Síntese, caracterização e estudos biológicos de complexos de platina(II) contendo hidrazidas e carbazatos

Abstract

This work describes the synthesis, characterization and biological evaluation of novel platinum(II) complexes of type cis-[Pt(L)2X2], where X = Cl or I and L = 4- methoxybenzylcarbazate (4-MC), benzyl carbazate (BC), 4-fluorophenoxyacetic acid hydrazide (4-FH), 3-methoxybenzyl hydrazide (3-MC), ethyl carbazate (EC), tert-butyl carbazate (TC) or 4-hydroxyphenoxyacetic acid hydrazide (4-HH). The complexes were synthesized by the slow addition of the ligand to an aqueous solution of K2[PtCl4] or K2[PtI4]. After 24 hours the resulting compounds were isolated by simple filtration and characterized by elemental analysis, conductivity measurements, infrared spectroscopy (IR), high-resolution electrospray ionization mass spectrometry (HRESIMS) and nuclear magnetic resonance (NMR). The structures of the platinum(II) complexes were optimized and theoretical data show good agreement with the experimental results, suggesting that in all reactions, the metallic ion coordinates to two hydrazides or carbazates via NH2 groups. The cytotoxic activity of three representative compounds was evaluated in a chronic myelogenous leukemia cell line. The platinum complex with 4-fluorophenoxyacetic acid hydrazide was more active than free ligand and carboplatin, with IC50 = 7.0 μmol L 1, thus can be considered a promising antitumor agent. In addition, the platinum complexes with 4-methoxybenzylcarbazate (4-MC) and benzyl carbazate (BC) exhibited good activity. However, microbiological testing against Mycobacterium tuberculosis showed that all complexes and organic ligands are not active.