%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Loeuillet, C.
%A Touquet, B.
%A Oury, Bruno
%A Eddaikra, N.
%A Pons, J. L.
%A Guichou, J. F.
%A Labesse, G.
%A Sereno, Denis
%T Synthesis of aminophenylhydroxamate and aminobenzylhydroxamate derivatives and in vitro screening for antiparasitic and histone deacetylase inhibitory activity
%D 2018
%L fdi:010072672
%G ENG
%J International Journal for Parasitology : Drugs and Drug Resistance
%@ 2211-3207
%M ISI:000428405000008
%N 1
%P 59-66
%R 10.1016/j.ijpddr.2018.01.002
%U https://www.documentation.ird.fr/hor/fdi:010072672
%> https://horizon.documentation.ird.fr/exl-doc/pleins_textes/divers18-04/010072672.pdf
%V 8
%W Horizon (IRD)
%X 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 mu M) that contrast with the highly efficient anti-Toxoplasma activity (IC50 < 1.0 mu M) 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 mu M) a moderate cytotoxicity and a high anti-Toxoplasma activity in the range of known anti-Toxoplasma compounds (IC50 of 0.35-2.25 mu M). 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.
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