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

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 MT 1 and MT 2 receptors with EC 50 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 MT 2 receptor by bonding to Phe 118, Gly 121, His 208, Try 294 and Ala 297 residues.