Synthesis and characterization of novel xanthones appended with 1,2,3–triazoles: antimicrobial screening, in silico docking and ADMET predictions

In this paper, we report the design, synthesis, and characterization of novel 1,2,3–triazole hybrid conjugates, which were studied for their antimicrobial properties and in silico behaviour. The synthesized compounds consist of xanthone and 1,2,3–triazole structures with diverse substituents. In this study, a library of 1,2,3–triazoles was characterized using 1 H NMR, 13 C NMR, and HRMS. All derivatives were screened for their antibacterial and antifungal activity; out of all the synthesized compounds, derivative 5i exhibited the highest potency as an S. aureus inhibitor with an MIC value of 4.0 ± 0.17 μg/mL. Also, 5h exhibited promising antifungal inhibitory potential with an MIC value of 5.9 ± 0.42 μg/mL compared to Clotrimazole (MIC = 6.9 ± 0.23 μg/mL). In addition, the antimicrobial results showed that the most potent molecules ( 5a, 5d, 5h, and 5i ) showed inhibition effects against most of the tested microbes at low concentrations. Molecular docking studies indicated binding affinities of selected compounds to DNA gyrase B from E. coli (PDB code: 6KZV ) and penicillin binding protein 4 (PBP4) from S. aureus (5TW8) enzymes with residues HIS55, LYS57, ASP74, GLN72, THR163, ARG206, GLY75, CYS56, and SER92, respectively. In silico analyses of pharmacokinetic and physicochemical properties demonstrated that the majority of the compounds adhered to Lipinski's rule of five. To support the experimental data, molecular docking and ADME-T studies help in understanding the interactions better.