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 substituted bivalent β -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 1 H NMR, 13 C NMR, and HRMS. The cytotoxic activities of all bivalent β -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 β -carbolines. The results demonstrated that compounds 5a ~ 5h exhibited potent cytotoxic activities with IC 50 values lower than 10 μmol·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 IC 50 values of 0.8 μmol·L -1 and 0.6 μmol·L -1 , respectively.