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

Autor: Ning Sun, Yu-Jing Lu, Fung-Yi Chan, Ruo-Lan Du, Yuan-yuan Zheng, Kun Zhang, Lok-Yan So, Ruben Abagyan, Chao Zhuo, Yun-Chung Leung, Kwok-Yin Wong
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Frontiers in Microbiology, Vol 8 (2017)
Druh dokumentu: article
ISSN: 1664-302X
DOI: 10.3389/fmicb.2017.00855
Popis: 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.
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