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, H-1 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 mu g/ml. The compounds 4b and 4c showed promising antioxidant activity at a concentration of 10 mu g/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.