Desenvolvimento de complexos de Pd(II) e Pt(II) com ligantes N,N,O-doadores derivados do nitrofenol com aplicação anticâncer

Abstract

Cancer has emerged as a significant global concern, resulting in nearly 10 million deaths in 2020, according to IARC data. Chemotherapy involves the use of Pt(II) metallodrugs, such as cisplatin, which, despite being highly efficient, have undesirable side effects as well as intrinsic and acquired resistance. Since the implementation of cisplatin in cancer treatment, several metal ions, such as Pt(II) and Pd(II) have been used for the synthesis of new complexes with potential antineoplastic activity. In this sense, the present work consists on the preparation and structural characterization of four complexes, two of Pd(II), and two of Pt(II) containing the ligand 2-(methyl(2-(pyridin-2-yl)ethyl)amino )-4-nitrophenol (HL1) and chloride and thiocyanate coligands targeting promising metallodrugs to act as antitumor agents. The complexes [PdCl(L1)] (1), [PdSCN(L1)] (2), [PtCl(L1)] (3), and [PtSCN(L1)] (4) were characterized by elemental analysis, absorption in the infrared region, UV-visible spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopy, mass spectrometry and single-crystal X-ray diffraction. The results obtained from the characterization techniques confirmed the proposed structures in which the complexes have a square geometry, in which the metallic centers are coordinated via three sites by the N,N,O atoms of the HL1 ligand, with the fourth coordination site being occupied by a chlorine or sulfur atom of the thiocyanate ligand atom. Stability tests of the complexes were evaluated against different matrixes and the results showed that only complex 1 can keep its structure. The in vitro antiproliferative activity of Pd(II) and Pt(II) compounds was determined, and in some cases the activities observed were better than the free ligand. The data obtained also indicate different effects on the results of biological activity for the metal centers (Pd vs Pt), with complex 4 being the most active.