IN-VIVO ANTIDIABETIC EVALUATION OF QUINOLINE–1,3,4 THIADIAZOLE HYBRIDS IN ALLOXAN-INDUCED DIABETIC RATS

Abstract

Diabetes mellitus is a chronic metabolic condition associated with severe microvascular and macrovascular complications and characterised by chronic hyperglycemia. Although several antidiabetic drugs are available, the search for safer and more effective treatment choices is a serious challenge. In the present investigation, alloxan-induced diabetic rat model was utilised to examine the in vivo antihyperglycemic potential of newly synthesised quinoline–1,3,4-thiadiazole hybrids. Alloxan monohydrate (150 mg/kg) was injected intraperitoneally into Wistar rats to induce experimental diabetes. Diabetic rats with fasting blood glucose levels > 200 mg/dL were chosen at random to receive vehicle, test compounds (5 mg/kg, p.o.) or glibenclamide (5 mg/kg, p.o.) for fourteen days in a row. Fasting blood glucose was tested on days 0, 3, 7 and 14. Persistent hyperglycemia was observed in the diabetic control group due to alloxan administration while therapy with the quinoline-1,3,4-thiadiazole hybrids resulted in a significant reduction of fasting blood glucose in a time-dependent manner. After 14 days of treatment, compound 5e demonstrated the highest antihyperglycemic activity among the studied derivatives, reducing the fasting blood glucose from 264.8 ± 2.58 mg/dL to 117.0 ± 1.58 mg/dL. Its impact was comparable to conventional drug glibenclamide (107.4 ± 4.82 mg/dL). Compounds 5h and 5i also produced significant glucose lowering effects although to a lesser extent than 5e. The results indicated that 5e could be a lead contender and quinoline 1,3,4-thiadiazole hybrids have a promising in vivo antihyperglycemic activity.