Polybenzyls from Gastrodia elata, their agonistic effects on melatonin receptors and structure-activity relationships

Bioorg Med Chem. 2019 Aug 1;27(15):3299-3306. doi: 10.1016/j.bmc.2019.06.008. Epub 2019 Jun 6.

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 μM. 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.

Keywords: Docking study; Gastrodia elata; Melatonin receptors; Polybenzyls; Structure-activity relationships.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / isolation & purification
  • Drugs, Chinese Herbal / pharmacology*
  • Gastrodia / chemistry*
  • HEK293 Cells
  • Humans
  • Medicine, Chinese Traditional
  • Molecular Docking Simulation
  • Molecular Structure
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Receptors, Melatonin / agonists*
  • Structure-Activity Relationship

Substances

  • Drugs, Chinese Herbal
  • Plant Extracts
  • Receptors, Melatonin