Sun Ning, Zheng Yuan-Yuan, Du Ruo-Lan, Cai Sen-Yuan, Zhang Kun, So Lok-Yan, Cheung Kwan-Choi, Zhuo Chao, Lu Yu-Jing, Wong Kwok-Yin
Department of Applied Biology and Chemical Technology and the State Key Laboratory of Chirosciences , The Hong Kong Polytechnic University , Kowloon , Hong Kong SAR , P.R. China . Email:
Institute of Natural Medicine and Green Chemistry , School of Chemical Engineering and Light Industry , Guangdong University of Technology , Guangzhou 510006 , P.R. China . Email:
Medchemcomm. 2017 Aug 22;8(10):1909-1913. doi: 10.1039/c7md00387k. eCollection 2017 Oct 1.
The filamenting temperature-sensitive mutant Z (FtsZ) protein is generally recognized as a promising antimicrobial drug target. In the present study, a small organic molecule (tiplaxtinin) was identified for the first time as an excellent cell division inhibitor by using a cell-based screening approach from a library with 250 compounds. Tiplaxtinin possesses potent antibacterial activity against Gram-positive pathogens. Both and results reveal that the compound is able to disrupt dynamic assembly of FtsZ and Z-ring formation effectively through the mechanism of stimulating FtsZ polymerization and impairing GTPase activity.
丝状温度敏感突变体Z(FtsZ)蛋白通常被认为是一个很有前景的抗菌药物靶点。在本研究中,通过基于细胞的筛选方法,从一个含有250种化合物的文库中首次鉴定出一种小分子有机化合物(替普拉西丁),它是一种出色的细胞分裂抑制剂。替普拉西丁对革兰氏阳性病原体具有强大的抗菌活性。体外和体内结果均表明,该化合物能够通过刺激FtsZ聚合和损害GTP酶活性的机制,有效破坏FtsZ的动态组装和Z环形成。