Synthesis of fluorescent derivatives of praziquantel: cell-imaging and interaction with Schistosoma japonicum cercariae

• Published in: Organic & biomolecular chemistry 2013-09, Vol.11 (36), p.5989-5993
• Main Authors: Xie, Yunzhi, Li, Yibao, Wu, Yongquan, Liu, Chunhua, Li, Xiaokang, Li, Xun, Fan, Xiaolin
• Format: Article
• Language: English
• Subjects: Animals; Cell Proliferation - drug effects; Cell Survival - drug effects; Cercaria - cytology; Cercaria - drug effects; Dose-Response Relationship, Drug; Fluorescence; HeLa Cells; Humans; Molecular Structure; Praziquantel - chemical synthesis; Praziquantel - chemistry; Praziquantel - pharmacology; Schistosoma japonicum - cytology; Schistosoma japonicum - drug effects; Structure-Activity Relationship
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c3ob41348a

Schistosomiasis is one of the most burdensome of the neglected tropical diseases. Praziquantel is a recommended drug for treatment against all forms of schistosomiasis. To investigate the interaction between praziquantel and Schistosoma japonicum cercariae, two praziquantel derivatives (PZQ-2 and PZQ-3) and one praziquantel fluorescent derivative (PZQ-5) have been synthesized and characterized using nuclear magnetic resonance spectroscopy (NMR) and MS spectra. The cytotoxicity of PZQ-2, PZQ-3 and PZQ-5 was measured by performing the methyl thiazolyl tetrazolium (MTT) assay. The cell viability for them shows that the three compounds exhibit low cytotoxicity to HeLa cells. Cell imaging experiments demonstrate that PZQ-5 is biocompatible and cell-permeable, which indicates that PZQ-5 is suitable for studying their interaction. Confocal fluorescence microscopy revealed that PZQ-5 is mainly located at the cercarial tegument, which leads to the death of cercariae with the increase in time.