Diversely functionalized benzopyran scaffolds as potential lead candidates for treating Alzheimer's disease and diabetes

Abstract

The current study deals with the preparation of polyfunctional benzopyran derivatives 1–25, synthesized by the condensation of 2,4-dihydroxy benzophenone, substituted aldehydes, and malononitrile. These compounds were evaluated for their inhibitory potential against AChE, BChE, α-amylase, and α-glucosidase enzymes, as well as for DPPH radical scavenging activity. Among 25 compounds, 1, 4–6, 14, 15, and 25 showed excellent inhibition against AChE (IC50 = 5.30 - 37.14 µM) and BChE (IC50 = 8.20 - 43.13 µM), compared to standard donepezil (IC50 = 40.05 for AChE; 45.00 µM for BChE), respectively. Moreover, compounds 2, 3, 11, and 12 inhibited α-amylase (IC50 = 1.88 - 11.42 µM) and α-glucosidase (IC50 = 2.54 - 8.36 µM) with greater potency than the standard acarbose (IC50 = 14.65 µM). Kinetic studies of the active compounds were also carried out to find the mode of inhibition. Furthermore, molecular docking was performed to determine the ligands' interaction with the enzyme's active site. In addition, compounds 9, 19, and 21 exhibited significant DPPH radical scavenging activity (SC50 = 44.88 - 64.61 µM) compared to BHT (SC50 = 66.34 µM). Thus, this study suggests that the reported compounds hold the potential to be further advanced as lead anti-Alzheimer and anti-diabetic agents.