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Design and synthesis of molecular probes for the determination of the target of the anthelmintic drug praziquantel
Affiliation:1. Department of Chemical Biology & Therapeutics, St Jude Children’s Research Hospital, Memphis, TN 38205, USA;2. Department of Biology, University of New Mexico, Albuquerque, NM 87131, USA;1. CCRCB Drug Discovery Group, Centre for Cancer Research and Cell Biology, Queen’s University Belfast, 97 Lisburn Rd., Belfast BT9 7BL, UK;2. Almac Discovery, Almac House, 20 Seagoe Industrial Estate, Craigavon BT63 5QD, UK;3. School of Pharmacy, Queen’s University Belfast, 97 Lisburn Rd., Belfast BT9 7BL, UK;1. Department of Chemistry, ICTM, University of Belgrade, Studentski trg 12-16, 11000 Belgrade, Serbia;2. Institute of Chemistry, University of Graz, NAWI Graz, Heinrichstr. 28, A-8010, Austria;1. Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA;2. Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA;3. Department of Surgery, University of Utah, Salt Lake City, UT 84112, USA;1. School of Inf. and Comp. Science, University of California Irvine, Irvine, CA 92697, USA;2. Computer Science Laboratory, SRI International, Menlo Park, CA 94025, USA;1. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, No. 555 Zu Chong Zhi Road, Shanghai, 201203, China;2. School of Pharmacy, University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, China
Abstract:Schistosomiasis is a highly prevalent neglected tropical disease caused by blood-dwelling helminths of the genus Schistosoma. Praziquantel (PZQ) is the only drug available widely for the treatment of this disease and is administered in racemic form, even though only the (R)-isomer has significant anthelmintic activity. Progress towards the development of a second generation of anthelmintics is hampered by a lack of understanding of the mechanism of action of PZQ. In this Letter, we report an efficient protocol for the small-scale separation of enantiomers of 2 (hydrolyzed PZQ) using supercritical fluid chromatography (SFC). The enantiopure 2 was then used to develop several molecular probes, which can potentially be used to help identify the protein target of PZQ and study its mode of action.
Keywords:Schistosomiasis  Praziquantel  Supercritical fluid chromatography (SFC)  Molecular probes  Anthelmintic
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