Synthesis, Crystal Structure, Hirshfeld Surface Analysis, DFT and Antihyperglycemic Activity of 9-Allyl

Abstract

In this work, a novel benzodiazepine-2-one derivative (4) was synthesized by N-allylation of cyclopenta[e][1,5]benzodiazepine-2-one. The chemical structure of the target compound was confirmed by FT-IR, UV-Vis, (1) H & C-13-NMR, GC-MS and single-crystal X-ray diffraction methods. Structural, topolog-ical, electronic and reactivity of new molecule were studied by using B3LYP/6-311 ++ G ** calculations in ethanol and in gas phase. Studies on charges, molecular electrostatic potentials, atoms in molecules (AIM), natural bond orbital (NBO), and frontier orbitals have evidenced that the seven membered diazepine ring play a very important role in the properties of (4) increasing its reactivity in ethanol. Good concordances are observed when the predicted IR, 1H-NMR, 13C-NMR and UV-Vis spectra are compared with the corre-sponding experimental ones. Complete vibrational assignments together with the scaled force constants are reported. The new compound was evaluated in vitro for their antihyperglycemic activity against alpha- amylase and alpha-glucosidase enzymes. Compound 4 was found to be more potent with IC50 value of 30.63 mu M against alpha-glucosidase enzyme, compared to the reference drug "Acarbose" (IC50 = 113.60 mu M) and exhibited good inhibitory activity against alpha-amylase enzyme with IC50 value of 133.8 mu M as compared with the reference drug "Acarbose" (IC50 = 124.5 mu M). Additionally, in silico molecular docking studies were carried out to confirm the experimental observations and investigate the efficacy of the title com-pound. (c) 2023 Elsevier B.V. All rights reserved.