Experimental and Computational Interaction Studies of (E)-N'-Benzylidene-5-Methyl-1H-Pyrazole-3-Carbohydrazide with α-Glucosidase and α-Amylase Enzymes: A Detailed Structural, Spectroscopic, and Biophysical Study

• Published in: Polycyclic aromatic compounds Vol. 43; no. 2; pp. 1812 - 1832
• Main Authors: Karrouchi, Khalid, Fettach, Saad, Tamer, Ömer, Avcı, Davut, Başoğlu, Adil, Atalay, Yusuf, Radi, Smaail, Ghabbour, Hazem A., Mabkhot, Yahia N., Faouzi, My El Abbes, Ansar, M'hammed
• Format: Journal Article
• Language: English
• Published: Philadelphia Taylor & Francis 07.02.2023; Taylor & Francis Ltd
• Subjects: Amylases; Chemical synthesis; Computer applications; crystal structure; Density functional theory; DFT; Enzymes; Glucosidase; Inhibitors; Mathematical analysis; Molecular docking; Molecular orbitals; Molecular structure; NMR; Nuclear magnetic resonance; Pyrazole; Pyrazoles; Single crystals; X-ray diffraction; α-Amylase; α-Glucosidase; α-glucosidase and α-amylase
• ISSN: 1040-6638; 1563-5333
• DOI: 10.1080/10406638.2022.2036774

Herein we report the synthesis, DFT calculations, and molecular docking studies of a pyrazole derivative, (E)-N'-benzylidene-5-methyl-1H-pyrazole-3-carbohydrazide (E-BMPC) as α-glucosidase and α-amylase inhibitor. Molecular structure of E-BMPC has been confirmed by single crystal X-ray diffraction (XRD), FTIR, 1 H, and 13 C NMR spectra. In addition, density functional theory (DFT) calculations on E-BMPC were carried out to obtain frontier molecular orbital energies and first-order static hyperpolarizability (β). The α-amylase and α-glucosidase enzyme inhibitory of E-BMPC was also tested. E-BMPC displayed moderate inhibitory activity with IC 50 values 310.57 ± 2.67 and 182.19 ± 3.20 against α-glucosidase and α-amylase enzymes, respectively. Molecular docking analysis provided the inhibition constant of E-BMPC molecule for α-amylase enzyme as 33.60 µM. Both in vitro and in silico enzyme inhibition studies showed that E-BMPC molecule is a better inhibitor for α-amylase than α-glucosidase. The β parameter for the molecule under investigation was also calculated as 4.2 × 10 −30  esu.