Document Detail


Synergistic fungicidal activities of amphotericin B and N-methyl-N"-dodecylguanidine: a constituent of polyol macrolide antibiotic niphimycin.
MedLine Citation:
PMID:  17390586     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The synergy between the alkylguanidinium chain of niphimycin (NM), a polyol macrolide antibiotic, and polyene macrolide amphotericin B (AmB) without such an alkyl side chain was examined using N-methyl-N"-alkylguanidines as its synthetic analogs. Among the analogs, N-methyl-N"-dodecylguanidine (MC12) most strongly inhibited the growth of Saccharomyces cerevisiae cells and those of other fungal strains in synergy with AmB. MC12 itself was not lethal but the analog could be a cause of a rapid cell death progression of yeast cells in the presence of AmB at a nonlethal concentration. Their combined actions resulted in the generation of NM-like fungicidal activity that depended on plasma membrane disability and cellular reactive oxygen species production. We also found an aberrant vacuolar morphogenesis and an associated vacuolar membrane disability in cells treated simultaneously with MC12 and AmB, as in the case of NM-treated cells. These findings support the idea that the alkylguanidinium chain plays a major role in the fungicidal activity of NM in cooperation with the polyol lactone ring as its enhancer.
Authors:
Akira Ogita; Keiji Matsumoto; Ken-ichi Fujita; Yoshinosuke Usuki; Yoshiro Hatanaka; Toshio Tanaka
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of antibiotics     Volume:  60     ISSN:  0021-8820     ISO Abbreviation:  J. Antibiot.     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2007-03-29     Completed Date:  2007-04-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0151115     Medline TA:  J Antibiot (Tokyo)     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  27-35     Citation Subset:  IM    
Affiliation:
Research Center for Urban Health and Sports, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan.
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MeSH Terms
Descriptor/Qualifier:
Amphotericin B / pharmacology*
Antifungal Agents / pharmacology*
Cell Membrane / drug effects
Cell Membrane Permeability / drug effects
Drug Synergism
Guanidines / pharmacology*
Microbial Sensitivity Tests
Microbial Viability
Microscopy, Electron, Transmission
Microscopy, Fluorescence
Molecular Structure
Reactive Oxygen Species / metabolism
Saccharomyces cerevisiae / drug effects*,  growth & development,  ultrastructure
Vacuoles / drug effects,  ultrastructure
Chemical
Reg. No./Substance:
0/Antifungal Agents; 0/Guanidines; 0/N-methyl-N''-dodecylguanidine; 0/Reactive Oxygen Species; 1397-89-3/Amphotericin B

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