| A rhodanine derivative CCR-11 inhibits bacterial proliferation by inhibiting the assembly and GTPase activity of FtsZ. | |
| | |
MedLine Citation:
|
PMID: 22703373 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
A perturbation of FtsZ assembly dynamics has been shown to inhibit bacterial cytokinesis. In this study, the antibacterial activity of 151 rhodanine compounds was assayed using Bacillus subtilis cells. Out of 151 compounds,8 compounds strongly inhibited bacterial proliferation at 2 µM. Subsequently, we used the elongation of B.subtilis cells as a secondary screen to identify potential FtsZ-targeted antibacterial agents. We found that 3 compounds significantly increased the bacterial cell length. One of the three compounds namely, CCR-11 ((E)-2-thioxo-5-((-(3-(trifluoromethyl)phenyl)furan-2-yl)methylene)thiazolidin-4-one) inhibited the assembly and GTPase activity of FtsZ in vitro. CCR-11 bound to FtsZ with a dissociation constant of 1.5 ± 0.3 µM. A docking analysis indicated that CCR-11 may bind to FtsZ in a cavity adjacent to the T7 loop and that short halogen-oxygen, H-bonding and hydrophobic interactions might be important for the binding of CCR-11 with FtsZ. CCR-11 inhibited the proliferation of B. subtilis cells with a half-maximal inhibitory concentration (IC(50)) of 1.2 ± 0.2 µM and a minimum inhibitory concentrationof 3 µM. It also potently inhibited proliferation of Mycobacterium smegmatis cells. Further, CCR-11 perturbed the Z-ring formation in B. subtilis cells; however, it neither visibly affected the nucleoid segregation nor altered the membrane integrity of the cells. CCR-11 inhibited HeLa cell proliferation with an IC(50) value of 18.1 ± 0.2 µM (~15 × IC(50) of B. subtilis cell proliferation). The results suggested that CCR-11 inhibits bacterial cytokinesis by inhibiting FtsZ assembly and it can be used as a lead molecule to develop FtsZ-targeted antibacterial agents. |
| | |
Authors:
|
Parminder Singh; Bhavya Jindal; Avadhesha Surolia; Dulal Panda |
Related Documents
:
|
22826803 - Global dispersion of bacterial cells on asian dust. 22622133 - In vitro differentiation of mouse embryonic stem cells into inner ear hair cell-like ce... 14255713 - Comparison of the cell-wall composition of morphologically distinct actinomycetes. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-6-18 |
Journal Detail:
|
Title: Biochemistry Volume: - ISSN: 1520-4995 ISO Abbreviation: - Publication Date: 2012 Jun |
Date Detail:
|
Created Date: 2012-6-18 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0370623 Medline TA: Biochemistry Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Asystole to cross-clamp period predicts development of biliary complications in liver transplantatio...
Next Document: Outcomes of a Headache-Specific Cross-Sectional Multidisciplinary Treatment Program.