Specific Targeting of Plant and Apicomplexa Parasite Tubulin through Differential Screening Using In Silico and Assay-Based Approaches - Plateforme ABiMS
Article Dans Une Revue International Journal of Molecular Sciences Année : 2018

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

Samia Aci-Sèche
Caroline Barette
Vincent Breton
Marylin Vantard
  • Fonction : Auteur
  • PersonId : 846127
Dragos Horvath
Isabelle Tardieux
  • Fonction : Auteur
  • PersonId : 960418

Résumé

Dinitroanilines are chemical compounds with high selectivity for plant cell -tubulin in which they promote microtubule depolymerization. They target -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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hal-02106151 , version 1 (26-05-2020)

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Emmanuelle Soleilhac, Loraine Brillet-Guéguen, Véronique V. Roussel, Renaud Prudent, Bastien Touquet, et al.. Specific Targeting of Plant and Apicomplexa Parasite Tubulin through Differential Screening Using In Silico and Assay-Based Approaches. International Journal of Molecular Sciences, 2018, 19 (10), pp.3085. ⟨10.3390/ijms19103085⟩. ⟨hal-02106151⟩
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