New nitrosyl ruthenium complexes with combined activities for multiple cardiovascular disorders.

Autor:	Gouveia Júnior FS; Laboratory of Bioinorganic Chemistry, Department of Organic and Inorganic Chemistry, Federal University of Ceara, 60455-760, Fortaleza-CE, Brazil. eduardohss@dqoi.ufc.br., Silveira JAM; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceara, Coronel Nunes de Melo St., 1127, 60.430-275, Fortaleza-CE, Brazil.; Drug Research and Development Center (NPDM), Federal University of Ceara, Coronel Nunes de Melo St., 1000, 60.430-275, Fortaleza-CE, Brazil., Holanda TM; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceara, Coronel Nunes de Melo St., 1127, 60.430-275, Fortaleza-CE, Brazil.; Drug Research and Development Center (NPDM), Federal University of Ceara, Coronel Nunes de Melo St., 1000, 60.430-275, Fortaleza-CE, Brazil., Marinho AD; Drug Research and Development Center (NPDM), Federal University of Ceara, Coronel Nunes de Melo St., 1000, 60.430-275, Fortaleza-CE, Brazil., Ridnour LA; National Cancer Institute, Cancer and Inflammation Program, Frederick, Maryland 21702, USA., Wink DA; National Cancer Institute, Cancer and Inflammation Program, Frederick, Maryland 21702, USA., de Siqueira RJB; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceara, Coronel Nunes de Melo St., 1127, 60.430-275, Fortaleza-CE, Brazil., Monteiro HSA; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceara, Coronel Nunes de Melo St., 1127, 60.430-275, Fortaleza-CE, Brazil.; Drug Research and Development Center (NPDM), Federal University of Ceara, Coronel Nunes de Melo St., 1000, 60.430-275, Fortaleza-CE, Brazil., Sousa EHS; Laboratory of Bioinorganic Chemistry, Department of Organic and Inorganic Chemistry, Federal University of Ceara, 60455-760, Fortaleza-CE, Brazil. eduardohss@dqoi.ufc.br., Lopes LGF; Laboratory of Bioinorganic Chemistry, Department of Organic and Inorganic Chemistry, Federal University of Ceara, 60455-760, Fortaleza-CE, Brazil. eduardohss@dqoi.ufc.br.
Jazyk:	angličtina
Zdroj:	Dalton transactions (Cambridge, England : 2003) [Dalton Trans] 2023 Apr 25; Vol. 52 (16), pp. 5176-5191. Date of Electronic Publication: 2023 Apr 25.
DOI:	10.1039/d3dt00059a
Abstrakt:	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.
Databáze:	MEDLINE
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