6SBR

The crystal structure of PfA-M1 in complex with 7-amino-1,4-dibromo-5,7,8,9-tetrahydrobenzocyclohepten-6-one

Summary for 6SBR

• Entry DOI: 10.2210/pdb6sbr/pdb
• Descriptor: M1-family alanyl aminopeptidase, ZINC ION, [(7~{S})-1,4-bis(bromanyl)-6,6-bis(oxidanyl)-5,7,8,9-tetrahydrobenzo[7]annulen-7-yl]azanium, ... (7 entities in total)
• Functional Keywords: m1 aminopeptidase, hydrolase
• Biological source: Plasmodium falciparum (isolate 3D7)
• Total number of polymer chains: 1
• Total formula weight: 108445.09

Authors

Salomon, E.,Schmitt, M.,Mouray, E.,McEwen, A.G.,Torchy, M.,Poussin-Courmontagne, P.,Alavi, S.,Tarnus, C.,Cavarelli, J.,Florent, I.,Albrecht, S. (deposition date: 2019-07-22, release date: 2020-03-25, Last modification date: 2024-01-24)

Primary citation

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.
Aminobenzosuberone derivatives as PfA-M1 inhibitors: Molecular recognition and antiplasmodial evaluation.
Bioorg.Chem., 98:103750-103750, 2020

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 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.

PubMed: 32182520
DOI: 10.1016/j.bioorg.2020.103750

Experimental method

X-RAY DIFFRACTION (1.54 Å)