synthesis and characterization of novel pyrazoline derivatives as dual α-amylase /α-glucosidase inhibitors: molecular modeling and kinetic study

Different series of novel tri-substituted pyrazoline derivatives were designed, synthesized, and evaluated for their inhibitory effect against α-glucosidase and α-amylase. All the evaluated compounds showed fluctuating effects against both α-glucosidase and α-amylase with IC50= 170.7 ± 5.24 to 2704.0 ± 2.32 uM and 60.37 ± 3.55 to 353.70 ± 3.95 uM as compared to standard acarbose (IC50 = 558.0 ± 6.83 uM) and (IC50 = 90.54 ± 5.11 uM), respectively. Obviously, compound 10 presented the strongest inhibitory activities among all evaluated com-pounds. It showed approximately 3-fold and 1.5-fold more potent against α-glucosidase and α-amylase, respectively, than standard. Interestingly, kinetic studies were performed for compound 10 to determine the target inhibiting mode. Furthermore, molecular modeling and ADME properties were also scrutinized to predict the binding mode of compound 10 and prove its stability in the enzymes binding pockets