Synthesized 2-Substituted-3-Phenylthiazolidine-4-ones as Potent Antioxidants and Antidiabetic Agents
Purpose: To employ intramolecular cyclization of Schiff bases of pyrazole-4-carboxaldehydes to form thiazolidine-4-ones and determine the antioxidant and antidiabetic activity of the synthesized compounds.
Methods: The Schiff bases were obtained upon reaction between the electrophillic carbon atom of pyrazole-4-carboxaldehyde and the nucleophillic nitrogen atom of the amine. Preparation of thiazolidine-
4-one was preceded by attack of sulphur nucleophile of thioglycollic acid on imine carbon followed by intramolecular cyclization using acid catalyst. In vitro antioxidant activity was determined by 1, 1- diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay method using ascorbic acid as standard.
Evaluation of antidiabetic activity was carried out in streptazotocine-induced diabetes in Wister rats using rosiglitazone as reference drug. Blood glucose levels were estimated by GOD-POD kit. Serum biochemical parameters like total cholesterol, triglyceride, urea, creatinine and total protein level were
Results: Compounds 7a, 7b, 7c, 7e, 7j showed higher IC50 [Half maximal inhibitory concentration] values than the reference antioxidant, ascorbic acid. On the 21st day of treatment, there was significant fall and rise blood glucose level and body weight, respectively, compared to the anti-diabetic standard. There was decrease in serum cholesterol, triglyceride, creatinine and urea levels while high density lipoprotein (HDL) level and total protein levels increased after 21 days of treatment. Compared to rosiglitazone, compounds 7a, 7b, 7c, 7h, 7j showed stronger significant antidiabetic effect in hyperglycemic rats due, probably, to the presence of thiazolidine-4-one nucleus as well as parasubstitution on phenyl ring.
Conclusion: The 2-(3-Methyl-1H-pyrazol-4-yl)-3-phenylthiazolidin-4-ones possess potent antioxidant and antidiabetic activity but further studies are required to develop them for clinical use.
Keywords: Pyrazole-4-carboxaldehydes, Thiazolidine-4-one, Antioxidant, Anti diabetic