RESUMO
Chromatographic fractionation of the EtOH extracts of the Traditional Chinese Medicine (TCM) Chloranthus japonicus, has led to the isolation of a new lindenane-type sesquiterpenoid lactone derivative (1). Rosmarylchloranthalactone E (1), which consists of lindenane sesquiterpenoid lactone and rosmarinic acid moieties linked via an ester bridge, was structurally elucidated by 1D and 2D NMR and HRMS data. Compound 1 was a potent phosphodiesterase-4 (PDE4) inhibitor with an IC50 value of 0.96 ± 0.04 µM.
Assuntos
Lactonas/isolamento & purificação , Magnoliopsida/química , Inibidores da Fosfodiesterase 4/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Lactonas/farmacologia , Espectroscopia de Ressonância Magnética , Inibidores da Fosfodiesterase 4/química , Inibidores da Fosfodiesterase 4/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
The bioassay-guided phytochemical study of a traditional Chinese medicine Morus alba led to the isolation of 18 prenylated flavonoids (1-18), of which (±)-cyclomorusin (1/2), a pair of enantiomers, and 14-methoxy-dihydromorusin (3) are the new ones. Subsequent structural modification of the selected components by methylation, esterification, hydrogenation, and oxidative cyclization led to 14 more derivatives (19-32). The small library was screened for its inhibition against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Among them, nine compounds (1-5, 8, 10, 16, and 17) exhibited remarkable activities with IC50 values ranging from 0.0054 to 0.40⯵M, being more active than the positive control rolipram (IC50 = 0.62 µM). (+)-Cyclomorusin (1), the most active natural PDE4 inhibitor reported so far, also showed a high selectivity across other PDE members with the selective fold greater than 55. The SAR study revealed that the presence of prenyls at C-3 and/or C-8, 2H-pyran ring D, and the phenolic hydroxyl groups were important to the activity, which was further supported by the recognition mechanism study of the inhibitors with PDE4 by using molecular modeling.
Assuntos
Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Flavonoides/farmacologia , Morus/química , Inibidores da Fosfodiesterase 4/farmacologia , Relação Dose-Resposta a Droga , Flavonoides/química , Flavonoides/isolamento & purificação , Humanos , Modelos Moleculares , Estrutura Molecular , Inibidores da Fosfodiesterase 4/química , Inibidores da Fosfodiesterase 4/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Eight new lindenane sesquiterpenoid dimers, chlojapolides A-H (1-8), along with 11 known analogues were isolated from the whole plant of Chloranthus japonicus. Their structures including absolute configurations were elucidated by spectral and chemical methods. All the compounds were examined for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages, and compounds 1, 11, 13, and 17 exhibited pronounced inhibition with IC50 values in the range of 6.91-15.75µM, being more active than the positive control, quercetin (IC50=15.90µM).
Assuntos
Produtos Biológicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Magnoliopsida/química , Óxido Nítrico/antagonistas & inibidores , Sesquiterpenos/farmacologia , Animais , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Linhagem Celular , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Óxido Nítrico/biossíntese , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
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.
Assuntos
Anti-Inflamatórios/farmacologia , Crotalaria/química , Isoflavonas/farmacologia , Inibidores da Fosfodiesterase 4/farmacologia , Extratos Vegetais/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Concentração Inibidora 50 , Isoflavonas/química , Isoflavonas/isolamento & purificação , Medicina Tradicional Chinesa , Simulação de Dinâmica Molecular , Estrutura Molecular , Inibidores da Fosfodiesterase 4/química , Inibidores da Fosfodiesterase 4/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Relação Estrutura-AtividadeRESUMO
A new apotirucallane-type triterpenoid with an unusual 22,23-epoxy group in the side chain, 22,23-epoxy-apotirucalla-14-ene-3alpha,7alpha,24alpha,25-tetraol (1), was isolated from the leaves and twigs of Orophea yunnanensis. The structure of 1 was established on the basis of HRESIMS, 1D, and 2D NMR spectroscopic methods. This is the first phytochemical study of Orophea yunnanensis, and the biogenetic origin of 1 was postulated. Compound 1 exhibited weak cytotoxicity in vitro against the growth of CNE1 nasopharyngeal carcinoma cell line with an IC50 value of 9.7 microg/mL.