Synthesis, biological evaluation and induced fit docking simulation study of d-glucose-conjugated 1H-1,2,3-triazoles having 4H-pyrano[2,3-d]pyrimidine ring as potential agents against bacteria and fungi

Abstract

Some gluco-conjugated 1H-1,2,3-triazoles possessing 4H-pyrano[2,3-d]pyrimidines 8a–8s were synthesized via click chemistry between N-propargyl-4H-pyrano[2,3-d]pyrimidines 6a–6s and peracetylated glucopyranosyl azide 7, respectively. This process occurred under catalytic conditions using CuI@montmorillonite as the catalyst in absolute ethanol. The antibacterial, anti-MRSA and antifungal activities of these 1H-1,2,3-triazoles were probed using the minimum inhibitory concentration. Amongst the examined compounds, 1,2,3-triazoles 8g and 8s exhibited good inhibitory activity against the seven tested bacterial strains with MIC values in the range of 0.78–6.25 μg mL⁻¹. They also displayed excellent inhibitory activity against five clinically isolated MRSA strains with MIC values in the range of 0.78–3.125 μM, especially 8g, which exerted excellent activity against all tested MRSA strains and S. aureus with MIC values in the range of 0.78–1.56 μg mL⁻¹. An induced fit docking study was performed to observe the binding efficiency and steric interactions of the lead compound 8g. IFD results showed that compound 8g is compatible with the active site of S. aureus DNA gyrase 2XCS with six hydrogen bonding interactions and two π–π stacking interactions, which suggest that the tested compounds inhibit the synthesis of the S. aureus gyrase enzyme.