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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    
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.
Parminder Singh; Bhavya Jindal; Avadhesha Surolia; Dulal Panda
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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:  -    
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