Aldose reductase, a key enzyme of a polyol pathway, catalyses NADPH-dependent reduction of glucose to sorbitol. Increased activity of this enzyme is considered as a major factor contributing to the development of diabetic complications; therefore, aldose reductase enzyme serves as an important target for inhibitors useful in diabetic complication treatment. In this work, a database of sesquiterpenes was prepared and screened for a drug like properties. The screening was carried out using theLipinskis rule. The co-crystallised structure of aldose reductase was obtained from Protein Data bank and prepared for docking. Docking study was performed using 198 sesquiterpene lactones that passed screening, and compounds with the lowest binding energy and favourable binding interactions were selected. Six of the best ranking compounds selected have binding energy ranging from 11.96 Kcal/mol to -9.45 Kcal/mol, which is comparable to that of the standard inhibitor Idd594. They also show good complementarity in their binding to the residues of the binding pocket. The results suggest that the selected sesquiterpene lactones offered a potential inhibitory activity towards aldose reductase enzyme and may serve as a potential lead for further validation in ameliorating diabetic complications.
Key words: Sesquiterpene lactones, Aldose reductase, Binding energy, docking, Autodock
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