Antiprotozoal activity of dicationic 3,5-diphenylisoxazoles, their prodrugs and aza-analogues
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 2383699
Author(s) Patrick, Donald A.; Bakunov, Stanislav A.; Bakunova, Svetlana M.; Wenzler, Tanja; Brun, Reto; Tidwell, Richard R.
Author(s) at UniBasel Wenzler, Tanja
Brun, Reto
Year 2014
Title Antiprotozoal activity of dicationic 3,5-diphenylisoxazoles, their prodrugs and aza-analogues
Journal Bioorganic & medicinal chemistry
Volume 22
Number 1
Pages / Article-Number 559-576
Keywords Diarylisoxazole, Diamidine, Prodrug, Antiprotozoal, Antitrypanosomal
Abstract Fifty novel prodrugs and aza-analogues of 3,5-bis(4-amidinophenyl)isoxazole and its derivatives were prepared. Eighteen of the 24 aza-analogues exhibited IC₅₀ values below 25 nM against Trypanosoma brucei rhodesiense or Plasmodium falciparum. Six compounds had antitrypanosomal IC₅₀ values below 10 nM. Twelve analogues showed similar antiplasmodial activities, including three with sub-nanomolar potencies. Forty-four diamidines (including 16 aza-analogues) and the 26 prodrugs were evaluated for efficacy in mice infected with T. b. rhodesiense STIB900. Six diamidines cured 4/4 mice at daily 5 mg/kg intraperitoneal doses for 4 days, giving results far superior to pentamidine and furamidine. One prodrug attained 3/4 cures at daily 25 mg/kg oral doses for 4 days.
Publisher Elsevier
ISSN/ISBN 0968-0896
edoc-URL http://edoc.unibas.ch/dok/A6233654
Full Text on edoc No
Digital Object Identifier DOI 10.1016/j.bmc.2013.10.050
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/24268543
Document type (ISI) Article
 
   

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