Sustainable approach for synthesis of new coumarin-linked Schiff bases in DABCO-based ionic liquid and their identification as aldose reductase inhibitors

Abstract

Abstract Aldehyde reductase (ALR1) is the enzyme that speeds up the reduction of many types of aldehydes into sorbitol and D-glucose. The essential enzyme of the polyol pathway, aldose reductase (ALR2), is responsible for the development of chronic complications associated with diabetes when activated under hyperglycemic conditions. Since it is a crucial mediator for the oxidative and inflammatory signaling pathways, ALR is thought to be a target for various diseases. Many medicines are available for the treatment of ALR-associated issues but due to their long term side-effects they are not effectively used. Coumarin is a naturally occurring compound, and its derivatives are widely used in the treatment of many ailments. Therefore, in the pursuit to find potential alternate candidates as drug leads, we have prepared new coumarin-based Schiff base analogues using DABCO-C 7 -F ionic liquid and compared with conventional method. The sustainable approach making use of DABCO-C 7 -F ionic liquid, not only made the synthesis easier but also it is cost- and time-effective. The synthesized analogues were further examined for their potentials against ALR2 (IC50 = 1.61 to 11.20 µM) as well as checked selectivity via screening against ALR1 enzyme. Moreover, the molecular docking study was performed to elucidate the binding interactions of active compounds. The results showed that the synthesized compounds may have the potential to be further studied as new and selective anti-diabetic agents.