1. Design and synthesis of pyridazinone-substituted benzenesulphonylurea derivatives as anti-hyperglycaemic agents and inhibitors of aldose reductase - an enzyme embroiled in diabetic complications.
- Author
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Yaseen R, Pushpalatha H, Reddy GB, Ismael A, Ahmed A, Dheyaa A, Ovais S, Rathore P, Samim M, Akthar M, Sharma K, Shafi S, Singh S, and Javed K
- Subjects
- Animals, Area Under Curve, Drug Design, Female, Male, Rats, Rats, Wistar, Spectrum Analysis methods, Sulfonylurea Compounds chemistry, Aldehyde Reductase antagonists & inhibitors, Diabetes Complications enzymology, Hypoglycemic Agents pharmacology, Lens, Crystalline enzymology, Pyridazines chemistry, Sulfonylurea Compounds pharmacology
- Abstract
Thirty new aryl-pyridazinone-substituted benzenesulphonylurea derivatives (I-XXX) were synthesized and evaluated for their anti-hyperglycaemic activity in glucose-fed hyperglycaemic normal rats. Twenty-three compounds (III-XI, XIV-XVII, XIX-XXIV, XXVI and XXVIII-XXX) showed more or comparable area under the curve (AUC) reduction percentage (ranging from 21.9% to 35.5%) as compared to the standard drug gliclazide (22.0%). On the basis of docking results, 18 compounds were screened for their in vitro ability to inhibit rat lens aldose reductase. Ten compounds (III-VI, XII, XVI-XVIII, XXI and XXVII) showed ARI activity with IC50 ranging from 34 to 242 μM. Out of these, two compounds IV and V showed best ARI activity which is comparable with that of quercetin. As a result, two compounds (IV and V) possessing significant dual action (anti-hyperglycaemic and aldose reductase inhibition) were identified and may be used as lead compounds for developing new drugs.
- Published
- 2016
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