Synthesis, antimicrobial activity and in-silico studies of (1-(1-arylethyl)-1H-1,2,3-triazolyl-2-phenylquinoline-4-carboxylate derivatives with click chemistry.

A new series of (1-(1-arylethyl)-1H-1,2,3-triazol-4-yl)methyl-2-phenylquinoline-4-carboxylate derivatives 6a-s has been synthesized. The synthesized compounds were characterized by IR and NMR spectroscopy and mass spectrometry. The in vitro antimicrobial activity of the prepared compounds against E. coli, P. mirabilis, B. subtilis, S. aureus, C. albicans and A. niger strains were investigated. Most of the (1-(1-arylethyl)-1H-1,2,3-triazolyl-2-phenylquinoline-4-carboxylate derivatives showed good antifungal activity. Against A. niger, nine compounds 6h, 6l, 6m, 6n, 6o, 6p, 6q, 6r, and 6 s showed good activity and against C. albicans, six compounds 6c, 6d, 6h, 6k, 6p and 6q showed good activity with MIC 31.25-62.50 μg/mL. The compounds 6l and 6q showed good activity against E. coli, compound 6p found potent against E. coli and S. aureus. The compounds 6h and 6r showed good activity against B. subtilis. The compound (1-(1-(4-chlorophenyl)ethyl)-1H-1,2,3-triazol-4-yl)methyl-6-fluoro-2-phenylquinoline-4-carboxylate 6p showed broad spectrum of antimicrobial activity. The in-silico studies of the synthesized compounds demonstrated strong binding affinity values (≤ -12.0 kcal/mol). Molecular docking analysis of compounds 6a-s showed robust interactions with the target protein 5FRB, suggesting their potential to inhibit sterol 14-α-demethylase (CYP51B). Furthermore, molecular dynamics simulations confirmed that the ligand-protein complexes 5FRB_6 h and 5FRB_6q maintained structural stability throughout the 100 ns trajectory.