Synthesis and evaluation of copper(II) complexes with isoniazid-derived hydrazones as anticancer and antitubercular agents.

Autor: Firmino GS; Departamento de Química Geral e Inorgânica, Instituto de Química, Universidade do Estado do Rio de Janeiro-UERJ, Rio de Janeiro, RJ, 20550-900, Brazil., de Souza MV; Instituto de Tecnologia em Fármacos-Farmanguinhos, Fundação Oswaldo Cruz-FioCruz, Rio de Janeiro, RJ, 21041-250, Brazil., Pessoa C; Laboratório de Oncologia Experimental, Universidade Federal do Ceará-UFC, Fortaleza, CE, 60430-270, Brazil., Lourenco MC; Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz-FioCruz, Rio de Janeiro, RJ, 21040-360, Brazil., Resende JA; Instituto de Química, Universidade Federal Fluminense-UFF, Niterói, RJ, 24020-141, Brazil.; Instituto de Ciências Exatas e da Terra, Centro Universitário do Araguaia, Universidade Federal do Mato Grosso, Barra do Garças, MT, 786000-000, Brazil., Lessa JA; Departamento de Química Geral e Inorgânica, Instituto de Química, Universidade do Estado do Rio de Janeiro-UERJ, Rio de Janeiro, RJ, 20550-900, Brazil. josane@uerj.br.
Jazyk: angličtina
Zdroj: Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine [Biometals] 2016 Dec; Vol. 29 (6), pp. 953-963. Date of Electronic Publication: 2016 Sep 03.
DOI: 10.1007/s10534-016-9968-7
Abstrakt: In this study, the N,N,O metal chelator 2-pyridinecarboxaldehydeisonicotinoyl hydrazone (HPCIH, 1) and its derivatives 2-acetylpyridine-(HAPIH 2), 2-pyridineformamide-(HPAmIH, 3) and pyrazineformamide-(HPzAmIH, 4) were employed in the synthesis of four copper(II) complexes, [Cu(HPCIH)Cl 2 ]·0.4H 2 O (5), [Cu(HAPIH)Cl 2 ]·1.25H 2 O (6), [Cu(HPAmIH)Cl 2 ]·H 2 O (7) and [Cu(HPzAmIH)Cl 2 ]·1.25H 2 O (8). The compounds were assayed for their action toward Mycobacterium tuberculosis H37Rv ATCC 27294 strain and the human tumor cell lines OVCAR-8 (ovarian cancer), SF-295 (glioblastoma multiforme) and HCT-116 (colon adenocarcinoma). All copper(II) complexes were more effective in reducing growth of HCT-116 and SF-295 cells than the respective free hydrazones at 5 µg/mL, whereas only complex 7 was more cytotoxic toward OVCAR-8 lines than its ligand HPAmIH. 6 proved to be cytotoxic at submicromolar doses, whose IC 50 values (0.39-0.86 µM) are similar to those ones found for doxorubicin (0.23-0.43 µM). Complexes 5 and 6 displayed high activity against M. tuberculosis (MIC = 0.85 and 1.58 µM, respectively), as compared with isoniazid (MIC = 2.27 µM), which suggests the compounds are attractive candidates as antitubercular drugs.
Databáze: MEDLINE
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