Antioxidant activity of an aminothiazole compound: possible mechanisms.
Oceans are among the richest natural sources of many bioactive compounds. Several of these compounds have shown pharmacological activities for many diseases. Dendrodoine (5-[(3-N-dimethylamino)-1,2,4-thiadiazolyl]-3-indanyl methanone) is an alkaloid extracted from the marine tunicate Dendrodoa grossularia. Aminothiazoles have a wide range of biological activities including anti-tumor and antioxidant properties. The aim of our study was to examine the antioxidant ability of an aminothiazole derivative, dendrodoine analogue (DA) [(4-amino-5-benzoyl-2-(4-methoxy phenylamino) thiazole] which has been chemically synthesized and is similar to dendrodoine. In all the biochemical assays used in our study, corresponding to different levels of protection, DA showed concentration dependent antioxidant ability. DA (3.07 microM) showed an ability to inhibit 2,2'-azobis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) radical formation to the extent of 0.17 microM of 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). The ferric complex reducing ability of 3.07 microM DA was equivalent to 110 microM Trolox. 3.07 microM DA gave 84% protection against deoxyribose degradation, a measure of hydroxyl radical scavenging. DA also has an ability to scavenge NO radical, 3.07 microM DA effecting 20% scavenging. Concentration dependent inhibition of lipid peroxidation and protein oxidation induced by 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) and ascorbate-Fe2+ was observed with low concentrations of DA (1.5-3.07 microM). Mechanistic studies using pulse radiolysis revealed that DA scavenges peroxyl radicals with a bimolecular rate constant of 3 x 10(8)M(-1)s(-1). Moreover, the initially formed nitrogen-centered radical gets transformed into sulfur-centered radical before furnishing any final product. Our results indicated that DA can be a free radical scavenger and potential antioxidant for future application.
De
Strayo
S
Radiation Biology and Health Sciences, Bhabha Atomic Research Centre, Mumbai-400085, India.
Adhikari
S
S
Tilak-Jain
J
J
Menon
V P
VP
Devasagayam
T P A
TP
D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D004249:DNA Damage; D005260:Female; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008930:Mitochondria, Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D010084:Oxidation-Reduction / Q000187:drug effects; D011506:Proteins / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology*
C496402:4-amino-5-benzoyl-2-(4-methoxyphenylamino)thiazole; D000975:Antioxidants; D016166:Free Radical Scavengers; D011506:Proteins; D013844:Thiazoles; D014230:Triazoles; C004483:2-aminothiazole; D004247:DNA