New nitrosyl ruthenium complexes with combined activities for multiple cardiovascular disorders.
Florêncio Sousa Gouveia JúniorJoão Alison de Moraes SilveiraThais Muratori HolandaAline Diogo MarinhoLisa A RidnourDavid A WinkRodrigo José Bezerra de SiqueiraHelena Serra Azul MonteiroEduardo Henrique Silva de SousaLuiz Gonzaga de França LopesPublished in: Dalton transactions (Cambridge, England : 2003) (2023)
Nitrosyl ruthenium complexes are promising platforms for nitric oxide (NO) and nitroxyl (HNO) release, which exert their therapeutic application. In this context, we developed two polypyridinic compounds with the general formula cis -[Ru(NO)(bpy) 2 (L)] n + , where L is an imidazole derivative. These species were characterized by spectroscopic and electrochemical techniques, including XANES/EXAFS experiments, and further supported by DFT calculations. Interestingly, assays using selective probes evidenced that both complexes can release HNO on reaction with thiols. This finding was biologically validated by HIF-1α detection. The latter protein is related to angiogenesis and inflammation processes under hypoxic conditions, which is selectively destabilized by nitroxyl. These metal complexes also presented vasodilating properties using isolated rat aorta rings and demonstrated antioxidant properties in free radical scavenging experiments. Based on these results, the new nitrosyl ruthenium compounds showed promising characteristics as potential therapeutic agents for the treatment of cardiovascular conditions such as atherosclerosis, deserving further investigation.
Keyphrases
- nitric oxide
- oxidative stress
- density functional theory
- molecular docking
- endothelial cells
- cardiovascular disease
- type diabetes
- gold nanoparticles
- ionic liquid
- small molecule
- label free
- molecular dynamics simulations
- vascular endothelial growth factor
- hydrogen peroxide
- high throughput
- human milk
- aortic valve
- binding protein
- living cells
- replacement therapy
- anti inflammatory
- mass spectrometry
- high resolution