1,3,4-oxadiazole derivatives: synthesis, characterization, antifungal activity, DNA binding investigations, TD-DFT calculations, and molecular modelling.
Journal:
Journal of biomolecular structure & dynamics
PMID:
39886763
Abstract
1,3,4-Oxadiazole-based heterocyclic analogs (3a-3m) were synthesized 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,H and C-NMR, UV-visible spectroscopy, and mass spectrometry. antifungal activity was performed against , and 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 Huh7 for lead molecules 3g, 3i, and 3m was found to be 99.5%, 92.3%, and 86.9% at 20, 10, and 20 μM, respectively. The antioxidant activity of molecules 3 g, 3i, and 3 m was estimated and exhibited great IC 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 HO, respectively. The 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 (K) values of 9.1 × 10, 9.94 × 10, and 9.32 × 10 M for 3g, 3i, and 3m, respectively. TD-DFT study of compounds 3g, 3i, and 3m was done to find out HOMO/LUMO energy levels, surface study of the molecular electrostatic potential, Mulliken population analysis, and natural bond orbitals showing the linkages between the donors and acceptors.Molecular docking of three lead analogs with PDB ID: 1BNA and molecular modelling of compounds 3g, 3i, and 3m with CYP51 protein (PDB ID: 5FSA) were carried out.Communicated by Ramaswamy H. Sarma.