1539276-41-9Relevant articles and documents
Plasmepsin inhibitory activity and structure-guided optimization of a potent hydroxyethylamine-based antimalarial hit
Jaudzems, Kristaps,Tars, Kaspars,Maurops, Gundars,Ivdra, Natalija,Otikovs, Martins,Leitans, Janis,Kanepe-Lapsa, Iveta,Domraceva, Ilona,Mutule, Ilze,Trapencieris, Peteris,Blackman, Michael J.,Jirgensons, Aigars
, p. 373 - 377 (2014/05/06)
Antimalarial hit 1SR (TCMDC-134674) identified in a GlaxoSmithKline cell based screening campaign was evaluated for inhibitory activity against the digestive vacuole plasmepsins (Plm I, II, and IV). It was found to be a potent Plm IV inhibitor with no selectivity over Cathepsin D. A cocrystal structure of 1SR bound to Plm II was solved, providing structural insight for the design of more potent and selective analogues. Structure-guided optimization led to the identification of structurally simplified analogues 17 and 18 as low nanomolar inhibitors of both, plasmepsin Plm IV activity and P. falciparum growth in erythrocytes.