Synthesis of aminophenylhydroxamate and aminobenzylhydroxamate derivatives and in vitro screening for antiparasitic and histone deacetylase inhibitory activity.

ABSTRACT: A series of aminophenylhydroxamates and aminobenzylhydroxamates were synthesized and screened for their antiparasitic activity against Leishmania, Trypanosoma, and Toxoplasma. Their anti-histone deacetylase (HDAC) potency was determined. Moderate to no antileishmanial or antitrypanosomal activity was found (IC₅₀ > 10 μM) that contrast with the highly efficient anti-Toxoplasma activity (IC₅₀ < 1.0 μM) of these compounds. The antiparasitic activity of the synthetized compounds correlates well with their HDAC inhibitory activity. The best-performing compound (named 363) express a high anti-HDAC6 inhibitory activity (IC₅₀ of 0.045 ± 0.015 μM) a moderate cytotoxicity and a high anti-Toxoplasma activity in the range of known anti-Toxoplasma compounds (IC₅₀ of 0.35-2.25 μM). The calculated selectivity index (10-300 using different human cell lines) of the compound 363 makes it a lead compound for the future development of anti-Toxoplasma molecules.

SUBMITTER: Loeuillet C 

PROVIDER: S-EPMC6114082 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature