Aminobenzosuberone derivatives as PfA-M1 inhibitors: Molecular recognition and antiplasmodial evaluation
| Pas de texte intégral | |
|---|---|
| Auteurs |
Emmanuel Salomon Marjorie Schmitt Elisabeth Mouray Alastair Mcewen Lotfi Bounaadja Morgan Torchy Pierre Poussin-courmontagne Sarah Alavi Celine Tarnus Jean Cavarelli Isabelle Florent Sebastien Albrecht |
| Unité de recherche du site |
Laboratoire d'Innovation Moléculaire et Applications - LIMA - UMR7042 Institut de Génétique et de Biologie Moléculaire et Cellulaire - IGBMC - UMR7104 Institut de Génétique et de Biologie Moléculaire et Cellulaire - IGBMC - UMRS964 |
| Langue |
en |
| Volume |
98 |
| Page de début |
103750 |
| Date de première publication |
2020-03-11 |
| Date de parution |
2020-05-01 |
| ISSN |
0045-2068 |
| Titre de la source (revue, livre…) |
Bioorganic Chemistry |
| Résumé |
Aminobenzosuberone-based PfA-M1 inhibitors were explored as novel antimalarial agents against two different Plasmodium falciparum strains. The 4-phenyl derivative 7c exhibited the most encouraging growth inhibitory activity with IC50 values of 6.5-11 Show moreAminobenzosuberone-based PfA-M1 inhibitors were explored as novel antimalarial agents against two different Plasmodium falciparum strains. The 4-phenyl derivative 7c exhibited the most encouraging growth inhibitory activity with IC50 values of 6.5-11.2 µM. X-ray crystal structures and early assessment of DMPK/ADME-Tox parameters allowed us to initiate structure-based drug design approach and understand the liabilities (such as potential metabolic and aqueous solubility issues) as well as identify the opportunities for improvement of this aminobenzosuberone series. It also suggested that compound 7c should be regarded as an attractive chemical tool to investigate the different biological roles of this multifunctional PfA-M1 protein. Show less |
| DOI | 10.1016/j.bioorg.2020.103750 |
| Éditeur |
Elsevier |
| URL éditeur |
https://www.sciencedirect.com/science/article/abs/pii/S0045206819314026?via%3Dihub |
| Titre abrégé de la source |
Bioorganic Chemistry |
| Type de publication |
ACL |
| Topic |
Chimie/Chimie thérapeutique |
| Unité de recherche extérieure au site |
MCAM - Molécules de Communication et Adaptation des Micro-organismes UMR 7245, Muséum National d’Histoire Naturelle, CNRS, Sorbonne Universités, Paris, France |
| Fonction |
aut |
| Identifiant ORCID |
186208723 |
| Identifiant idREF |
124502024 152490817 032175167 113674228 |
| Audience |
International |
| URL | https://univoak.eu/islandora/object/islandora:95726 |