Competitive neutrophil elastase inhibitory isoflavones from the roots of Flemingia philippinensis.
Bioorg Chem
; 78: 249-257, 2018 08.
Article
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| MEDLINE
| ID: mdl-29614436
Flemingia philippinensis has been used throughout history to cure rheumatism associated with neutrophil elastase (NE). In this study, we isolated sixteen NE inhibitory flavonoids (1-16), including the most potent and abundant prenyl isoflavones (1-9), from the F. philippinensis plant. These prenyl isoflavones (2, 3, 5, 7, and 9) competitively inhibited NE, with IC50 values of 1.3-12.0⯵M. In addition, they were reversible, simple, slow-binding inhibitors according to their respective parameters. Representative compound 3 had an IC50â¯=â¯1.3⯵M, k3â¯=â¯0.04172⯵M-1â¯min-1, k4â¯=â¯0.0064â¯min-1, and Kiappâ¯=â¯0.1534⯵M. The Kik/Kiv ratios (18.5â¯â¼â¯24.6) for compound 3 were consistent with typical competitive inhibitors. The prenyl functionality of isoflavones significantly affected inhibitory potencies and mechanistic behavior by shifting the competitive mode to a noncompetitive one. The remaining flavonoids (10-16) were confirmed as mixed type I inhibitors that preferred to bind free enzyme rather than the enzyme-substrate complex. Fluorescence quenching analyses indicated that the inhibitory potency (IC50) closely followed the binding affinity (KSV).
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Raíces de Plantas
/
Elastasa de Leucocito
/
Isoflavonas
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Fabaceae
Límite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Año:
2018
Tipo del documento:
Article
Pais de publicación:
Estados Unidos