The Existing Drug Vorinostat as a New Lead Against Cryptosporidiosis by Targeting the Parasite Histone Deacetylases.

ABSTRACT:

Background

Cryptosporidiosis affects all human populations, but can be much more severe or life-threatening in children and individuals with weak or weakened immune systems. However, current options to treat cryptosporidiosis are limited.

Methods

An in vitro phenotypic screening assay was employed to screen 1200 existing drugs for their anticryptosporidial activity and to determine the inhibitory kinetics of top hits. Selected top hits were further evaluated in mice. The action of the lead compound vorinostat on the parasite histone deacetylase (HDAC) was biochemically validated.

Results

Fifteen compounds exhibited anticryptosporidial activity at nanomolar level in vitro. Among them, the histone deacetylase (HDAC) inhibitor vorinostat retained outstanding efficacy in

SUBMITTER: Guo F 

PROVIDER: S-EPMC5939870 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature