New arylidene-linked chromane-2,4-dione analogs as potential leads for diabetic management; syntheses, α-amylase inhibitory, and radical scavenging activities

A range of substituted arylidene chromane-2,4-dione derivatives 1–30 were synthesized by the condensation reaction between 6-chloro-4-hydroxycoumarin and different benzaldehydes in ethanol. All synthesized derivatives are structurally new and fully characterized by various spectroscopic approaches. Compounds were tested for α-amylase inhibitory and radical (DPPH and ABTS) scavenging activities in vitro. When compared to the standard acarbose (IC 50 = 12.9 ± 0.1 µM), all derivatives showed significant inhibitory activity against the α-amylase enzyme, with IC 50 values ranging from 7.7 ± 0.1 to 60.7 ± 0.1 µM. Compounds were also found to be good radical scavengers of DPPH (IC 50 = 21.6 ± 0.2 to 92.1 ± 0.1 µM) and ABTS (IC 50 = 22.4 ± 0.1 to 92.7 ± 0.1 µM), compared to standard ascorbic acid (DPPH, IC 50 = 14.4 ± 0.1; ABTS, IC 50 = 14.9 ± 0.1 µM). Kinetic studies performed on most active molecules revealed competitive-type inhibition mechanisms. The structure–activity relationship (SAR) has been studied to determine the effect of different substitutions of compounds on inhibitory potential. Docking studies of these synthesized coumarin derivatives revealed significant binding interactions with the α-amylase enzyme's catalytic site.