Synthesis and inhibitory activity against MurA and MurZ enzymes of 4-pyrano[2,3-]pyrimidine-1-1,2,3-triazole hybrid compounds having piperidine and morpholine rings

A series of d -glucose-conjugated 4 H -pyrano[2,3- d ]pyrimidine-1 H -1,2,3-triazole hybrid compounds 12a-g and 13a-g having piperidine and morpholine rings were synthesized by click chemistry between corresponding propargyl derivatives and azide of d -glucose using CuI@montmorillonite as a catalyst. Their inhibitory activities against E. coli MurA and S. aureus MurA and MurZ enzymes were examined. The morpholine ring at position 3 along with the ethoxy group at position 4 on the benzene nucleus made 1,2,3-triazole 13b become the most potent inhibitor in this series against all three enzymes, E. coli MurA as well as S. aureus MurA and MurZ with IC 50 values of 0.15 0.05, 1.02 ± 0.05, and 1.21 ± 0.05 μM, respectively. This compound also exhibited a strong bacterial growth inhibitory activity against E. coli and S. aureus with MIC values of 0.78 and 1.56 μg mL −1 , respectively. Induced fit docking and molecular dynamics simulations were carried out on enzyme 1UAE in order to elucidate the inhibition potential of 13b against corresponding tested enzyme UDP- N -acetylglucosamine enolpyruvyl transferase MurA. A series of 1 H -1,2,3-triazoles 12a-g and 13a-g having 4 H -pyrano[2,3- d ]pyrimidine and d -glucose rings was synthesized by click chemistry and their inhibitory activity against UDP- N -acetylglucosamine enolpyruvyl transferases (MurA & MurZ) was examined.