1. A Thiazole Orange Derivative Targeting the Bacterial Protein FtsZ Shows Potent Antibacterial Activity
- Author
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Sun, Ning, Lu, Yu-Jing, Chan, Fung-Yi, Du, Ruo-Lan, Zheng, Yuan-yuan, Zhang, Kun, So, Lok-Yan, Abagyan, Ruben, Zhuo, Chao, Leung, Yun-Chung, and Wong, Kwok-Yin
- Subjects
Microbiology ,Biological Sciences ,Biomedical and Clinical Sciences ,Clinical Sciences ,Prevention ,Biodefense ,Infectious Diseases ,Vaccine Related ,Emerging Infectious Diseases ,Antimicrobial Resistance ,5.1 Pharmaceuticals ,Development of treatments and therapeutic interventions ,Infection ,bacterial resistance ,antibacterial activity ,cell division ,FtsZ inhibitor ,FtsZ polymerization ,Environmental Science and Management ,Soil Sciences ,Medical microbiology - Abstract
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.
- Published
- 2017