2-(allylthio)-5-(5-phenyl-1H-pyrazol-3-yl)-1,3,4-oxadiazole: Synthesis, single crystal XRD, spectroscopic characterization, antidiabetic activity, DFT and ADMET studies

Abstract

Here, we synthesized a new potent antidiabetic agent of pyrazolyl-1,3,4-oxadiazole derivative, named 2-(allylthio)-5-(5-phenyl-1H-pyrazol-3-yl)-1,3,4-oxadiazole (ATPO) and characterized it by FT-IR, UV–vis, 1H NMR, 13C NMR, HRMS-ESI, X-ray crystal structure and evaluated as dual inhibitor for α-amylase and α-glucosidase enzymes. Predicted FT-IR, UV–vis, 1H NMR, 13C NMR and UV–vis spectra and geometrical parameters for the optimized structures of ATPO in gas phase and ethanol solution by using B3LYP/6–311++G(d,p) method evidenced very good concordances with the corresponding experimental ones. Studies on atomic charges, molecular electrostatic potentials, stabilization energies and topological properties show that the phenyl, pyrazole and oxadiazole rings together with the allyl thiol moiety play a very important role in the stability, reactivity and behaviours of ATPO in both media. Thus, the compound is less stable in solution probably due to its higher reactivity in this medium and to its solvation energy (-75.89 kJ/mol). Complete vibrational assignments and the scaled force constants were performed for ATPO in both media. Also, ATPO exhibited outstanding α-glucosidase as well as α-amylase inhibitory potential with IC50 values of 35.47 ± 0.42 and 68.99 ± 1.08 µM, respectively, as compared to reference drug acarbose (IC50 (α-glucosidase) = 72.58 ± 0.68 µM, IC50 (α-amylase) = 115.6 ± 0.59 µM). In addition, ADMET studies were performed to investigate the possibility of using of the title compound as antidiabetic drug.