Premium
Racemic Bisindole Alkaloids: Structure, Bioactivity, and Computational Study
Author(s) -
Jin TianYun,
Li PingLin,
Wang CiLi,
Tang XuLi,
Cheng MeiMei,
Zong Yuan,
Luo LianZhong,
Ou HuiLong,
Liu KeChun,
Li GuoQiang
Publication year - 2021
Publication title -
chinese journal of chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.28
H-Index - 41
eISSN - 1614-7065
pISSN - 1001-604X
DOI - 10.1002/cjoc.202100255
Subject(s) - chemistry , indole test , quantum chemical , stereochemistry , cytotoxicity , molecule , organic chemistry , biochemistry , in vitro
Main observation and conclusion The new racemic and dimeric indole alkaloids with the characteristic cyclopenta[ b ]indole backbone, (+)‐ and (–)‐spondomine (1a/1b), were isolated from a cultured sponge Tedania anhelans . A semi‐synthesis was employed to obtain 1a/1b and the other four stereoisomers 1c—1f. Their structures were determined by spectroscopic analysis, single‐crystal X‐ray, and quantum chemical calculations. Six stereoisomers differ in bioactivity according to their absolute configurations. Especially, (+)‐spondomine (1a) displayed cytotoxicity against the K562 cell line and exhibited stronger Wnt and HIF1 dual signaling inhibitory activity at 5 μmol/L than the positive control, which offers an exciting starting point for further investigations. All stereoisomers significantly promoted angiogenesis and showed moderate anti‐inflammation in zebrafish. A quantum chemical calculation and deuteration experiment were applied to unveil the reaction mechanism which guides the synthesis of the target compounds.