Synthesis, Structural Investigations, DFT Calculations, and Molecular Docking Studies of Novel 2-(Substituted-Aryloxymethyl)-5-(Pyridin-4-yl)-1, 3, 4-Oxadiazoles: Highly Potential InhA and Cytochrome c Peroxidase Inhibitors

We report derivatives of 2,5-disubstituted-1,3,4-oxadiazole as powerful anti-TB and antioxidant compounds. Using substituted aryloxy acetic acids (2a–f) and isoniazid (3) in the presence of phosphorus oxychloride, a series of new 2-(substituted-aryloxymethyl)-5-(pyridin-4-yl)-1,3,4-oxadiazoles (4a–f) are synthesized. IR, 1H NMR, and mass spectral data were used to physically and spectroscopically describe the synthesized molecules. Density Functional Theory (DFT) calculations were performed at the DFT/B3LYP level using 6-31 G++ (d, p) to reproduce the structure and geometry. The non-linear visual characteristic of compounds is determined by the first-order hyperpolarizability calculation. To analyze the charge transfer interface between the structures, HOMO and LUMO investigations were used. The in vitro anti-TB and antioxidant activity was carried out. The compound 4d exhibited excellent anti-TB activity with a MIC value of 3.12 µg/ml. The compounds 4b and 4c showed promising antioxidant activity at a concentration of 10 µg/ml with inhibition rates of 68.36% and 69.26% respectively. Furthermore, the docking studies for the newly synthesized molecules were carried out by Auto dock software with proteins InhA (4TZK) and Cytochrome c peroxidase (2X08). All the compounds showed a strong binding affinity for the docked proteins.