Trisubstituted thiophene analogues of 1-thiazolyl-2-pyrazoline, super oxidase inhibitors and free radical scavengers

• Published in: Bioorganic & medicinal chemistry 2013-01, Vol.21 (1), p.365-372
• Main Authors: Mandawad, Gajanan G., Dawane, Bhaskar S., Beedkar, Supriya D., Khobragade, Chandrahas N., Yemul, Omprakash S.
• Format: Article
• Language: English
• Subjects: Aging; allopurinol; Animals; Arteriosclerosis; atherosclerosis; Biphenyl Compounds - antagonists & inhibitors; Biphenyl Compounds - metabolism; Carcinogenesis; chalcones; chemistry; Free radical scavengers; Free Radical Scavengers - chemical synthesis; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacology; Free radicals; Gout; Green Chemistry Technology; Green synthesis; Hydrogen peroxide; Inflammation; metabolic diseases; Metabolic disorders; Molecular Docking Simulation; Molecular modelling; oxides; PEG-400; Picrates - antagonists & inhibitors; Picrates - metabolism; Polyethylene Glycols - chemistry; Rats; Rats, Wistar; Reactive oxygen species; Reactive Oxygen Species - antagonists & inhibitors; Reactive Oxygen Species - metabolism; Reperfusion; Solvents; Superoxide; superoxide anion; superoxide anions; Superoxide inhibitors; Superoxides - antagonists & inhibitors; Superoxides - metabolism; therapeutics; thiophene; Thiophenes - chemical synthesis; Thiophenes - chemistry; Thiophenes - pharmacology; Thiophenyl thiazolyl pyrazoline; Xanthine oxidase; Xanthine Oxidase - antagonists & inhibitors; Xanthine Oxidase - metabolism
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2012.09.060

Xanthine oxidase (XO) generates superoxide anions and H2O2 for the self-defence system of organism. Abnormal production of this superoxide’s (reactive oxygen species) is responsible for a number of complications including inflammation, metabolic disorder, cellular aging, reperfusion damage, atherosclerosis and carcinogenesis. Series of novel trisubstituted thiophenyl-1-thiazolyl-2-pyrazoline libraries are synthesized containing 2,5-dichloro thiophene, 5-chloro-2-(benzylthio) thiophene and 5-chlorothiophene-2-sulphonamide, from chalcones in PEG-400 as green solvent. Superoxide (XO) inhibitory and free radical scavenging activities were also figured out with molecular modeling analysis, bearing in mind their possible future for super oxide inhibitor (Gout) therapeutics, compound 3k shows interesting superoxide inhibitory and free radical scavenger activity with IC50=6.2μM, in comparison with allopurinol.