Studies an the euglycemic and hypolipidemic potentials of the novel indoleanalogue of thiazolidinedione, DRF 2189

Euglycemic and hypolipidemic activities of a novel indole analogue of thiaz olidinedione, DRF 2189 (CAS 172647-53-9), have been evaluated in different animal models. Compared to troglitazone (CAS 97322-87-7), DRF 2189 exhibite d interesting plasma glucose and triglyceride lowering activity in genetica lly diabetic and obese db/db mice. It also produced a significant reduction in plasma glucose, triglyceride, total cholesterol levels and improvement in oral glucose tolerance in another genetic mouse model, the ob/ob mice. I n high-fat diet fed Sprague-Dawley rats, DRF 2189 treatment showed improvem ent in plasma lipid parameters. Like other thiazolidinediones, this compoun d also possesses peroxisome proliferator activated receptor gamma (PPAR gam ma) transactivation potential. In anaesthetized rat experiment, DRF 2189 pr oduced a transient fall in blood pressure without any change in the ECG pat tern. It showed non-specific smooth muscle relaxant activity against acetyl choline, histamine and potassium chloride induced contractions in isolated guinea pig ileum. A twenty-eight-day toxicity study in Wistar rats did not show any signs of treatment related adverse effects. The overall antidiabet ic and hypolipidemic activities of DRF 2189 are comparable with rosiglitazo ne (CAS 155141-29-0) and superior to troglitazone. In conclusion, results f rom these preclinical studies indicate that DRF 2189, a novel thiazolidined ione, has a marked potential for the management of type-2 diabetes.