AUTHOR=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 , Wong Kwok-Yin 

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

JOURNAL=Frontiers in Microbiology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2017.00855

DOI=10.3389/fmicb.2017.00855

ISSN=1664-302X

ABSTRACT=<p>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 <italic>Staphylococcus aureus</italic>, vancomycin-resistant <italic>Enterococcus</italic> and NDM-1 <italic>Escherichia coli</italic>. The <italic>in vitro</italic> and <italic>in vivo</italic> 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.</p>