Next Article in Journal
Protective Effect of Acteoside on Ovariectomy-Induced Bone Loss in Mice
Previous Article in Journal
The Prediction of Gestational Hypertension, Preeclampsia and Fetal Growth Restriction via the First Trimester Screening of Plasma Exosomal C19MC microRNAs
Previous Article in Special Issue
Cellular Effects of Butyrate on Vascular Smooth Muscle Cells are Mediated through Disparate Actions on Dual Targets, Histone Deacetylase (HDAC) Activity and PI3K/Akt Signaling Network
Open AccessCommunication

A Tiny Change Makes a Big Difference in the Anti-Parasitic Activities of an HDAC Inhibitor

1
Univ Grenoble Alpes, CNRS, CHU Grenoble Alpes, Grenoble INP, TIMC-IMAG, F-38000 Grenoble, France
2
Institute for Advanced Biosciences (IAB), Team Host-Pathogen Interactions & Immunity to Infection, INSERM U 1209, CNRS UMR 5309, Univ Grenoble Alpes, F-38000 Grenoble, France
3
Centre de Biochimie Structurale (CBS), INSERM, CNRS, Univ Montpellier, 34000 Montpellier, France
4
Institute of Research for the Development (IRD), Univ Montpellier, MiVegec, 34000 Montpellier, France
5
Institute of Research for the Development (IRD), Univ Montpellier, InterTryp, 34000 Montpellier, France
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(12), 2973; https://doi.org/10.3390/ijms20122973
Received: 21 May 2019 / Revised: 14 June 2019 / Accepted: 15 June 2019 / Published: 18 June 2019
(This article belongs to the Special Issue Histone Deacetylase Inhibitors in Health and Disease)
  |  
PDF [881 KB, uploaded 18 June 2019]
  |  

Abstract

We previously synthesized an hydroxamate derivative (N-hydroxy-4-[2-(3- methoxyphenyl)acetamido]benzamide) named 363 with potent anti-Toxoplasma gondii activity and histone deacetylase inhibitor (HDACi) effects. Here we show that 1-N-hydroxy-4-N- [(2-methoxyphenyl)methyl]benzene-1,4-dicarboxamide, a 363 isomer, does not have antiparasitic potency and has a 13-fold decrease in HDACi activity. The in silico modeling of T. gondii HDACs of the type II strain discloses identity varying from 25% to 62% on more than 250 residues for S8EP32_TOXG and A0A125YPH4_TOXGM. We observed a high conservation degree with the human HDAC2 (53% and 64% identity, respectively) and a moderate one with the human HDAC8 (30–40%). Two other TgHDACs, S8F6L4_TOXGM and S8GEI3_TOXGM, were identified as displaying a higher similarity with some bacterial orthologs (~35%) than with the human enzymes (~25%). The docking in parallel of the two compounds on the models generated allowed us to gain insights on the docking of these hydroxamate derivatives that guide their specificity and potency against T. gondii histone deacetylase. This information would constitute the rationale from which more specific derivatives can be synthetized. View Full-Text
Keywords: HDACi; Toxoplasma; Hydroxamate; In silico modeling HDACi; Toxoplasma; Hydroxamate; In silico modeling
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Loeuillet, C.; Touquet, B.; Guichou, J.F.; Labesse, G.; Sereno, D. A Tiny Change Makes a Big Difference in the Anti-Parasitic Activities of an HDAC Inhibitor. Int. J. Mol. Sci. 2019, 20, 2973.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top