Long-chain fatty dihydropyridines: Docking calcium channel studies and antihypertensive activity.

Autor: Santa-Helena E; Postgraduate Program in Physiological Sciences, Institute of Biological Sciences, Federal University of Rio Grande - FURG, Rio Grande, RS, Brazil; Institute of Biological Sciences, Federal University of Rio Grande - FURG, Rio Grande, RS, Brazil., Cabrera DDC; Kolbe Organic Synthesis Laboratory, School of Chemistry and Food, FURG, Rio Grande, RS., D'Oca MGM; Kolbe Organic Synthesis Laboratory, School of Chemistry and Food, FURG, Rio Grande, RS., Scaini JLR; Computational Biology Laboratory, Computational Sciences Center, FURG, Rio Grande, RS., de Oliveira MWB; Computational Biology Laboratory, Computational Sciences Center, FURG, Rio Grande, RS., Werhli AV; Computational Biology Laboratory, Computational Sciences Center, FURG, Rio Grande, RS., Machado KDS; Computational Biology Laboratory, Computational Sciences Center, FURG, Rio Grande, RS., Gonçalves CAN; Postgraduate Program in Physiological Sciences, Institute of Biological Sciences, Federal University of Rio Grande - FURG, Rio Grande, RS, Brazil; Institute of Biological Sciences, Federal University of Rio Grande - FURG, Rio Grande, RS, Brazil., Nery LEM; Postgraduate Program in Physiological Sciences, Institute of Biological Sciences, Federal University of Rio Grande - FURG, Rio Grande, RS, Brazil; Institute of Biological Sciences, Federal University of Rio Grande - FURG, Rio Grande, RS, Brazil. Electronic address: luiznery@furg.br.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2020 Oct 15; Vol. 259, pp. 118210. Date of Electronic Publication: 2020 Aug 05.
DOI: 10.1016/j.lfs.2020.118210
Abstrakt: Aims: From the synthesis of 43 lipophilic dihydropyridines, the aim of this study was to verify whether the new dihydropyridines have calcium channel affinity using coupling studies and to determine antihypertensive and antioxidant properties, as well as toxicology and toxicity nifedipine and three new compounds, were chosen from the previous results.
Materials and Methods: The animals were treated for 56 days, 28 days with N (ω) -nitro-L-arginine methyl ester to induce hypertension, and then treated for another 28 days with the new di- hydropyridine and the standard drug nifedipine. Throughout the treatment the animals had their blood pressure measured and their heart rate checked by pletysmography. After treatment the animals were euthanised, blood samples were collected for creatine kinase and urea analysis, and the brain, heart and liver were collected for oxidative status analysis (quantification of reactive oxygen species, total antioxidant capacity, and lipid peroxidation).
Key Findings: Compounds 2c, and 9a, and nifedipine significantly reduced blood pressure to control group levels. The tachycardia caused by the induction of hypertension was reversed by 2c and 9a compounds. Regarding oxidative stress analyzes, the compounds that had the best performances were also 2c and 9a. Overall the results demonstrate that two of the three new dihydropyridines tested demonstrated performance equal to or superior to the standard drug nifedipine.
Significance: In this study, for the first time, docking was applied to analyse 43 fatty dihydropyridines regarding their calcium channel binding. Afterwards, three fatty dihydropyridines were chosen and their antihypertensive and antioxidant properties.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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