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

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

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  • NSTL
  • Elsevier
This study aimed to investigate the synthesis and potential vasodilator effect of a novel ruthenium complex, cis-[Ru(bpy)(2)(2-MIM)(NO2)]PF6 (bpy = 2,2'-bipyridine and 2-MIM = 2-methylimidazole) (FOR711A), containing an imidazole derivative via an in silico molecular docking model using beta 1 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 beta 1 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 angstrom(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.

Chemical characterizationRuthenium complexesIn silico modelingSoluble Guanylate CyclaseVasodilationChorioallantoic membraneSOLUBLE GUANYLATE-CYCLASEOCTANOL/WATER PARTITION-COEFFICIENTMEDICINAL CHEMISTRYDRUG DISCOVERYNO-DONOROXIDEPREDICTIONSOLUBILITYABSORPTIONBIOAVAILABILITY

de Sousa, Eduardo Henrique Silva、Martins, Alice Maria Costa、Marinho, Aline Diogo、Jorge, Roberta Jeane Bezerra、Monteiro, Helena Serra Azul、Silveira, Joao Alison de Moraes、Neto, Joselito de Oliveira、Marinho, Marcia Machado、Junior, Florencio Sousa Gouveia、Rocha, Danilo Galvao、Lima, Natalia Cavalcante Barbosa、de Franca Lopes, Luiz Gonzaga

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Univ Fed Ceara

Univ Estadual Ceara

2022

10.1016/j.jinorgbio.2021.111666

Journal of Inorganic Biochemistry

Journal of Inorganic Biochemistry

ISTP
ISSN：0162-0134
年,卷(期)：2022.228
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