Chemical Physics Impact (Dec 2024)
Effect of intermolecular interactions and pharmacokinetic profile of antidiabetic agent (E)-N,N‑diethyl-2-(5(3‑hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl) acetamide
Abstract
Diabetes is a prevalent disease in South India, posing a severe threat to public health. To tackle this issue, researchers are focusing on developing multi-targeted ligands, and one promising candidate is (E)-N,N‑diethyl-2-(5(3‑hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetamide (DMDA). Geometry optimization of DMDA was carried out using density functional theory with 6–311+G(d, p) basis set to develop a theoretical model close to the previously synthesized and reported DMDA. Natural Bond Orbital analysis was conducted to scrutinize the phenomena of charge delocalization and electronic exchange interactions governing both intermolecular and intramolecular associations. Moreover, the vibrational characteristics of the molecule were elucidated through FT-IR and FT-Raman spectra. Lowest Unoccupied Molecular Orbital and Highest Occupied Molecular Orbital have also been explored to enhance understanding of the molecule's electronic structure and reactivity. Hirshfeld surface analysis was utilized to investigate the interactions between molecules within the crystalline lattice. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis elucidates the potential pharmacokinetic profile of DMDA. Molecular docking was performed to predict the binding site responsible for various interactions with the targeted protein. By combining these techniques, a comprehensive molecular description of DMDA has been generated.There are three prominent intramolecular interactions within the ambit of van der Waals radii, leading to stability of the molecule. The presence of a broad and shallow band with a significant red shift provides evidence for the strong intermolecular OH hydrogen bonding. DMDA complies with Lipinski's Rule of Five, highlighting its favorable characteristics for pharmaceutical efficacy. The negative binding energies determined by docking studies ascertain the potential sites of ligand-protein interaction leading to inhibition of α-amylase and α-glucosidase enzyme.
