Microwave-Assisted Rapid and Efficient Synthesis of Novel Indazole-Based 1,3,4-Oxadiazole Derivatives with Molecular Docking, ADME, and DFT Studies

Abstract

A novel and efficient synthetic protocol has been developed for the preparation of indazole-1,3,4-oxadiazoles through microwave-assisted reactions, using both aromatic and aliphatic carboxylic acids as starting materials. The structural identification and purity of the synthesized compounds were confirmed using IR, ¹H NMR, ¹³C NMR, and HRMS spectral data. Additionally, their photophysical properties were characterized using ultraviolet–visible (UV–vis) and fluorescence spectroscopy to determine the absorption maxima and emission wavelengths. Among the synthesized derivatives, four compounds 8h, 8l, 13c, and 13d that exhibited the least energy band gaps were selected for detailed computational analysis using DFT. TD-DFT calculations were conducted to predict the theoretical UV–vis absorption spectra, which were then compared with experimental data, including molar extinction coefficients, Stokes shifts, and fluorescence quantum yields. Molecular docking studies were performed using AutoDock Version 1.5.6, along with structural data from the protein data bank (PDB ID: 4EJN), to evaluate the binding affinities of all derivatives. Compounds 8h, 8j, 13h, and 13j showed the most favorable binding energies. Finally, the pharmacokinetic and drug-likeness profiles of the compounds were evaluated using the SWISS ADME platform, which provided insights into their physicochemical properties and visualized gastrointestinal absorption and blood–brain barrier permeability through the BOILED-Egg predictive model.