Novos complexos bisbipiridínicos de rutênio(II) com potencial atividade farmacológica

Abstract

Coordination compounds, such as cisplatin and sodium nitroprusside, have demonstrated relevant pharmacological applications but are often associated with significant side effects. Ruthenium-based complexes have emerged as promising alternatives due to their lower systemic toxicity. In this work, six novel ruthenium (II) complexes were synthesized and characterized: FOR006, FOR0D6, FOR076, FOR086, cis-[Ru(bpy)₂(NO₂)CO]⁺, and WP1. Characterization techniques included NMR spectroscopy, UV-Vis absorption, FTIR, cyclic voltammetry, conductivity measurements, and elemental analysis. Single crystals suitable for X-ray diffraction were obtained for three of the complexes. Most compounds underwent photolysis upon UV or blue light irradiation, with controlled release of ligands such as NO, NO₂⁻, HNO, or CO. FOR086 and cis-[Ru(bpy)₂(NO₂)CO]⁺ also released NO/HNO under chemical or electrochemical reduction. In addition, FOR086 showed antioxidant activity through superoxide radical scavenging. All complexes tested exhibited low cytotoxicity in cardiomyocyte (H9c2) and murine macrophage (J774) cell lines (IC₅₀ > 100 µmol·L⁻¹), indicating good biocompatibility. Complexes containing the 6-ain ligand showed significant vasodilatory effects via distinct mechanisms: FOR006 and FOR0D6 likely act through direct activation of guanylate cyclase (GCs), while FOR076 and FOR086 function via NO release, activating the NO-GCs-cGMP signaling pathway. cis-[Ru(bpy)₂(NO₂)CO]⁺ also exhibited vasodilatory activity, although to a lesser extent. G-quadruplex DNA binding studies revealed that cis-[Ru(bpy)₂(NO₂)CO]⁺ effectively stabilizes these structures, particularly the one associated with the c-MYC oncogene, indicating potential anticancer properties. WP1 showed electrostatic interaction with DNA and promoted photospecific DNA cleavage through ligand release and the generation of reactive species, such as superoxide radicals. These findings highlight WP1 as a promising photosensitizer candidate for photochemotherapeutic applications.