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

doi:10.1016/j.bmcl.2010.03.001

Praziquantel analogs with activity against juvenile Schistosoma mansoni

Bioorg Med Chem Lett. 2010 Apr 15;20(8):2481-4. doi: 10.1016/j.bmcl.2010.03.001. Epub 2010 Mar 4.

Authors

Yuxiang Dong¹, Jacques Chollet, Mireille Vargas, Nuha R Mansour, Quentin Bickle, Yazen Alnouti, Jiangeng Huang, Jennifer Keiser, Jonathan L Vennerstrom

Affiliation

¹ University of Nebraska Medical Center, College of Pharmacy, Omaha, NE, USA.

PMID: 20303754
DOI: 10.1016/j.bmcl.2010.03.001

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anthelmintics / pharmacology*
Mice
Praziquantel / pharmacology*
Schistosoma mansoni / drug effects*

Substances

Anthelmintics
Praziquantel