Heterocyclic-β-carbolines Linked by Alkylamino Spacer

In order to find novel antitumor candidate compounds with high efficiency and low toxicity, a series of 1-heterocyclic substitutedbivalent beta-carbolines with a spacer of four or five methylene units between the two 3-methylamino group were synthesized, and the chemical structures were characterized by H-1 NMR, C-13 NMR, and HRMS. The cytotoxic activities of all bivalent beta-carbolines were evaluated in vitro against a panel of human tumor cell lines (22RV1, SK-OV-3, MCF-7, LLC, Eca-109, BGC-823, HT-29, HepG-2, A375, and 769-P) and compared with the positive control cisplatin and monovalent beta-carbolines. The results demonstrated that compounds 5a similar to 5h exhibited potent cytotoxic activities with IC50 values lower than 10 umol.L-1. In particular, compounds 5d and 5h, both of which had a spacer of five methylene units, exhibited significant inhibitory activity against 769-P and 22RV1 with IC50 values of 0.8 umol.L-1 and 0.6 urnol.L-1, respectively.