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

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]center dot 0.4H(2)O (5), [Cu(HAPIH)Cl-2]center dot 1.25H(2)O (6), [Cu(HPAmIH)Cl-2]center dot H2O (7) and [Cu(HPzAmIH)Cl-2]center dot 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 A mu g/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 A mu M) are similar to those ones found for doxorubicin (0.23-0.43 A mu M). Complexes 5 and 6 displayed high activity against M. tuberculosis (MIC = 0.85 and 1.58 A mu M, respectively), as compared with isoniazid (MIC = 2.27 A mu M), which suggests the compounds are attractive candidates as antitubercular drugs.