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Title: Indole-core-based novel antibacterial agent targeting FtsZ
Authors: Yuan, WC
Yu, ZW
Song, WQ
Li, YN
Fang, ZY
Zhu, BZ
Li, XM
Wang, H
Hong, W
Sun, N 
Issue Date: 2019
Source: Infection and drug resistance, 2019, v. 12, p. 2283-2296
Abstract: Background: The prevalence of drug-resistant bacterial infections urges the development of new antibacterial agents that possess a mechanism of action different from traditional antibiotics. FtsZ has been recognized as a key functional protein in bacterial cell division and it is currently believed to be a potential target for the development of novel antibacterial agents.
Purpose: The primary aim of the study is to screen out an inhibitor targeting at FtsZ and followed to investigate its antibacterial activity and mode of action.
Methods: Cell-based cell division inhibitory screening assay, antimicrobial susceptibility test, minimum bactericidal concentration assay, time-killing curve determination, FtsZ polymerization assay, GTPase activity assay, and molecular modeling were performed in the present study.
Results: The screening study from a small library consisting of benzimidazole and indole derivatives discovered a compound (CZ74) with an indole-core structure. The compound exhibited strong cell division inhibitory effect. In addition, CZ74 shows high antibacterial potency against a number of tested Gram-positive bacteria, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. The minimum inhibitory concentration values obtained were within the range of 2-4 mu g/mL. The results of biological study revealed that CZ74 at 2 mu g/mL is able to disrupt FtsZ polymerization and inhibit GTPase activity and cell division. From molecular modeling study, CZ74 is found possibly binding into the interdomain cleft of FtsZ protein and then leads to inhibitory effects.
Conclusion: This indole-cored molecule CZ74 could be a potential lead compound and could be further developed as a new generation of antibacterial agents targeting FtsZ to combat against multidrug-resistant bacteria.
Keywords: Indole-core-based derivative
Cell division
Antibiotic resistant
Publisher: Dove Medical Press
Journal: Infection and drug resistance 
EISSN: 1178-6973
DOI: 10.2147/IDR.S208757
Rights: © 2019 Yuan et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (
The following publication Yuan, W. C., Yu, Z. W., Song, W. Q., Li, Y. N., Fang, Z. Y., Zhu, B. Z., . . . Sun, N. (2019). Indole-core-based novel antibacterial agent targeting FtsZ. Infection and Drug Resistance, 12, 2283-2296 is available at
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