New Triazole-Isoxazole Hybrids as Antibacterial Agents: Design, Synthesis, Characterization, In Vitro, and In Silico Studies.

Novel isoxazole-triazole conjugates have been efficiently synthesized using 3-formylchromone as starting material according to a multi-step synthetic approach. The structures of the target conjugates and intermediate products were characterized by standard spectroscopic techniques (H NMR and C NMR) and confirmed by mass spectrometry (MS). The all-synthesized compounds were screened for their antibacterial activity against three ATCC reference strains, namely ATCC 25923, ATCC BAA-44, and ATCC 25922 as well as one strain isolated from the hospital environment . The findings indicate that conjugate 7b exhibits a stronger antibacterial response against the tested ATCC 25922 and pathogenic strains compared to the standard antibiotics. Furthermore, hybrid compound proved to have a bactericidal action on the ATCC 25922 strain, as evidenced by the results of the MBC determination. Moreover, the ADMET pharmacokinetic characteristics revealed a favorable profile for the examined compound, as well as a good level of oral bioavailability. Molecular docking and molecular dynamics simulations were performed to explore the inhibition mechanism and binding energies of conjugate with the proteins of and bacterial strains. The in silico results corroborated the data observed in the in vitro evaluation for compound .