The Anthelmintic Activity of Praziquantel Analogs Correlates with Structure-Activity Relationships at TRPMPZQ Orthologs. ACS Med Chem Lett 2023 Nov 09;14(11):1537-1543
Date
11/16/2023Pubmed ID
37970586Pubmed Central ID
PMC10641913DOI
10.1021/acsmedchemlett.3c00350Scopus ID
2-s2.0-85177728490 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
The anthelmintic drug praziquantel remains a key clinical therapy for treating various diseases caused by parasitic flatworms. The parasite target of praziquantel has remained undefined despite longstanding usage in the clinic, although a candidate ion channel target, named TRPMPZQ, has recently been identified. Intriguingly, certain praziquantel derivatives show different activities against different parasites: for example, some praziquantel analogs are considerably more active against cestodes than against schistosomes. Here we interrogate whether the different activities of praziquantel analogs against different parasites are also reflected by unique structure-activity relationships at the TRPMPZQ channels found in these different organisms. To do this, several praziquantel analogs were synthesized and functionally profiled against schistosome and cestode TRPMPZQ channels. Data demonstrate that structure-activity relationships are closely mirrored between parasites and their TRPMPZQ orthologs, providing further support for TRPMPZQ as the therapeutically relevant target of praziquantel.
Author List
Sprague DJ, Kaethner M, Park SK, Rohr CM, Harris JL, Maillard D, Spangenberg T, Lundström-Stadelmann B, Marchant JSAuthors
Jonathan S. Marchant PhD Chair, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinSang Kyu Park PhD Research Scientist I in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Daniel J. Sprague PhD Postdoctoral Fellow in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
