40948-16-1Relevant academic research and scientific papers
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.
New anti-viral drugs for the treatment of the common cold
Maugeri, Caterina,Alisi, Maria A.,Apicella, Claudia,Cellai, Luciano,Dragone, Patrizia,Fioravanzo, Elena,Florio, Saverio,Furlotti, Guido,Mangano, Giorgina,Ombrato, Rosella,Luisi, Renzo,Pompei, Raffaello,Rincicotti, Vito,Russo, Vincenzo,Vitiello, Marco,Cazzolla, Nicola
, p. 3091 - 3107 (2008/09/20)
Human Rhinovirus (HRV) is the most important aetiologic agent of common cold in adults and children. HRV is a single-stranded, positive sense RNA virus and, despite the high level of conservation among different serotypes, sequence alignment of viral protease 3C with mammalian protease reveals no homology. Thus, protease 3C is an optimal target for the development of anti-HRV agents. In the present work we investigated the design, the synthesis and the development of new potential reversible inhibitors against HRV protease 3C. Docking studies on the crystallized structure of HRV2 protease 3C led us to the design and the synthesis of a series of 3,5 disubstituted benzamides able to act as analogues of the substrate. We also developed 1,3,5 trisubstituted benzamides where aromatic substitutions on the aryl ring led us to investigate the importance of π-π interaction on the stabilization of protease 3C-inhibitor complex. All structures were tested for enzymatic inhibition on HRV14 protease 3C. Results highlighted the inhibitory activity of compounds 13, 14, and 20 (91%, 81%, and 85% at 10 μM, respectively), with the latter exhibiting an ID50 (dose that inhibits 50% of the viral cytopathic effect) on HRV-14 = 25 μg/ml.
