title: Design, synthesis and biological evaluation of praziquantel and endoperoxide conjugates as antischistosomal agents.
abstract: BACKGROUND
  The widespread use of praziquantel for the treatment of schistosomiasis has led to concerns over the potential development of drug resistance. Therefore, the discovery of novel antischistosomal agents is imperative. In this study, a series of praziquantel and endoperoxide conjugates were synthesized and evaluated as potential antischistosomal agents.
  
  
  RESULTS
  Some compounds exhibited high efficacy against both adult and juvenile Schistosoma, in in vitro studies. Structure-activity relationship (SAR) analysis revealed that compounds with amide bond linker and cyclopentyl adjacent to the 1,2,4,5-tetraxane pharmacophore displayed the highest efficacy. Overall, compounds showed consistent activity against Schistosoma japonicum and Schistosoma mansoni. In vivo study resulted in moderate but statistically significant activity.
  
  
  CONCLUSIONS
  Important preliminary results were obtained from thorough activity evaluation of praziquantel-endoperoxide conjugates. Further pharmacokinetic property investigation is necessary to improve in vivo efficacy.
authors.affiliation: Jiangsu Key Laboratory of Preventive & Translational Medicine for Geriatric Diseases, College of Pharmaceutical Sciences, Soochow University.
authors.forename: Jing-jing
authors.initials: JJ
authors.lastname: Yang
authors.forename: Jerome
authors.initials: J
authors.lastname: Boissier
authors.forename: Jing-Lei
authors.initials: JL
authors.lastname: Chen
authors.forename: Houzong
authors.initials: H
authors.lastname: Yao
authors.forename: Shilin
authors.initials: S
authors.lastname: Yang
authors.forename: Anne
authors.initials: A
authors.lastname: Rognon
authors.forename: Chunhua
authors.initials: C
authors.lastname: Qiao
mesh_terms: D000818:Animals; D015195:Drug Design; D006801:Humans; D051379:Mice; D010545:Peroxides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011223:Praziquantel / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D012549:Schistosoma japonicum / Q000187:drug effects*; D012554:Schistosomiasis japonica / Q000188:drug therapy* / Q000469:parasitology; D012556:Schistosomicides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
chemical_list: D010545:Peroxides; D012556:Schistosomicides; D011223:Praziquantel