Document Detail


Beta-cyclodextrin derivatives that inhibit anthrax lethal toxin.
MedLine Citation:
PMID:  16169738     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recently, we demonstrated that simultaneous blocking of bacterial growth by antibiotics and inhibition of anthrax toxin action with antibodies against protective antigen were beneficial for the treatment of anthrax. The present study examined the hypothesis that blocking the pore formed by protective antigen can inhibit the action of anthrax toxin. The potential inhibitors were chosen by a structure-based design using beta-cyclodextrin as the starting molecule. Several beta-cyclodextrin derivatives were evaluated for their ability to protect RAW 264.7 cells from the action of anthrax lethal toxin. Per-substituted aminoalkyl derivatives displayed inhibitory activity and were protective against anthrax lethal toxin action at low micromolar concentrations. These results provide the basis for a structure-based drug discovery program, with the goal of identifying new drug candidates for anthrax treatment.
Authors:
Vladimir A Karginov; Adiamseged Yohannes; Tanisha M Robinson; Nour Eddine Fahmi; Kenneth Alibek; Sidney M Hecht
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2005-09-19
Journal Detail:
Title:  Bioorganic & medicinal chemistry     Volume:  14     ISSN:  0968-0896     ISO Abbreviation:  Bioorg. Med. Chem.     Publication Date:  2006 Jan 
Date Detail:
Created Date:  2005-11-21     Completed Date:  2006-05-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9413298     Medline TA:  Bioorg Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  33-40     Citation Subset:  IM    
Affiliation:
Innovative Biologics, Inc., 10900 University Blvd., Manassas, VA 20110, USA. vak@innovbio.com
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, Bacterial
Bacterial Toxins / antagonists & inhibitors*
Cell Line
Mice
beta-Cyclodextrins / chemistry,  pharmacology*
Grant Support
ID/Acronym/Agency:
1R43AI052894-01/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Bacterial; 0/Bacterial Toxins; 0/anthrax toxin; 0/beta-Cyclodextrins; 7585-39-9/betadex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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