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

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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 IC50 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.

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Acknowledgments

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ). The authors express sincere thanks to the LDRX-UFF for the X-ray facilities and measurements.

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Authors and Affiliations

  1. Departamento de Química Geral e Inorgânica, Instituto de Química, Universidade do Estado do Rio de Janeiro-UERJ, Rio de Janeiro, RJ, 20550-900, Brazil

    Gisele S. S. Firmino & Josane A. Lessa

  2. Instituto de Tecnologia em Fármacos-Farmanguinhos, Fundação Oswaldo Cruz-FioCruz, Rio de Janeiro, RJ, 21041-250, Brazil

    Marcus V. N. de Souza

  3. Laboratório de Oncologia Experimental, Universidade Federal do Ceará-UFC, Fortaleza, CE, 60430-270, Brazil

    Claudia Pessoa

  4. Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz-FioCruz, Rio de Janeiro, RJ, 21040-360, Brazil

    Maria C. S. Lourenco

  5. Instituto de Química, Universidade Federal Fluminense-UFF, Niterói, RJ, 24020-141, Brazil

    Jackson A. L. C. Resende

  6. Instituto de Ciências Exatas e da Terra, Centro Universitário do Araguaia, Universidade Federal do Mato Grosso, Barra do Garças, MT, 786000-000, Brazil

    Jackson A. L. C. Resende

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  1. Gisele S. S. Firmino
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  2. Marcus V. N. de Souza
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Correspondence to Josane A. Lessa.

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10534_2016_9968_MOESM1_ESM.pdf

Supplementary material 1 (PDF 890 kb). Supplementary information (infrared and UV–vis spectra used for the identification of compounds, as well as X-ray crystal data of [Cu(HAPIH)Cl]Cl·H2O (6a) and [Cu(HPzAmIH)Cl2]·H2O (8a)) is available free of charge at http://link.springer.com as PDF file. CCDC 1497179 and CCDC 1497180 contain supplementary crystallographic data for 6a and 8a, respectively. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (+44) 1223- 336-033; or e-mail: deposit@ccdc.cam.ac.uk

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Firmino, G.S.S., de Souza, M.V.N., Pessoa, C. et al. Synthesis and evaluation of copper(II) complexes with isoniazid-derived hydrazones as anticancer and antitubercular agents. Biometals 29, 953–963 (2016). https://doi.org/10.1007/s10534-016-9968-7

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