Publication:
Elucidating the Structure-Activity relationships of the vasorelaxation and antioxidation properties of thionicotinic acid derivatives

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Issued Date

2010

Resource Type

Article

File Type

application/pdf

ISSN

14203049

DOI

10.3390/molecules15010198

Other identifier(s)

2-s2.0-75749143457

Rights Holder(s)

Scopus

Bibliographic Citation

Molecules. Vol 15, No.1 (2010), p.198-214

Suggested Citation

Prachayasittikul S., Wongsawatkul O., Worachartcheewan A., Nantasenamat C., Ruchirawat S., Prachayasittikul V. Elucidating the Structure-Activity relationships of the vasorelaxation and antioxidation properties of thionicotinic acid derivatives. Molecules. Vol 15, No.1 (2010), p.198-214. doi:10.3390/molecules15010198 Retrieved from: https://hdl.handle.net/20.500.14740/7662

Title

Elucidating the Structure-Activity relationships of the vasorelaxation and antioxidation properties of thionicotinic acid derivatives

Author(s)

Prachayasittikul S.
 Wongsawatkul O.
 Worachartcheewan A.
 Nantasenamat C.
 Ruchirawat S.
 Prachayasittikul V.

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.

Subject(s)

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

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URI

https://hdl.handle.net/20.500.14740/7662

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Scopus: Year 1983-2021

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