Abstract
An efficient method using ZnO(NPs) was used to synthesize derivatives of s-substituted-1,2,4-triazoles with excellent yield. The structure of all newly formed triazoles was approved using the data extracted from their spectral and elemental analyses. Fifteen s-substituted-triazole derivatives were tested for their antimicrobial activity and the results indicated that triazole derivative 15 recorded the highest antimicrobial activity against Trichophyton mentagrophyte followed by Staphylococcus aureus and Bacillus cereus with clear zone diameters of 30, 28, and 15 mm when compared with the traditional antibiotics, with minimal lethal concentrations of 16, 32, and 64 mu g/ml, respectively. While compounds 13c, 13b, 13a and 8a exhibited considerable antimicrobial activity against Gram-positive pathogens including B. cereus, S. aureus. The docking study for the most potent derivatives 8a, 13a, 13b, 13c and 15 against methicillin acyl-Penicillin binding protein 2a from methicillin-resistant S. aureus strain 27r at 2.60 A resolution (PDB: 1MWU) showed strong fit in the active site the methicillin acyl-Penicillin binding protein, especially for derivative 15. Due to the horror caused by the Corona pandemic during the past two years, we docked the s-substituted-1,2,4-triazole derivatives into the active site of SARS-CoV-2 main protease (6LU7). The docking result showed well-fitting and proper orientation of all triazole derivatives except the starting derivative 5. The physicochemical properties, pharmacokinetics, and drug-likeness of the most active s-substituted-1,2,4-triazole derivatives were studied using SwissADME. The results of computational studies and in vitro antimicrobial activity showed great agreement, in addition to the docking study of COVID-19 revealed the ability of triazole derivatives to fit in the active site of the protein, which made us recommend laboratory tests for these triazole derivatives to prove their inhibition efficiency.