Synthesis, characterization and biological investigations of some new Oxadiazoles: In-vitro and In-Silico approach

Abstract

A series of new oxadiazole derivatives, namely 1-{2-substituted phenyl −5-[2-tifluoromethyl)-1H-indol-3-yl]-3-(2H)-ylethanone 1,3,4-oxadiazoles were synthesized and investigated in this research. Using AutoDockVina 4.2, the new compounds VIb and VIc were extensively investigated for their ADMET characteristics and in-silico drug receptor interactions with the target enzyme, GlcN-6-P synthase (PDB ID: 2FV5). The existence of an electron-withdrawing group and a lipophilic functional group substituted at the phenyl ring was observed to be more active than in other molecules. The new molecules drug ability was investigated using ADMET experiments performed by Swiss ADME software, and the newly synthesized compounds qualified for ADME characteristics and followed Lipinski’s rule of five. FTIR, 1H NMR, 13CNMR, and mass spectrometry tools were used to characterize the prepared substances. The prepared substances were screened for antibacterial activity against gram-positive (Bacillus subtilis, Staphylococcus aureus) and gram-negative microbes (Pseudomonas aeruginosa and Escherichia coli) using cup plate and MIC techniques. These substances were also screened for antifungal activity against Aspergillus niger and Candida albicans, with Ampicillin and Amphotericin B serving as standard references. The compounds VIb and VIc have more antibacterial action than antifungal activity among the synthesized substances. Compounds VIa to VIf were examined for in vitro antioxidant activity and compounds VIb and VIc has displayed significant antioxidant potentials with IC50 values 45.16 and 38.14 in DPPH assay. The compounds VIa–f were tested for anticancer activity using MDA-MB 361 cell lines using MTT assays, and the IC50 values were recorded, out of which VIb and VIc displayed the lowest IC50 values. In-silico drug receptor interactions with the target enzyme, phosphoinositide-3-kinase (PI3K), with PDB ID: 3MJW were predicted as supportive evidence for the anticancer properties of the synthesized scaffolds.