Investigation of new 1,2,3-triazolyl-quinolinyl-propan-2-ol derivatives as potential antimicrobial agents: and approach.

A new series of 1-((1-(4-substituted benzyl)-1-1,2,3-triazol-4-yl)methoxy)-2-(2-substituted quinolin-4-yl)propan-2-ol () have been synthesized. The newly synthesized 1,2,3-triazolyl-quinolinyl-propan-2-ol () derivatives were screened for antimicrobial activity against H37Rv, , , , and . Most of the compounds showed good to moderate antibacterial activity and all derivatives have shown excellent to good antitubercular activity with MIC 0.8-12.5 μg/mL. To know the plausible mode of action for antibacterial activity the docking study against DNA gyrase from and was investigated. The compounds have shown significant docking scores in the range of -9.532 to -7.087 and -9.543 to -6.621 Kcal/mol with the DNA gyrase enzyme of (PDB ID: 2XCT) and (PDB ID: 5BS8), respectively. Against the and H37Rv strains, the compound showed good activity with MIC values of 62.5 and 3.33 μM. It also showed significant docking scores in both targets with -8.291 and -8.885 Kcal/mol, respectively. Molecular dynamics was studied to investigate the structural and dynamics transitions at the atomistic level in DNA gyrase (2XCT) and DNA gyrase (5BS8). The results revealed that the residues in the active binding pockets of the and DNA gyrase proteins that interacted with compound remained relatively consistent throughout the MD simulations and thus, reflected the conformation stability of the respective complexes. Thus, the significant antimicrobial activity of derivatives recommended that these compounds could assist in the development of lead compounds to treat for bacterial infections.Communicated by Ramaswamy H. Sarma.