Praziquantel analogs with activity against juvenile Schistosoma mansoni

Yuxiang Dong, Jacques Chollet, Mireille Vargas, Nuha R. Mansour, Quentin Bickle, Yazen Alnouti, Jiangeng Huang, Jennifer Keiser, Jonathan L Vennerstrom

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Six amide and four urea derivatives of praziquantel were synthesized and tested for antischistosomal activity against juvenile and adults stages of Schistosoma mansoni in infected mice. Only one of these had significant activity against adult worms, but, unlike praziquantel, six of these had low to modest activity against juvenile worms. A praziquantel ketone derivative had the best combination of activity against juveniles and adults, but it had no effect on the motility of adult S. mansoni in ex vivo culture. Cytochrome P450 metabolic stability data support the hypothesis that the major trans-cyclohexanol metabolite of praziquantel plays an important role in the antischistosomal activity of this drug.

Original languageEnglish (US)
Pages (from-to)2481-2484
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number8
DOIs
StatePublished - Apr 15 2010

Fingerprint

Praziquantel
Schistosoma mansoni
Cyclohexanols
Derivatives
Metabolites
Ketones
Amides
Cytochrome P-450 Enzyme System
Urea
Pharmaceutical Preparations

Keywords

  • Antischistosomal
  • Praziquantel
  • Schistosoma mansoni

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Praziquantel analogs with activity against juvenile Schistosoma mansoni. / Dong, Yuxiang; Chollet, Jacques; Vargas, Mireille; Mansour, Nuha R.; Bickle, Quentin; Alnouti, Yazen; Huang, Jiangeng; Keiser, Jennifer; Vennerstrom, Jonathan L.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 20, No. 8, 15.04.2010, p. 2481-2484.

Research output: Contribution to journalArticle

Dong, Yuxiang ; Chollet, Jacques ; Vargas, Mireille ; Mansour, Nuha R. ; Bickle, Quentin ; Alnouti, Yazen ; Huang, Jiangeng ; Keiser, Jennifer ; Vennerstrom, Jonathan L. / Praziquantel analogs with activity against juvenile Schistosoma mansoni. In: Bioorganic and Medicinal Chemistry Letters. 2010 ; Vol. 20, No. 8. pp. 2481-2484.
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