title: Development of chiral praziquantel analogues as potential drug candidates with activity to juvenile Schistosoma japonicum.
abstract: A series of chiral praziquantel analogues were synthesized and evaluated against Schistosoma japonicum both in vitro and in vivo. All compounds exhibited low to considerable good activity in vivo. Remarkably, worm reduction rate of R-3 was 60.0% at a single oral dose of 200mg/kg against juvenile stage of Schistosoma japonicum. The target compounds displayed in vivo antischistosomal activity against both Schistosoma japonicum and Schistosoma mansoni. Furthermore, all R-isomers displayed stronger antischistosomal activity than S-isomers in vivo, indicating R-isomers were the active enantiomers, while S-isomers were less active ones. This structure activity relationship (SAR) could have important implications in further drug development for schistosomiasis.
authors.affiliation: Marine College, Shandong University at Weihai, No. 180, Wenhua West Road, Weihai 264209, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Parasitology, Medical College of Soochow University, Jiangsu 215123, PR China.
authors.forename: LanLan
authors.initials: L
authors.lastname: Dong
authors.affiliation: Marine College, Shandong University at Weihai, No. 180, Wenhua West Road, Weihai 264209, PR China.
authors.forename: Changyan
authors.initials: C
authors.lastname: Hu
authors.affiliation: Department of Parasitology, Medical College of Soochow University, Jiangsu 215123, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Marine College, Shandong University at Weihai, No. 180, Wenhua West Road, Weihai 264209, PR China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Parasitology, Medical College of Soochow University, Jiangsu 215123, PR China. Electronic address: xiachaoming@suda.edu.cn.
authors.forename: Chaoming
authors.initials: C
authors.lastname: Xia
authors.affiliation: Marine College, Shandong University at Weihai, No. 180, Wenhua West Road, Weihai 264209, PR China. Electronic address: dequn.sun@sdu.edu.cn.
authors.forename: Dequn
authors.initials: D
authors.lastname: Sun
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D011223:Praziquantel / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012549:Schistosoma japonicum / Q000187:drug effects* / Q000254:growth & development; D012550:Schistosoma mansoni / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D011223:Praziquantel
keywords: Antischistosomal; Chiral praziquantel analogues; Schistosoma japonicum