Synthesis and In silico Molecular Docking Studies of Tetrazole and Thiazole - Based Schiff Base Derivatives as Antibacterial and Antioxidant Agents

Abstract

Nowadays, alarming and reemerging multidrug resistance bacteria are becoming a major public health concerns. Antibacterial activities of the synthesized compounds were examined using agar disk diffusion method against S. aureus, E. coli, S. pyogenes and P. aeruginosa strains. Compounds 106, 101, and 105 showed good activities against E. coli with mean inhibition zone of 14.4  0.04, 12.5  .04 and 10.5  0.02mm diameter at 200 μg/mL compared to Amoxicillin (18  0.01, respectively. Of the synthesized compounds, compound 106 displayed the highest activity with zone of inhibition of 14.4  0.04, 15  0.01, 13  0.02, and 14.45  0.25 at 200 μg/mL against E. coli, S. aureus, P. aeruginosa, and S. pyogenes, respectively. Compound 102, 105 and 101 exhibited highest percent inhibition of the DPPH with IC50 value of 3.6, 3.65 and 4.91 in μg/mL, respectively. Molecular docking analysis of synthesized compounds against DNA gyrase B showed minimum binding energy ranging from -7.5 to -6 kcal/mol of which best binding affinity was achieved for compounds 106, 101 and 105 (-7.5, -7.2 and -6.9 kcal/mol, respectively. Compounds 101 and 106 showed better binding affinity compared to standard drug, Amoxicillin. The docking analysis against human peroxiredoxin 5 revealed minimum binding energy ranging from - 5.3 to - 5.0 kcal/mol of which compounds 101, 102, 105 and 104 showed better binding affinity (-5.3, -5.3, -5.2 and -5.1 kcal/mol, respectively) compared to standard drug, Ascorbic acid. In vitro antibacterial activity of compounds 106, 101, 105 and antioxidant activity of compounds 102, 105 and101 suggest the potential use of these compounds as potential drug lead candidates, supported by both experimental and computational analysis. Compounds 105 and 106 showed significant molecular interactions with topoisomerase II at active sites (- 5.8, - 5.9, kcal/mol, respectively) compared to Vosaroxin (- 6.2, kcal/mol). In silico cytoxicity predictions revealed LD50 value of class three (50 ≤ LD50 ≤ 300) inferring they are toxic if swallowed except compound 101 (class 4, 300 ≤ LD50 ≤ 2000). The DFT and wave function analysis revealed that compound 102 showed the least HOMO-LUMO energy gap suggesting high chemical reactivity and considerable intramolecular charge transfer from electron donor (HOMO) to electron acceptor (LUMO) groups. However, except compound 101 all compounds showed small band gap energy ranging from 0.134-0.692 eV inferring good reactivity of molecules.