Download MendeleyAminobenzosuberone derivatives as PfA-M1 inhibitors: Molecular recognition and antiplasmodial evaluation.
Salomon, E., Schmitt, M., Mouray, E., McEwen, A.G., Bounaadja, L., Torchy, M., Poussin-Courmontagne, P., Alavi, S., Tarnus, C., Cavarelli, J., Florent, I., Albrecht, S.(2020) Bioorg Chem 98: 103750-103750
- PubMed: 32182520
- DOI: https://doi.org/10.1016/j.bioorg.2020.103750
- Primary Citation of Related Structures:
6SBQ, 6SBR - PubMed Abstract:
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 50 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.
Organizational Affiliation:
Université de Haute-Alsace, Université de Strasbourg, CNRS, LIMA UMR 7042, F-68000 Mulhouse, France.
