RESUMEN
A new compound was isolated from the traditional Chinese folk herb Crotalaria ferruginea. The structure of the new compound was identified as (±)-crotaferruphenol (1) based on analyses of its spectroscopic data including NMR, MS, and specific rotation values. (±)-Crotaferruphenol was a novel heterodimer characteristic of a unique spiroketal moiety, which was produced by the condensation reaction of a chromanone and a 2-isopropenybenzofuran. (±)-Crotaferruphenol exhibited inhibitory activity (IC50 = 6.57 µM.) against phosphodiesterase-4 (PDE4), a drug target for the treatment of chronic obstructive pulmonary disease and asthma.
Asunto(s)
Crotalaria/química , Extractos Vegetales/química , Dimerización , Estructura Molecular , Extractos Vegetales/aislamiento & purificaciónRESUMEN
Bioassay-guided fractionation of the ethanol extract of the Chinese folk medicine Crotalaria ferruginea led to the isolation of a new isoflavonoid, 4'-hydroxy-2'-methylalpinum-isoflavone (1), and eight known analogs (2-9). Their structures were elucidated by spectroscopic analysis. Compounds 1, 2, 5, and 8 showed inhibitory activities against phosphodiesterase-4 (PDE4), a therapeutic target of asthma, with IC50 values ranging from 2.57 to 8.94 µM. The possible action mechanism and the structure-activity relationship (SAR) of the active isoflavonoids were explored by using molecular docking and molecular dynamics (MD) simulation methods. Our study herein may explain the anti-inflammatory function of this plant in Chinese folk medicine.
Asunto(s)
Antiinflamatorios/farmacología , Crotalaria/química , Isoflavonas/farmacología , Inhibidores de Fosfodiesterasa 4/farmacología , Extractos Vegetales/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Concentración 50 Inhibidora , Isoflavonas/química , Isoflavonas/aislamiento & purificación , Medicina Tradicional China , Simulación de Dinámica Molecular , Estructura Molecular , Inhibidores de Fosfodiesterasa 4/química , Inhibidores de Fosfodiesterasa 4/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Relación Estructura-ActividadRESUMEN
Six new sesquiterpenoids, aristoyunnolins A-F (1-6), an artifact of isolation [7-O-ethyl madolin W (7)], and 12 known analogues were isolated from stems of Aristolochia yunnanensis. The structures were determined by combined chemical and spectral methods, and the absolute configurations of compounds 2, 3, 5-7, 9, 14, and 17 were determined by the modified Mosher's method and CD analysis. Compounds 1-19 were screened using a bioassay system designed to evaluate the effect on mitogen-activated protein kinases (MAPKs) signaling pathways. Among three MAPKs (ERK1/2, JNK, and p38), compounds 1, 4, 10-13, 16, 18, and 19 exhibited selective inhibition of the phosphorylation of ERK1/2. Compounds 16 and 19 were more active than the positive control PD98059, a known inhibitor of the ERK1/2 signaling pathway.