Synthesis, characterization, DFT calculation, antifungal, antioxidant, CT-DNA/pBR322 DNA interaction and molecular docking studies of heterocyclic analogs

Abstract

A series of heterocyclic analogs (2a-2l) was synthesized through condensation of 5-(4-aminophenyl)-1,3,4-oxadiazole-2-thiol and substituted aldehydes in ethanol and characterized by 1H, 13C NMR, IR, UV–visible spectroscopy and mass spectrometry. Optimization of the structure of heterocyclic analogs 2c, 2h and 2j was done by density functional theory (DFT) calculations. In vitro antifungal activity and growth pattern analyses of heterocyclic analogs (2a-2l) were evaluated against the Candida albicans. Results exhibited that analog 2c has significant antifungal potential with MIC value of 200 µg/ml comparable with standard drug fluconazole. In vitro hemolysis assay of the analog 2c showed 7.27% hemolysis at 200 µg/ml concentration indicating its nontoxic nature. The interaction of promising compound 2c with CT-DNA was carried out by UV-visible, fluorescence, Time-Resolved fluorescence spectrophotometry, cyclic voltammetry, circular dichroism and viscosity measurements. The UV-visible spectral analysis signifies the formation of complex between heterocyclic analog 2c and CT-DNA. The binding constant (Kb) and Gibb's free energy (ΔG) for 2c were found to be 6.34 × 105 and -33.1 KJmol−1, respectively. Further from fluorescence spectra, linear Stern–Volmer constant (KSV) for 2c was found to be 1.29 × 105. In silico molecular docking study of analog 2c with PDB: 1BNA confirmed the intercalation mode of binding which were corroborated with in vitro DNA binding results. The interaction study of analog 2c with supercoiled pBR322 plasmid DNA with varying concentration (3–20 mM) was carried out by Agarose gel electrophoresis. Antioxidant activity was also carried out for compounds 2a-2l using DPPH and H2O2 assay.