Design, Synthesis, and Biological Evaluation of Thiazolidine‐2, 4‐dione Conjugates as PPAR‐γ Agonists. Issue 6 (21st April 2015)

• Record Type: Journal Article
• Authors: Nazreen, Syed; Alam, Mohammad Sarwar; Hamid, Hinna; Yar, Mohammad Shahar; Dhulap, Abhijeet; Alam, Perwez; Pasha, Mohammad Abdul Qadar; Bano, Sameena; Alam, Mohammad Mahboob; Haider, Saqlain; Kharbanda, Chetna; Ali, Yakub; Pillai, Kolakappi
• Is Part Of: Archiv der Pharmazie. Volume 348:Issue 6(2015:Jun.)
• Page Start: 421
• Page End: 432
• Publication Date: 2015-04-21
• Subjects: Pharmaceutical chemistry -- Periodicals; Pharmacology -- Periodicals; 615.19
• DOI: 10.1002/ardp.201400280
• Languages: English
• ISSNs: 0365-6233

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ardp201400280-sec-0001" sec-type="section"> <p>A library of synthesized conjugates of phenoxy acetic acid and thiazolidinedione <bold>5a</bold>–<bold>m</bold> showed potent peroxisome proliferator activated receptor‐γ (PPAR‐γ) transactivation as well as significant blood glucose lowering effect comparable to the standard drugs pioglitazone and rosiglitazone. Most of the compounds showed higher docking scores than the standard drug rosiglitazone in the molecular docking study. Compounds <bold>5l</bold> and <bold>5m</bold> exhibited PPAR‐γ transactivation of 54.21 and 55.41%, respectively, in comparison to the standard drugs pioglitazone and rosiglitazone, which showed 65.94 and 82.21% activation, respectively. Compounds <bold>5l</bold> and <bold>5m</bold> significantly lowered the blood glucose level of STZ‐induced diabetic rats. Compounds <bold>5l</bold> and <bold>5m</bold> lowered the AST, ALT, and ALP levels more than the standard drug pioglitazone. PPAR‐γ gene expression was significantly increased by compound <bold>5m</bold> (2.00‐fold) in comparison to the standard drugs pioglitazone (1.5‐fold) and rosiglitazone (1.0‐fold). Compounds <bold>5l</bold> and <bold>5m</bold> did not cause any damage to the liver and could be considered as promising candidates for the development of new antidiabetic agents.</p> </sec> </abstract>