Details

Autor(en) / Beteiligte

• Salomon, Emmanuel
• Schmitt, Marjorie
• Mouray, Elisabeth
• McEwen, Alastair G.
• Bounaadja, Lotfi
• Torchy, Morgan
• Poussin-Courmontagne, Pierre
• Alavi, Sarah
• Tarnus, Céline
• Cavarelli, Jean
• Florent, Isabelle
• Albrecht, Sébastien

Titel

Aminobenzosuberone derivatives as PfA-M1 inhibitors: Molecular recognition and antiplasmodial evaluation

Ist Teil von

• Bioorganic chemistry, 2020-05, Vol.98, p.103750, Article 103750

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• [Display omitted] •Antiplasmodial activity of racemic aminobenzosuberone derivatives.•Crystal structure analysis of protein - ligand complexes.•ADME-Tox and pharmacokinetic studies. 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 6.5–11.2 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.