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 ]·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.