Discovery of novel hit compounds with broad activity against visceral and cutaneous Leishmania species by comparative phenotypic screening.

ABSTRACT: The limited success of recent phenotypic anti-leishmanial drug screening campaigns calls for new screening strategies for the discovery of clinically relevant hits. Here we present such a novel strategy based on physiologically relevant, ex vivo biology. We established high content phenotypic assays that combine primary murine macrophages and lesion-derived, virulent L. donovani and L. amazonensis amastigotes, which we applied to validate previously identified, anti-leishmanial hit compounds referred to as 'GSK Leish-Box'. Together with secondary screens using cultured promastigotes, our pipeline distinguished stage- and/or species-specific compounds, including 20 hits with broad activity at 10 µM against intracellular amastigotes of both viscerotropic and dermotropic Leishmania. Even thou

SUBMITTER: Lamotte S 

PROVIDER: S-EPMC6345745 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature