Document Detail


Novel lipophilic acetohydroxamic acid derivatives based on conformationally constrained spiro carbocyclic 2,6-diketopiperazine scaffolds with potent trypanocidal activity.
MedLine Citation:
PMID:  21542562     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We describe novel acetohydroxamic acid derivatives with potent activity against cultured bloodstream-form Trypanosoma brucei and selectivity indices of >1000. These analogues were derived from conformationally constrained, lipophilic, spiro carbocyclic 2,6-diketopiperazine (2,6-DKP) scaffolds by attaching acetohydroxamic acid moieties to the imidic nitrogen. Optimal activity was achieved by placing benzyl groups adjacent to the basic nitrogen of the 2,6-DKP core. S-Enantiomer 7d was the most active derivative against T. brucei (IC(50) = 6.8 nM) and T. cruzi (IC(50) = 0.21 μM).
Authors:
Christos Fytas; Grigoris Zoidis; Nikolaos Tzoutzas; Martin C Taylor; George Fytas; John M Kelly
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-06-27
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  54     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-21     Completed Date:  2011-10-10     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5250-4     Citation Subset:  IM    
Affiliation:
Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, GR-15771, Athens, Greece.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Hydroxamic Acids / chemical synthesis*,  chemistry,  pharmacology
Molecular Conformation
Parasitic Sensitivity Tests
Piperazines / chemical synthesis*,  chemistry,  pharmacology
Rats
Spiro Compounds / chemical synthesis*,  chemistry,  pharmacology
Stereoisomerism
Structure-Activity Relationship
Trypanocidal Agents / chemical synthesis*,  chemistry,  pharmacology
Trypanosoma brucei brucei / drug effects
Trypanosoma cruzi / drug effects
Grant Support
ID/Acronym/Agency:
084175//Wellcome Trust
Chemical
Reg. No./Substance:
0/Hydroxamic Acids; 0/Piperazines; 0/Spiro Compounds; 0/Trypanocidal Agents
Comments/Corrections

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


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