Síntese de complexos de platina(II) com ligantes lipofílicos derivados de 1,3,4-oxadiazol e piperazina e seus estudos biológicos

Abstract

The cisplatin was the first inorganic compound used as an antitumoral drug, but its side effects and resistance mechanism drove the search for more active and less toxic analog complexes. The ligands have important role in design of a new complex. They can modulate the lipophilicity, lability, steric effect and can contribute synergistically. Derivatives from piperazine and 1,3,4-oxadiazole have several biological activities like anticancer, antiparasitic, antifungal, antibacterial, antidepressant, antituberculosis, anti-inflammatory and anti-HIV activities. In the present work three platinum complexes were synthesized with ligands that piperazine and 1,3,4-oxadiazole derivatives. Ligands and complexes differ from each other by piperazine alkylation with 8, 10 or 12 carbons resulting in a variation of lipophilicity. The synthesized complexes were analyzed by infrared vibrational spectroscopy, Raman vibrational spectroscopy, ultraviolet-visible electronic absorption spectroscopy, 1H, 13C and 195Pt nuclear magnetic resonance spectroscopy, thermogravimetric analysis, mass spectrometry, molar conductivity and elemental analysis. The biological studies were perfomed through analysis of inhibitory concentration of 50% of cell viability, IC50, in tumor cells B16-F1, CT26-WT and non-tumor cells, BHK-21, and interaction studies with biomolecules like BSA and DNA. Through the results obtained it was possible to conclude that in the three synthesized complexes the ligand are monodentate and coordinated to metal by sulfur atom from the oxadiazole moiety. They are negativelly charged and neutralized by K+ counter ion. The interaction of the complexes with the biomolecules BSA and DNA can be influenced by the alkyl side chain. The complexes are less cytotoxic than their respectives ligands and, both in complexes and ligands, those that have larger alkyl chain had lowest values of IC50 (more cytotoxics), allowing us to establish the relationship betwen activity and lipophilicity.