Synthesis and potential vasorelaxant effect of a novel ruthenium-based nitro complex.

Autor: de Oliveira Neto J; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Coronel Nunes de Melo St., 1127, 60.430-275 Fortaleza, CE, Brazil; Drug Research and Development Center (NPDM), Federal University of Ceará, Coronel Nunes de Melo St., 1000, 60.430-275 Fortaleza, CE, Brazil., Marinho MM; State University of Ceará, Iguatu Faculty of Education, Science and Letters, Iguatu, CE, Brazil., Silveira JAM; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Coronel Nunes de Melo St., 1127, 60.430-275 Fortaleza, CE, Brazil; Drug Research and Development Center (NPDM), Federal University of Ceará, Coronel Nunes de Melo St., 1000, 60.430-275 Fortaleza, CE, Brazil. Electronic address: silveira.jam@gmail.com., Rocha DG; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Coronel Nunes de Melo St., 1127, 60.430-275 Fortaleza, CE, Brazil; Drug Research and Development Center (NPDM), Federal University of Ceará, Coronel Nunes de Melo St., 1000, 60.430-275 Fortaleza, CE, Brazil., Lima NCB; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Coronel Nunes de Melo St., 1127, 60.430-275 Fortaleza, CE, Brazil; Drug Research and Development Center (NPDM), Federal University of Ceará, Coronel Nunes de Melo St., 1000, 60.430-275 Fortaleza, CE, Brazil., Gouveia Júnior FS; Department of Organic and Inorganic Chemistry, Federal University of Ceará, 60455-760 Fortaleza, Brazil., Lopes LGF; Department of Organic and Inorganic Chemistry, Federal University of Ceará, 60455-760 Fortaleza, Brazil., de Sousa EHS; Department of Organic and Inorganic Chemistry, Federal University of Ceará, 60455-760 Fortaleza, Brazil., Martins AMC; Department of Clinical and Toxicological Analysis, School of Pharmacy, Federal University of Ceará, Fortaleza, CE, Brazil., Marinho AD; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Coronel Nunes de Melo St., 1127, 60.430-275 Fortaleza, CE, Brazil; Drug Research and Development Center (NPDM), Federal University of Ceará, Coronel Nunes de Melo St., 1000, 60.430-275 Fortaleza, CE, Brazil., Jorge RJB; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Coronel Nunes de Melo St., 1127, 60.430-275 Fortaleza, CE, Brazil; Drug Research and Development Center (NPDM), Federal University of Ceará, Coronel Nunes de Melo St., 1000, 60.430-275 Fortaleza, CE, Brazil., Monteiro HSA; Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Coronel Nunes de Melo St., 1127, 60.430-275 Fortaleza, CE, Brazil; Drug Research and Development Center (NPDM), Federal University of Ceará, Coronel Nunes de Melo St., 1000, 60.430-275 Fortaleza, CE, Brazil.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2022 Mar; Vol. 228, pp. 111666. Date of Electronic Publication: 2021 Nov 26.
DOI: 10.1016/j.jinorgbio.2021.111666
Abstrakt: This study aimed to investigate the synthesis and potential vasodilator effect of a novel ruthenium complex, cis-[Ru(bpy) 2 (2-MIM)(NO 2 )]PF 6 (bpy = 2,2'-bipyridine and 2-MIM = 2-methylimidazole) (FOR711A), containing an imidazole derivative via an in silico molecular docking model using β1 H-NOX (Heme-nitric oxide/oxygen binding) domain proteins of reduced and oxidized soluble guanylate cyclase (sGC). In addition, pharmacokinetic properties in the human organism were predicted through computational simulations and the potential for acute irritation of FOR711A was also investigated in vitro using the hen's egg chorioallantoic membrane (HET-CAM). FOR711A interacted with sites of the β1 H-NOX domain of reduced and oxidized sGC, demonstrating shorter bond distances to several residues and negative values of total energy. The predictive study revealed molar refractivity (RM): 127.65; Log Po/w = 1.29; topological polar surface area (TPSA): 86.26 Å 2 ; molar mass (MM) = 541.55 g/mol; low solubility, high unsaturation index, high gastrointestinal absorption; toxicity class 4; failure to cross the blood-brain barrier and to react with cytochrome P450 (CYP) enzymes CYP1A2, CYP2C19, CYP2C9, CYP2D6 and CYP3A4. After the HET-CAM assay, the FOR711A complex was classified as non-irritant (N.I.) and its vasodilator effect was confirmed through greater evidence of blood vessels after the administration and ending of the observation period of 5 min. These results suggest that FOR711A presented a potential stimulator/activator effect of sGC via NO/sGC/cGMP. However, results indicate it needs a vehicle for oral administration.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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