Fiche publication
Date publication
mars 2020
Journal
Bioorganic chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CAVARELLI Jean
Tous les auteurs :
Salomon E, Schmitt M, Mouray E, McEwen AG, Bounaadja L, Torchy M, Poussin-Courmontagne P, Alavi S, Tarnus C, Cavarelli J, Florent I, Albrecht S
Lien Pubmed
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 IC 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.
Mots clés
ADMET studies, Aminobenzosuberone inhibitors, Antiplasmodial activity, PfA-M1 aminopeptidase, Protein crystallization
Référence
Bioorg. Chem.. 2020 Mar 11;98:103750
