Design and synthesis of molecular probes for the determination of the target of the anthelmintic drug praziquantel.
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.
Department of Chemical Biology & Therapeutics, St Jude Children's Research Hospital, Memphis, TN 38205, USA.
Lalit Kumar
LK
Sharma
Department of Biology, University of New Mexico, Albuquerque, NM 87131, USA.
Pauline M
PM
Cupit
Department of Chemical Biology & Therapeutics, St Jude Children's Research Hospital, Memphis, TN 38205, USA.
Tino
T
Goronga
Department of Chemical Biology & Therapeutics, St Jude Children's Research Hospital, Memphis, TN 38205, USA.
Thomas R
TR
Webb
Department of Biology, University of New Mexico, Albuquerque, NM 87131, USA. Electronic address: ccunnin@unm.edu.
Charles
C
Cunningham
D000818:Animals; D000871:Anthelmintics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D025924:Chromatography, Supercritical Fluid; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D008297:Male; D008958:Models, Molecular; D015335:Molecular Probes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D058990:Molecular Targeted Therapy; D011223:Praziquantel / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000378:metabolism*; D012555:Schistosomiasis mansoni / Q000188:drug therapy / Q000469:parasitology; D013237:Stereoisomerism; D013379:Substrate Specificity
D000871:Anthelmintics; D015335:Molecular Probes; D011223:Praziquantel
Anthelmintic; Molecular probes; Praziquantel; Schistosomiasis; Supercritical fluid chromatography (SFC)