Discovery of novel FtsZ inhibitors with antimicrobial activity by virtual screening and in vitro biological evaluation

Filamentous temperature-sensitive protein Z (FtsZ) plays an important role in bacterial division, and the inhibition of normal physiological function of FtsZ can make a devastating effect on bacterial growth and proliferation, which making it an important antibacterial target. The inhibitor activity targeting the cleft between the H7 helix and the C-terminal substructural domain exhibited superior binding compared to the GTP binding site. Therefore, the discovery of inhibitors targeting the cleft as a binding site holds promise for further research. By performing virtual screening with the workflow mainly composed of pharmacophore modeling and molecular docking as well as the following FtsZ inhibition assay, we identified four compounds B6 , B21 , B26 and B31 . Futher experiment showed that compound B6 and B26 possessed antimicrobial activity with MIC values of 8 µg-mL-1 and 32 µg-mL-1. In conclusion, our study successfully identified novel FtsZ inhibitors with antimicrobial activity through virtual screening and in vitro biological evaluation, demonstrating their potential for further investigation.