Antileishmanial Chemotherapy through Clemastine Fumarate Mediated Inhibition of the <i>Leishmania</i> Inositol Phosphorylceramide Synthase.

ABSTRACT: Current chemotherapeutics for leishmaniasis have multiple deficiencies, and there is a need for new safe, efficacious, and affordable medicines. This study describes a successful drug repurposing approach that identifies the over-the-counter antihistamine, clemastine fumarate, as a potential antileishmanial drug candidate. The screening for inhibitors of the sphingolipid synthase (inositol phosphorylceramide synthase, IPCS) afforded, following secondary screening against Leishmania major (Lmj) promastigotes, 16 active compounds. Further refinement through the dose response against LmjIPCS and intramacrophage L. major amastigotes identified clemastine fumarate with good activity and selectivity with respect to the host macrophage. On target engagement was supported by d

SUBMITTER: Mina JGM 

PROVIDER: S-EPMC7802075 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature