Next Article in Journal
New Cytokines in the Pathogenesis of Atopic Dermatitis—New Therapeutic Targets
Previous Article in Journal
Cigarette Smoke During Breastfeeding in Rats Changes Glucocorticoid and Vitamin D Status in Obese Adult Offspring
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2018, 19(10), 3085; https://doi.org/10.3390/ijms19103085

Specific Targeting of Plant and Apicomplexa Parasite Tubulin through Differential Screening Using In Silico and Assay-Based Approaches

1
Institut de Biosciences et Biotechnologies de Grenoble (BIG), Université Grenoble Alpes, CEA, INSERM, BGE U1038, CEA-Grenoble, 17 rue des Martyrs, 38000 Grenoble, France
2
Sorbonne Université, CNRS, Integrative Biology of Marine Models (LBI2M), Station Biologique de Roscoff (SBR), 29680 Roscoff, France
3
Laboratoire de Physiologie Cellulaire Végétale, Unité Mixte de Recherches 5168 CNRS, CEA, INRA, Institut de Biosciences et Biotechnologies de Grenoble (BIG), Université Grenoble Alpes, CEA-Grenoble, 17 rue des Martyrs, 38000 Grenoble, France
4
Institute for Advanced Biosciences (IAB), Team Regulation and Pharmacology of the Cytoskeleton, INSERM U1209, CNRS UMR5309, Université Grenoble Alpes, 38000 Grenoble, France
5
Institute for Advanced Biosciences (IAB), Team Membrane and Cell Dynamics of Host Parasite Interactions, INSERM U1209, CNRS UMR5309, Université Grenoble Alpes, 38000 Grenoble, France
6
Institute for Advanced Biosciences (IAB), Team ApicoLipid, CNRS UMR5309, Université Grenoble Alpes, INSERM U1209, 38000 Grenoble, France
7
Institut de Chimie Organique et Analytique (ICOA), UMR7311 CNRS-Université d’Orléans, Université d’Orléans, 45067 Orléans CEDEX 2, France
8
Laboratoire de Physique de Clermont, Université Clermont Auvergne, CNRS/IN2P3, UMR6533, 4 Avenue Blaise Pascal TSA 60026, CS 60026 63178 Aubière CEDEX, France
9
Centre de Recherche sur les Macromolécules Végétales, Université Grenoble Alpes, CNRS, 38000 Grenoble, France
10
Grenoble Institut des Neurosciences; Inserm U1216; Université Grenoble Alpes, 38000 Grenoble, France
11
Laboratoire de Chemoinformatique, UMR7140 CNRS—Université de Strasbourg, 4 rue Blaise Pascal, 67000 Strasbourg, France
*
Authors to whom correspondence should be addressed.
Received: 6 September 2018 / Revised: 2 October 2018 / Accepted: 4 October 2018 / Published: 9 October 2018
(This article belongs to the Section Molecular Plant Sciences)
Full-Text   |   PDF [3259 KB, uploaded 9 October 2018]   |  

Abstract

Dinitroanilines are chemical compounds with high selectivity for plant cell α-tubulin in which they promote microtubule depolymerization. They target α-tubulin regions that have diverged over evolution and show no effect on non-photosynthetic eukaryotes. Hence, they have been used as herbicides over decades. Interestingly, dinitroanilines proved active on microtubules of eukaryotes deriving from photosynthetic ancestors such as Toxoplasma gondii and Plasmodium falciparum, which are responsible for toxoplasmosis and malaria, respectively. By combining differential in silico screening of virtual chemical libraries on Arabidopsis thaliana and mammal tubulin structural models together with cell-based screening of chemical libraries, we have identified dinitroaniline related and non-related compounds. They inhibit plant, but not mammalian tubulin assembly in vitro, and accordingly arrest A. thaliana development. In addition, these compounds exhibit a moderate cytotoxic activity towards T. gondii and P. falciparum. These results highlight the potential of novel herbicidal scaffolds in the design of urgently needed anti-parasitic drugs. View Full-Text
Keywords: Tubulin; dinitroanilines; plant cells; Toxoplasma gondii; Plasmodium falciparum; virtual screening; small molecules; cell-based assays Tubulin; dinitroanilines; plant cells; Toxoplasma gondii; Plasmodium falciparum; virtual screening; small molecules; cell-based assays
Figures

Figure 1

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

Soleilhac, E.; Brillet-Guéguen, L.; Roussel, V.; Prudent, R.; Touquet, B.; Dass, S.; Aci-Sèche, S.; Kasam, V.; Barette, C.; Imberty, A.; Breton, V.; Vantard, M.; Horvath, D.; Botté, C.; Tardieux, I.; Roy, S.; Maréchal, E.; Lafanechère, L. Specific Targeting of Plant and Apicomplexa Parasite Tubulin through Differential Screening Using In Silico and Assay-Based Approaches. Int. J. Mol. Sci. 2018, 19, 3085.

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