| Texto completo | |
| Autor(es): Mostrar menos - |
Lemke, Carina
;
Cianni, Lorenzo
;
Feldmann, Christian
;
Gilberg, Erik
;
Yin, Jiafei
;
Rocho, Fernanda dos Reis
;
de Vita, Daniela
;
Bartz, Ulrike
;
Bajorath, Juergen
;
Montanari, Carlos A.
;
Guetschow, Michael
Número total de Autores: 11
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Bioorganic & Medicinal Chemistry Letters; v. 30, n. 18, p. 6-pg., 2020-09-15. |
| Resumo | |
A library of cathepsin S inhibitors of the dipeptide nitrile chemotype, bearing a bioisosteric sulfonamide moiety, was synthesized. Kinetic investigations were performed at four human cysteine proteases, i.e. cathepsins S, B, K and L. Compound 12 with a terminal 3-biphenyl sulfonamide substituent was the most potent (K-i = 4.02 nM; selectivity ratio cathepsin S/K = 5.8; S/L = 67) and 24 with a 4'-fluoro-4-biphenyl sulfonamide substituent the most selective cathepsin S inhibitor (K-i = 35.5 nM; selectivity ratio cathepsin S/K = 57; S/L = 31). In silico design and biochemical evaluation emphasized the impact of the sulfonamide linkage on selectivity and a possible switch of P2 and P3 substituents with respect to the occupation of the corresponding binding sites of cathepsin S. (AU) | |
| Processo FAPESP: | 13/18009-4 - Planejamento, síntese e atividade tripanossomicida de inibidores covalentes reversíveis da enzima cruzaína |
| Beneficiário: | Carlos Alberto Montanari |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |