title: Antihyperuricemic effects of thiadiazolopyrimidin-5-one analogues in oxonate treated rats.
abstract: Hyperuricemia is a risk factor for not only gout, but also to a variety of disorders that affect the vital organ systems of the human body. The xanthine oxidase (XO) is the key enzyme in the production of uric acid and its inhibition can inhibit hyperuricemia. Although, XO inhibitor allopurinol is widely prescribed antigout agent but its use is not without any side effects. Previously, we described the synthesis of four novel thiadiazolopyrimidin-5-one analogues as effective XO inhibitors and molecular docking studies also confirmed this. When these analogues were tested in potassium oxonate treated rats, their serum uric acid and creatinine levels were dropped significantly from 4.85±0.03 mg/dl to 1.21±0.01 mg/dl and 0.92±0.02 mg/dl to 0.40±0.02 mg/dl respectively. Among the pyrimidine analogues tested, 6a was most potent. Histological examinations of both liver and kidney tissues exhibited severe necrosis in oxonate treated rats and pyrimidine analogues could significantly attenuate this with a correlative inhibitory profile of hepatic XO from the same rats. Our results demonstrate antihyperuricemic effect of novel thiadiazolopyrimidin-5-one analogues in oxonate treated rats, which can be further explored not only as antigout therapeutics but also in other systems where hyperuricemia is the driving cause of the disease.
authors.affiliation: Department of Studies in Microbiology, University of Mysore, Manasagangotri, Mysore 570006, India; Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570006, India.
authors.forename: Kadanuru R
authors.initials: KR
authors.lastname: Sathisha
authors.affiliation: Department of Studies in Microbiology, University of Mysore, Manasagangotri, Mysore 570006, India. Electronic address: sguom@yahoo.com.
authors.forename: Shubha
authors.initials: S
authors.lastname: Gopal
authors.affiliation: Department of Studies in Chemistry, University of Mysore, Manasagangotri, Mysore 570006, India. Electronic address: rangappaks@gmail.com.
authors.forename: Kanchugarakoppal S
authors.initials: KS
authors.lastname: Rangappa
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D003404:Creatinine / Q000097:blood; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D033461:Hyperuricemia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D062105:Molecular Docking Simulation; D010094:Oxonic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013830:Thiadiazoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D014527:Uric Acid / Q000097:blood; D014969:Xanthine Oxidase / Q000737:chemistry / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D013830:Thiadiazoles; D014527:Uric Acid; D010094:Oxonic Acid; D003404:Creatinine; D014969:Xanthine Oxidase
keywords: Gout; Hyperuricemia; Potassium oxonate; Thiadiazolopyrimidin-5-one analogues; Xanthine oxidase