Faculty Collaboration Database

The Anthelmintic Activity of Praziquantel Analogs Correlates with Structure-Activity Relationships at TRPM_PZQ Orthologs. ACS Med Chem Lett 2023 Nov 09;14(11):1537-1543

Date

11/16/2023

Pubmed ID

37970586

Pubmed Central ID

PMC10641913

DOI

10.1021/acsmedchemlett.3c00350

Scopus ID

2-s2.0-85177728490 (requires institutional sign-in at Scopus site)   4 Citations

Abstract

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 TRPM_PZQ, 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 TRPM_PZQ channels found in these different organisms. To do this, several praziquantel analogs were synthesized and functionally profiled against schistosome and cestode TRPM_PZQ channels. Data demonstrate that structure-activity relationships are closely mirrored between parasites and their TRPM_PZQ orthologs, providing further support for TRPM_PZQ 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 JS

Authors

Jonathan S. Marchant PhD Chair, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
Sang Kyu Park PhD Research Scientist I in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin