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Design, synthesis and biological evaluation of praziquantel and endoperoxide conjugates as antischistosomal agents. | LitMetric
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.Conclusion : Important preliminary results were obtained from thorough activity evaluation of praziquantel-endoperoxide conjugates. Further pharmacokinetic property investigation is necessary to improve in vivo efficacy.
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