English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/83090
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:
Title

New bis(2-aminoimidazoline) and bisguanidine DNA minor groove binders with potent in vivo antitrypanosomal and antiplasmodial activity

AuthorsRodríguez, F.; Rozas, Isabel; Kaiser, M.; Brun, R.; Nguyen, Binh; Wilson, W. David; García, Rory Nelson; Dardonville, Christophe
Issue Date2008
PublisherAmerican Chemical Society
CitationJournal of Medicinal Chemistry 51: 909- 923 (2008)
AbstractA series of 75 guanidine and 2-aminoimidazoline analogue molecules were assayed in vitro against Trypanosoma brucei rhodesiense STIB900 and Plasmodium falciparum K1. The dicationic diphenyl compounds exhibited the best activities with IC50 values against T. b. rhodesiense and P. falciparum in the nanomolar range. Five compounds (7b, 9a, 9b, 10b, and 14b) cured 100% of treated mice upon ip administration at 20 mg/kg in the difficult to cure T. b. rhodesiense STIB900 mouse model. Overall, the compounds that bear the 2-aminoimidazoline cations benefit from better safety profiles than the guanidine counterparts. The observation of a correlation between DNA binding affinity at AT sites and trypanocidal activity for three series of compounds supported the view of a mechanism of antitrypanosomal action due in part to the formation of a DNA complex. No correlation between antiplasmodial activity and in vitro inhibition of ferriprotoporphyrin IX biomineralisation was observed, suggesting that additional mechanism of action is likely to be involved. © 2008 American Chemical Society.
Publisher version (URL)http://dx.doi.org/10.1021/jm7013088
URIhttp://hdl.handle.net/10261/83090
DOI10.1021/jm7013088
Identifiersdoi: 10.1021/jm7013088
issn: 0022-2623
e-issn: 1520-4804
Appears in Collections:(IQM) Artículos
Files in This Item:
File Description SizeFormat 
Rodriguez et al JMC2008_postprint.pdf485,86 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.