2. Academic Validation
  3. Polybenzyls from Gastrodia elata, their agonistic effects on melatonin receptors and structure-activity relationships

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.
Si-Yue Chen 1,  Chang-An Geng 2,  Yun-Bao Ma 2,  Xiao-Yan Huang 2,  Xiao-Tong Yang 1,  Li-Hua Su 1,  Xiao-Feng He 1,  Tian-Ze Li 2,  Zhen-Tao Deng 1,  Zhen Gao 1,  Xue-Mei Zhang 2,  Ji-Jun Chen 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China; Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming 650201, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 2 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China; Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming 650201, China.
  • 3 State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China; Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming 650201, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: chenjj@mail.kib.ac.cn.
PMID: 31204226 DOI: 10.1016/j.bmc.2019.06.008
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.

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