Deciphering the mechanism of action of VP343, an antileishmanial drug candidate, in Leishmania infantum.

ABSTRACT: Antileishmanial chemotherapy is currently limited due to severe toxic side effects and drug resistance. Hence, new antileishmanial compounds based on alternative approaches, mainly to avoid the emergence of drug resistance, are needed. The present work aims to decipher the mechanism of action of an antileishmanial drug candidate, named VP343, inhibiting intracellular Leishmania infantum survival via the host cell. Cell imaging showed that VP343 interferes with the fusion of parasitophorous vacuoles and host cell late endosomes and lysosomes, leading to lysosomal cholesterol accumulation and ROS overproduction within host cells. Proteomic analyses showed that VP343 perturbs host cell vesicular trafficking as well as cholesterol synthesis/transport pathways. Furthermore, a knockdown o

SUBMITTER: Obeid S 

PROVIDER: S-EPMC10616420 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature