Synthesis and antitumor activity of β-carboline 3-(substituted-carbohydrazide) derivatives

A series of beta-carboline derivatives bearing a substituted-carbohydrazide moiety at C-3 were synthesized and evaluated for their antitumor activity against eight human cancer cell lines. The beta-carboline N-(substituted-benzylidene)carbohydrazides showed, in general, a greater antitumor activity than their N-(alkylidene)carbohydrazide analogues. The N-9-methylation of beta-carboline N-(substituted-benzylidene) carbohydrazides resulted in a decrease of antitumor activity. Among compounds tested, the benzylidene-carbohydrazides 3, 4, 11, 13, 16, 21 and 22 were the most active, possessing IC50 less than 10 mu M for six of the eight tumor cell lines assayed. The derivative 4 displayed the most significant activity toward all tested cell lines, with a remarkable cytotoxicity against renal (786-0) cell lines (IC50 = 0.04 mu M). Compound 4 was assayed for its in vivo antineoplastic activity in the Ehrlich solid carcinoma assay. (C) 2011 Elsevier Ltd. All rights reserved.