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
em 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.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Medicamentos de Ervas Chinesas
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Extratos Vegetais
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Gastrodia
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Receptores de Melatonina
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China