Bufotenine and its derivatives: synthesis, analgesic effects identification and computational target prediction

Natural product bufotenine (5) which could be isolated from Venenum Bufonis, has been widely used as a tool in central nervous system (CNS) studies. We present here its quaternary ammonium salt (6) which was synthesized with high yields using 5-benzyloxyindole as raw materials, and we firstly discover its analgesic effects in vivo. The analgesic evaluation showed that compounds 5 and 6 had stronger effects on the behavior of formalin induced pain in mice. Moreover, the combination of compound 6 and morphine has a synergistic effect. We intended to explain the molecular mechanism of this effect. Therefore, 36 analgesic-related targets (including 15 G protein-coupled receptors, 6 enzymes, 13 ion channels, and 2 others) were systemically evaluated using reverse docking. The results indicate that bufotenine and its derivatives are closely related to acetyl cholinesterase (AChE) or alpha(4)beta(2) nicotinic acetylcholine receptor (nAChR). This study provides practitioners a new insight of analgesic effects.

Automated summary

Inspired by bufotenine and its derivatives, the quaternary ammonium salt showed analgesic effects and synergistic interactions with morphine. Reverse docking evaluation revealed close relationships with acetyl cholinesterase or nicotinic acetylcholine receptor.