title: Synthesis and evaluation of copper(II) complexes with isoniazid-derived hydrazones as anticancer and antitubercular agents.
abstract: 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)Cl2]·0.4H2O (5), [Cu(HAPIH)Cl2]·1.25H2O (6), [Cu(HPAmIH)Cl2]·H2O (7) and [Cu(HPzAmIH)Cl2]·1.25H2O (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 IC50values (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.
authors: Departamento de Química Geral e Inorgânica, Instituto de Química, Universidade do Estado do Rio de Janeiro-UERJ, Rio de Janeiro, RJ, 20550-900, Brazil.
authors: Gisele S S
authors: GS
authors: Firmino
authors: Instituto de Tecnologia em Fármacos-Farmanguinhos, Fundação Oswaldo Cruz-FioCruz, Rio de Janeiro, RJ, 21041-250, Brazil.
authors: Marcus V N
authors: MV
authors: de Souza
authors: Laboratório de Oncologia Experimental, Universidade Federal do Ceará-UFC, Fortaleza, CE, 60430-270, Brazil.
authors: Claudia
authors: C
authors: Pessoa
authors: Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz-FioCruz, Rio de Janeiro, RJ, 21040-360, Brazil.
authors: Maria C S
authors: MC
authors: Lourenco
authors: 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.
authors: Jackson A L C
authors: JA
authors: Resende
authors: 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.
authors: Josane A
authors: 0000-0002-3063-7972
authors: JA
authors: Lessa
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D045325:HCT116 Cells; D006801:Humans; D006835:Hydrazones / Q000737:chemistry; D007538:Isoniazid / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013055:Spectrophotometry, Infrared
chemical_list: D000970:Antineoplastic Agents; D000995:Antitubercular Agents; D056831:Coordination Complexes; D006835:Hydrazones; D007538:Isoniazid
keywords: Anticancer agent; Antitubercular agent; Copper(II) complexes; Hydrazones; Isoniazid