Sprague, Daniel J; Kaethner, Marc; Park, Sang-Kyu; Rohr, Claudia M; Harris, Jade L; Maillard, David; Spangenberg, Thomas; Lundström-Stadelmann, Britta; Marchant, Jonathan S (2023). The Anthelmintic Activity of Praziquantel Analogs Correlates with Structure-Activity Relationships at TRPMPZQ Orthologs. ACS medicinal chemistry letters, 14(11), pp. 1537-1543. American Chemical Society 10.1021/acsmedchemlett.3c00350
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sprague-et-al-2023-the-anthelmintic-activity-of-praziquantel-analogs-correlates-with-structure-activity-relationships.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (5MB) | Preview |
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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology 05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Kaethner, Marc Max, Lundström Stadelmann, Britta |
Subjects: |
600 Technology > 630 Agriculture |
ISSN: |
1948-5875 |
Publisher: |
American Chemical Society |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
20 Nov 2023 15:36 |
Last Modified: |
20 Nov 2023 15:45 |
Publisher DOI: |
10.1021/acsmedchemlett.3c00350 |
PubMed ID: |
37970586 |
BORIS DOI: |
10.48350/189034 |
URI: |
https://boris.unibe.ch/id/eprint/189034 |
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