A Thiazole Orange Derivative Targeting the Bacterial Protein FtsZ Shows Potent Antibacterial Activity.

The prevalence of multidrug resistance among clinically significant bacteria calls for the urgent development of new antibiotics with novel mechanisms of action. In this study, a new small molecule exhibiting excellent inhibition of bacterial cell division with potent antibacterial activity was discovered through cell-based screening. The compound exhibits a broad spectrum of bactericidal activity, including the methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and NDM-1 Escherichia coli. The in vitro and in vivo results suggested that this compound disrupts the dynamic assembly of FtsZ protein and Z-ring formation through stimulating FtsZ polymerization. Moreover, this compound exhibits no activity on mammalian tubulin polymerization and shows low cytotoxicity on mammalian cells. Taken together, these findings could provide a new chemotype for development of antibacterials with FtsZ as the target

Study of Benzofuroquinolinium Derivatives as a New Class of Potent Antibacterial Agent and the Mode of Inhibition Targeting FtsZ

New generation of antibacterial agents are urgently needed in order to fight the emergence of multidrug-resistant bacteria. FtsZ is currently identified as a promising target for new types of antimicrobial compounds development because of its conservative characteristics and its essential role played in bacterial cell division. In the present study, the antibacterial activity of a series of benzofuroquinolinium derivatives was investigated. The results show that the compounds possess potent antibacterial activity against drug resistant pathogens including MRSA, VREF and NDM-1 Escherichia coli. Biological studies reveal that the compound is an effective inhibitor that is able to suppress FtsZ polymerization and GTPase activity and thus stopping the cell division and causing cell death. More importantly, this series of compounds shows low cytotoxicity on mammalian cells and therefore they could be new chemotypes for the development of new antibacterial agents targeting the cell-division protein FtsZ