Target-based discovery of a broad spectrum flukicide.

ABSTRACT: Diseases caused by parasitic flatworms impart a considerable healthcare burden worldwide. Many of these diseases - for example, the parasitic blood fluke infection, schistosomiasis - are treated with the drug praziquantel (PZQ). However, PZQ is ineffective against disease caused by liver flukes from the genus Fasciola. This is due to a single amino acid change within the target of PZQ, a transient receptor potential ion channel (TRPM_PZQ), in Fasciola species. Here we identify benzamidoquinazolinone analogs that are active against Fasciola TRPM_PZQ. Structure-activity studies define an optimized ligand (BZQ) that caused protracted paralysis and damage to the protective tegument of these liver flukes. BZQ also retained activity against Schistosoma

SUBMITTER: Sprague DJ 

PROVIDER: S-EPMC10542552 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature