An efficient Nano-Copper catalyzed base-free Knoevenagel condensation: A facile synthesis, molecular modelling simulations, SAR and hypoglycemic studies of new quinoline tethered acridine analogues as PPARγ agonists

Abstract

In the present investigation new series of quinoline substituted acridine analogues were synthesized through Knoevenagel condensation of acridine with various 2,4-dichlorothiazole-5-carbaldehyde derivatives. Shorter reaction time, simple work-up procedure, clean reaction profiles and reusability of the catalyst up to five cycles are some of the noteworthy highlights of the reported protocol. The synthesized compounds were successfully characterized by using 1H NMR,13C NMR and HRMS. Molecular docking simulations were carried out to decipher the binding nature of the synthesized derivatives towards PPARγ protein. The results obtained from docking analysis showed that the synthesized derivatives possess good binding interaction towards PPARγ protein. Interestingly in-vitro testing of the compounds for hypoglycemic activity evaluation through α-amylase and α-glucosidase enzyme inhibition assays reveals that the compounds 3d and 3f possess good hypoglycemic efficacy comparable to standards pioglitazone and acarbose.