Quinolone Tethered 1,2,3-Triazole Conjugates: Design, Synthesis, and Molecular Docking Studies of New Heterocycles as Potent Antimicrobial Agents

Our current work is aimed to synthesizing novel derivatives of 1,2,3-triazolyl-2-quinolone and applying docking studies and biological activity evaluation in order to find active promising molecules. We succeeded in the development of a synthetic method towards 1,2,3-triazole substituted quinolone derivatives. The structures of the newly synthesized derivatives are characterized by IR, proton, carbon nuclear magnetic resonance spectroscopy, mass and elemental analysis. The antibacterial activity against both Gram-positive and Gram-negative bacteria is shown to be demonstrated by many of the produced compounds. On the other hand, the following compounds tert -butylphenyl-1,2,3-triazole, trifluoromethylphenyl-1,2,3-triazole, 3-nitrophenyl-1,2,3-triazole, 4-hydroxy-3-nitrophenyl-1,2,3-triazole, 4-hydroxy-4-trifluoromethylbenzyl-1,2,3-triazole, and 4-hydroxy-2,4-difluorobenzyl-1,2,3-triazole showed promising antibacterial, and antifungal activity with MIC values range 1.07–4.33 µg/mL. The prepared ligand 4-hydroxy-4-trifluoromethylbenzyl-1,2,3-triazole exhibited good docking score (–5.48 kcal/mol) and interacting amino acid residues ArgA:363, ProA:359, MetA:362, AlaA:361, AlaA:360, SerA:325, TyrA:364, ProA:358, TyrA:328, AspA:329, AspA:324 within the active site S. pneumoniae (4Z3O). These compounds were further evaluated for their ADMET and physicochemical properties by using SwissADME.