Design, synthesis, molecular modelling, ADME prediction and anti-hyperglycemic evaluation of new pyrazole-triazolopyrimidine hybrids as potent α-glucosidase inhibitors.

The aim of the present study is to design and synthesis of new pyrazole-triazolopyrimidine hybrids as potent α-glucosidase inhibitors. The target compounds 4a-n were synthesized by one-pot multicomponent approach with good yields and were characterized by various spectroscopic techniques and finally by single crystal X-ray diffraction method (4j). All the newly-synthesized derivatives have been screened for their α-glucosidase enzyme inhibition activity and acarbose taken as a standard drug. Among all the tested compounds, 4h has displayed excellent α-glucosidase enzyme inhibition activity with IC50 value 12.45 μM to the standard drug acarbose (IC50: 12.68 μM). Similarly, the compounds 4f and 4l have exhibited potent activity with IC50 values 14.47 μM and 17.27 μM respectively. Structure-activity relationship (SAR) studies of all the title compounds were established. The mode of binding interactions between the α-glucosidase enzyme and the compounds were studied. The drug-likeness properties (Lipinski parameters and in silico ADME properties) have predicted for the target compounds. The α-glucosidase inhibition, molecular docking and drug-likeness properties of the compounds 4h, 4f and 4l were suggested that these are promising hits for anti-diabetic activity.