Please use this identifier to cite or link to this item: http://ir.swu.ac.th/jspui/handle/123456789/14758
Title: Elucidating the Structure-Activity relationships of the vasorelaxation and antioxidation properties of thionicotinic acid derivatives
Authors: Prachayasittikul S.
Wongsawatkul O.
Worachartcheewan A.
Nantasenamat C.
Ruchirawat S.
Prachayasittikul V.
Keywords: acetylcholine
antioxidant
drug derivative
n(g) nitroarginine methyl ester
nicotinamide
nicotinic acid
prostaglandin synthase inhibitor
thiol derivative
thionicotinamide
animal
article
chemical structure
chemistry
cytology
drug effect
endothelium cell
in vitro study
male
physiology
rat
Sprague Dawley rat
structure activity relation
thoracic aorta
vasodilatation
Acetylcholine
Animals
Antioxidants
Aorta, Thoracic
Cyclooxygenase Inhibitors
Endothelial Cells
Male
Models, Molecular
NG-Nitroarginine Methyl Ester
Niacin
Niacinamide
Rats
Rats, Sprague-Dawley
Structure-Activity Relationship
Sulfhydryl Compounds
Vasodilation
Issue Date: 2010
Abstract: Nicotinic acid, known as vitamin B3, is an effective lipid lowering drug and intense cutaneous vasodilator. This study reports the effect of 2-(1-adamantylthio)nicotinic acid (6) and its amide 7 and nitrile analog 8 on phenylephrine-induced contraction of rat thoracic aorta as well as antioxidative activity. It was found that the tested thionicotinic acid analogs 6-8 exerted maximal vasorelaxation in a dose-dependent manner, but their effects were less than acetylcholine (ACh)-induced nitric oxide (NO) vasorelaxation. The vasorelaxations were reduced, apparently, in both NG-nitro-L- arginine methyl ester (L-NAME) and indomethacin (INDO). Synergistic effects were observed in the presence of L-NAME plus INDO, leading to loss of vasorelaxation of both the ACh and the tested nicotinic acids. Complete loss of the vasorelaxation was noted under removal of endothelial cells. This infers that the vasorelaxations are mediated partially by endothelium-induced NO and prostacyclin. The thionicotinic acid analogs all exhibited antioxidant properties in both 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide dismutase (SOD) assays. Significantly, the thionicotinic acid 6 is the most potent vasorelaxant with ED50 of 21.3 nM and is the most potent antioxidant (as discerned from DPPH assay). Molecular modeling was also used to provide mechanistic insights into the vasorelaxant and antioxidative activities. The findings reveal that the thionicotinic acid analogs are a novel class of vasorelaxant and antioxidant compounds which have potential to be further developed as promising therapeutics.
URI: https://www.scopus.com/inward/record.uri?eid=2-s2.0-75749143457&doi=10.3390%2fmolecules15010198&partnerID=40&md5=6d9a6785dcd53c8b8e4521e2c31921f6
http://ir.swu.ac.th/jspui/handle/123456789/14758
ISSN: 14203049
Appears in Collections:SCOPUS 1983-2021

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