1,3,4-Oxadiazole derivatives as potential antifungal agents: Synthesis, characterization, Ct-DNA binding, molecular docking, and TD-DFT studies

Abstract 1,3,4-Oxadiazole-based heterocyclic analogs (3a–3m) were synthesized via cyclization of Schiff bases with substituted aldehydes in the presence of bromine and acetic acid. The structural clarification of synthesized molecules was carried out with various spectroscopic techniques such as FT-IR, 1H and 13C-NMR, UV–visible spectroscopy, mass spectrometry (LCMS). The TD-DFT studies were also confirmed the structure of drug molecules. In vitro antifungal activity was performed against C. Albicans, C. glabrata and C. tropicalis and analogs 3g, 3i, and 3m showed potent MIC at 200 µg/ml and excellent ZOI measurements of 17-21 nm. The cell viability on human hepatoma cells (Huh7) for lead molecules 3g, 3i, and 3m was found to be 99.5%, 92.3%, and 86.9% at 20 μM, 10 μM, and 20 μM respectively. The antioxidant activity of the lead molecules 3g, 3i, and 3m were estimated and exhibited great IC50 values of 0.104 ± 0.021, 0.145 ± 0.05, and 0.165 ± 0.018 μg/mL with DPPH and 0.107 ± 0.04, 0.191 ± 0.12, and 0.106 ± 0.08 with H2O2 respectively. The DNA binding interaction mode for the lead molecules was also carried out with Ct-DNA using the absorption, emission, CV, CD, and Time resolve fluorescence techniques. The results showed good binding constant (Kb) values 9.1×105, 9.94×105, and 9.32×105 M−1 for 3g, 3i, and 3m respectively. The results were further validated by In-silico molecular docking and pharmacokinetics properties of lead drug molecules were also studied with PDB ID: 1BNA and 5FSA to explore the best hits.