Polybenzyls from Gastrodia elata, their agonistic effects on melatonin receptors and structure-activity relationships.
Bioorg Med Chem
; 27(15): 3299-3306, 2019 08 01.
Article
en En
| MEDLINE
| ID: mdl-31204226
ABSTRACT
Gastrodia elata is a famous traditional Chinese herb with medicinal and edible application. In this study, nine polybenzyls (1-9), including six new ones (2-5, 7 and 9), were isolated from the EtOAc extract of G. elata. Five compounds 1, 3, 4, 6 and 8 were found to activate melatonin receptors. Especially, compound 1 showed agonistic effects on MT1 and MT2 receptors with EC50 values of 237 and 244⯵M. For better understanding their structure-activity relationships (SARs), ten polybenzyl analogs were further synthesized and assayed for their activities on melatonin receptors. Preliminary SARs study suggested that two para-hydroxy groups were the key pharmacophore for maintaining activity. Molecular docking simulations verified that compound 1 could strongly interact with MT2 receptor by bonding to Phe 118, Gly 121, His 208, Try 294 and Ala 297 residues.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Medicamentos Herbarios Chinos
/
Extractos Vegetales
/
Gastrodia
/
Receptores de Melatonina
Tipo de estudio:
Diagnostic_studies
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
China