Alice Legru, Fernando A Batista, Anna K Puszko, Anthony Bouillon, Manon Maurel, Mariano Martinez, Abdelaziz Ejjoummany, Laura Ortega Varga, Pauline Adler, Ariel Méchaly, Margot Hadjadj, Piotr Sosnowski, Gérard Hopfgartner, Pedro M Alzari, Arnaud Blondel, Ahmed Haouz, Jean-Christophe Barale, Jean-François Hernandez
Plasmodium multi-resistance, including against artemisinin, seriously threatens malaria treatment and control. Hence, new drugs are urgently needed, ideally targeting different parasitic stages, which are not yet targeted by current drugs. The SUB1 protease is involved in both hepatic and blood stages due to its essential role in the egress of parasites from host cells, and, as potential new target, it would meet the above criteria. We report here the synthesis as well as the biological and structural evaluation of substrate-based α-ketoamide SUB1 pseudopeptidic inhibitors encompassing positions P4-P2'...
March 11, 2024: European Journal of Medicinal Chemistry