Design, synthesis and biological evaluation of (E)-2-(2-arylhydrazinyl)quinoxalines, a promising and potent new class of anticancer agents.

Autor: Rodrigues FA; Laboratório de Oncologia Experimental, Universidade Federal do Ceará, Fortaleza, CE, Brazil., Bomfim Ida S; Laboratório de Oncologia Experimental, Universidade Federal do Ceará, Fortaleza, CE, Brazil., Cavalcanti BC; Laboratório de Oncologia Experimental, Universidade Federal do Ceará, Fortaleza, CE, Brazil., Pessoa Cdo Ó; Laboratório de Oncologia Experimental, Universidade Federal do Ceará, Fortaleza, CE, Brazil., Wardell JL; FioCruz-Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Far-Manguinhos, Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil; Department of Chemistry, University of Aberdeen, Old Aberdeen AB 24 3UE, Scotland, UK., Wardell SM; CHEMSOL, 1 Harcourt Road, Aberdeen AB15 5NY, Scotland, UK., Pinheiro AC; FioCruz-Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Far-Manguinhos, Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil., Kaiser CR; Programa de Pós-Graduação em Química, Instituto de Química, Universidade Federal do Rio de Janeiro, CP 68563, 21945-970 Rio de Janeiro, Brazil., Nogueira TC; FioCruz-Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Far-Manguinhos, Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil; Programa de Pós-Graduação em Química, Instituto de Química, Universidade Federal do Rio de Janeiro, CP 68563, 21945-970 Rio de Janeiro, Brazil., Low JN; Department of Chemistry, University of Aberdeen, Old Aberdeen AB 24 3UE, Scotland, UK., Gomes LR; REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto, Rua Campo Alegre, 687, P-4169-007, Porto P-4200-150, Portugal., de Souza MV; FioCruz-Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos-Far-Manguinhos, Rua Sizenando Nabuco, 100, Manguinhos, 21041-250 Rio de Janeiro, RJ, Brazil. Electronic address: marcos_souza@far.fiocruz.br.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2014 Feb 01; Vol. 24 (3), pp. 934-9. Date of Electronic Publication: 2013 Dec 25.
DOI: 10.1016/j.bmcl.2013.12.074
Abstrakt: A series of forty-seven quinoxaline derivatives, 2-(XYZC6H2CHN-NH)-quinoxalines, 1, have been synthesized and evaluated for their activity against four cancer cell lines: potent cytotoxicities were found (IC50 ranging from 0.316 to 15.749 μM). The structure-activity relationship (SAR) analysis indicated that the number, the positions and the type of substituents attached to the aromatic ring are critical for biological activity. The activities do not depend on the electronic effects of the substituents nor on the lypophilicities of the molecules. A common feature of active compounds is an ortho-hydroxy group in the phenyl ring. A potential role of these ortho-hydroxy derivatives is as N,N,O-tridentate ligands complexing with a vital metal, such as iron, and thereby preventing proliferation of cells. The most active compound was (1: X,Y=2,3-(OH)2, Z=H), which displayed a potent cytotoxicity comparable to that of the reference drug doxorubicin.
(Copyright © 2013 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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