New aromatic hydrazones: Synthesis, structural analysis, DFT study, biological activity, ADME-T properties and in silico evaluation of their inhibition of SAS-CoV-2 main protease.

• Three aromatic hydrazones were prepared and characterized. • Spectral and structural properties of the prepared derivatives were studied. • Experimental results have been correlated by DFT method at B3LYP/6–311++ G (d,p). • The tested hydrazones are effective antioxidant and antibacterial agents. • The in silico study of the inhibition of SARS-CoV-2 main protease has been performed. Three new hydrazones namely: (2E)-1-(4-methylphenyl-2-[(thiophen -2- yl) methylidene ]hydrazine (HZ-1), (2E)-1-(4-methylphenyl)-2-[(thiophen -3 yl) methylidene ]hydrazine (HZ-2) and (1E)-1[(furan -2- yl) methylidene ]-2-(4methylphenyl)hydrazine (HZ-3) have been synthesized by reacting (4-methylphenyl)hydrazine with three heterocyclic aldehydes: 2-thiophenecarboxaldehyde, 3-thiophenecarboxaldehyde and 2-furaldehyde in ethanol at reflux 78 °C. The structures of these compounds were confirmed by spectroscopic and physicochemical methods such as UV–Vis, IR, melting point, 1H NMR and 13C NMR spectra. Their antioxidant activity was evaluated using DPPH, ABTS, FRAP, CUPRAC and phenanthroline assays. The obtained results indicate that the title molecules exhibit excellent activity better and comparable as standards BHT, BHA and ascorbic acid. Also, the synthesized compounds show a good antibacterial activity against two such: P. aeruginosa and B. subtilis. In addition, the density functional theory (DFT) is used to calculate the optimized molecular structures, electronic and vibrational spectra, reactivity, stability and some quantum chemical parameters of the synthesized molecules. The obtained theoretical results are in good agreement with the experimental results. Finally, in silico predictions of ADME-T and pharmacokinetic parameters indicated that these compounds should have good oral bioavailability. Also, the molecular docking has been used to predict the inhibitory activity of SARS-CoV-2 main protease (Mpro) of the studied hydrazones. [Display omitted] [ABSTRACT FROM AUTHOR]