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

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...

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Autores principales: Soleilhac, Emmanuelle, Brillet-Guéguen, Loraine, Roussel, Véronique, Prudent, Renaud, Touquet, Bastien, Dass, Sheena, Aci-Sèche, Samia, Kasam, Vinod, Barette, Caroline, Imberty, Anne, Breton, Vincent, Vantard, Marylin, Horvath, Dragos, Botté, Cyrille, Tardieux, Isabelle, Roy, Sylvaine, Maréchal, Eric, Lafanechère, Laurence
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213459/
https://www.ncbi.nlm.nih.gov/pubmed/30304836
http://dx.doi.org/10.3390/ijms19103085
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author Soleilhac, Emmanuelle
Brillet-Guéguen, Loraine
Roussel, Véronique
Prudent, Renaud
Touquet, Bastien
Dass, Sheena
Aci-Sèche, Samia
Kasam, Vinod
Barette, Caroline
Imberty, Anne
Breton, Vincent
Vantard, Marylin
Horvath, Dragos
Botté, Cyrille
Tardieux, Isabelle
Roy, Sylvaine
Maréchal, Eric
Lafanechère, Laurence
author_facet Soleilhac, Emmanuelle
Brillet-Guéguen, Loraine
Roussel, Véronique
Prudent, Renaud
Touquet, Bastien
Dass, Sheena
Aci-Sèche, Samia
Kasam, Vinod
Barette, Caroline
Imberty, Anne
Breton, Vincent
Vantard, Marylin
Horvath, Dragos
Botté, Cyrille
Tardieux, Isabelle
Roy, Sylvaine
Maréchal, Eric
Lafanechère, Laurence
author_sort Soleilhac, Emmanuelle
collection PubMed
description 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.
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spelling pubmed-62134592018-11-14 Specific Targeting of Plant and Apicomplexa Parasite Tubulin through Differential Screening Using In Silico and Assay-Based Approaches Soleilhac, Emmanuelle Brillet-Guéguen, Loraine Roussel, Véronique Prudent, Renaud Touquet, Bastien Dass, Sheena Aci-Sèche, Samia Kasam, Vinod Barette, Caroline Imberty, Anne Breton, Vincent Vantard, Marylin Horvath, Dragos Botté, Cyrille Tardieux, Isabelle Roy, Sylvaine Maréchal, Eric Lafanechère, Laurence Int J Mol Sci Article 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. MDPI 2018-10-09 /pmc/articles/PMC6213459/ /pubmed/30304836 http://dx.doi.org/10.3390/ijms19103085 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Soleilhac, Emmanuelle
Brillet-Guéguen, Loraine
Roussel, Véronique
Prudent, Renaud
Touquet, Bastien
Dass, Sheena
Aci-Sèche, Samia
Kasam, Vinod
Barette, Caroline
Imberty, Anne
Breton, Vincent
Vantard, Marylin
Horvath, Dragos
Botté, Cyrille
Tardieux, Isabelle
Roy, Sylvaine
Maréchal, Eric
Lafanechère, Laurence
Specific Targeting of Plant and Apicomplexa Parasite Tubulin through Differential Screening Using In Silico and Assay-Based Approaches
title Specific Targeting of Plant and Apicomplexa Parasite Tubulin through Differential Screening Using In Silico and Assay-Based Approaches
title_full Specific Targeting of Plant and Apicomplexa Parasite Tubulin through Differential Screening Using In Silico and Assay-Based Approaches
title_fullStr Specific Targeting of Plant and Apicomplexa Parasite Tubulin through Differential Screening Using In Silico and Assay-Based Approaches
title_full_unstemmed Specific Targeting of Plant and Apicomplexa Parasite Tubulin through Differential Screening Using In Silico and Assay-Based Approaches
title_short Specific Targeting of Plant and Apicomplexa Parasite Tubulin through Differential Screening Using In Silico and Assay-Based Approaches
title_sort specific targeting of plant and apicomplexa parasite tubulin through differential screening using in silico and assay-based approaches
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6213459/
https://www.ncbi.nlm.nih.gov/pubmed/30304836
http://dx.doi.org/10.3390/ijms19103085
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