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

Abstract

A series of β-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 β-carboline N-(substituted-benzylidene)carbohydrazides showed, in general, a greater antitumor activity than their N-(alkylidene)carbohydrazide analogues. The N(9)-methylation of β-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 IC(50) less than 10 μM 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 (IC(50)=0.04 μM). Compound 4 was assayed for its in vivo antineoplastic activity in the Ehrlich solid carcinoma assay.

• Authors: Valéria Aquilino Barbosa, Anelise S Nazari Formagio, Franciele Cristina Savariz, Mary Ann Foglio, Humberto Moreira Spindola, João Ernesto de Carvalho, Emerson Meyer, Maria Helena Sarragiotto
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 19 Issue 21 Pg. 6400-8 (Nov 01 2011) ISSN: 1464-3391 [Electronic] England
• PMID: 21944971 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Carbolines

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Carbolines (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Humans
• Inhibitory Concentration 50
• Magnetic Resonance Spectroscopy
• Molecular Structure
• Spectrometry, Mass, Electrospray Ionization
• Spectrophotometry, Infrared
• Structure-Activity Relationship