Hydroxyquinoline derived vanadium(IV and V) and copper(II) complexes as potential anti-tuberculosis and anti-tumor agents
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Several mixed ligand vanadium and copper complexes were synthesized containing 8-hydroxyquinoline (8HQ) and a ligand such as picolinato (pic(-)), dipicolinato (dipic(2-)) or a Schiff base. The complexes were characterized by spectroscopic techniques and by single-crystal X-ray diffraction in the case of [(VO)-O-V(L-pheolnaph-im)(5-Cl-8HQ)] and [(VO)-O-V(OMe)(8HQ)(2)], which evidenced the distorted octahedral geometry of the complexes. The electronic absorption data showed the presence of strong ligand to metal charge transfer bands, significant solvent effects, and methoxido species in methanol, which was further confirmed by V-51- NMR spectroscopy. The structures of [Cu-II(dipic)(8HQ)]Na and [(VO)-O-IV(pic)(8HQ)] were confirmed by EPR spectroscopy, showing only one species in solution. The biological activity of the compounds was assessed through the minimal inhibitory concentration (MIC) of the compounds against Mycobacterium tuberculosis (Mtb) and the cytotoxic activity against the cisplatin sensitive/resistant ovarian cells A2780/A2780cisR and the non-tumorigenic HEK cells (IC50 values). Almost all tested vanadium complexes were very active against Mtb and the MICs were comparable to, or better than, the MICs of drugs, such as streptomycin. The activity of the complexes against the A2780 cell line was dependent on incubation time presenting IC50 values in the 3-14 mu M (at 48 h) range. In these conditions, the complexes were significantly (*P < 0.05-**P < 0.001) more active than cisplatin (22 mu M), in the A2780 cells and even surpassing its activity in the cisplatin-resistant cells A2780cisR (2.4-8 mu M vs. 75.4; **P < 0.001). In the non-tumorigenic HEK cells poor selectivity toward cancer cells for most of the complexes was observed, as well as for cisplatin. (C) 2014 Elsevier Inc. All rights reserved.