Investigation of Novel 2‐(Chloromethyl)‐5‐(3, 5‐Disubstituted‐1H‐Indol‐2‐yl)‐1,3,4‐Oxadiazole Derivatives as In Vitro, and In Silico Bioactivity Potential: Anti‐inflammatory, Anti‐TB and Antioxidant Activities Study

Abstract

AbstractA series of novel 2‐(chloromethyl)‐5‐(3, 5‐disubstituted‐1H‐indol‐2‐yl)‐1,3,4‐oxadiazole (3 a–h) derivatives have been synthesized as potential COX inhibitors, anti‐TB, and anti‐oxidant activities. The structures were confirmed by IR, NMR (1H and 13C) mass spectral techniques. The physicochemical properties, ADME, and drug‐likeness profile for the synthesized compounds were evaluated by SwissADME. Based on our interest in indole chemistry and SAR study, foresaid indole compounds were examined for in vitro COX inhibitory activity, anti‐TB, and antioxidant activities. The physicochemical and ADME studies were disclosed for newly synthesized compounds. The compounds 3 a,3 b and 3 c recognized outstanding COX‐II inhibitions with IC50 values of 0.28, 0.24, and 0.45 μM compared to standard drugs. The compounds 3 a,and3 b showed outstanding anti‐TB activity with MIC value 0.78 μg/mL. The compounds 3 a,3 b, and 3 c attested outstanding antioxidant activity at 10 μg/ml with a rate of inhibition of 66.52 %, 68.25 %, and 65.95 % respectively. Finally, the molecular docking studies carried out with cyclooxygenase‐2 (PDB ID: 6COX), M. tuberculosis enoyl reductase (INHA) complexed with 1‐cyclohexyl‐N‐(3,5‐dichlorophenyl)‐5‐oxopyrrolidine‐3‐carboxamide (PDB ID: 4TZK), and cytochrome c peroxidase (PDB ID: 2X08), for all the newly synthesized derivatives. Finally, selected compounds were taken for their molecular dynamic studies.