Racemic Bisindole Alkaloids: Structure, Bioactivity, and Computational Study

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 mu mol/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.

Automated summary

The study isolated new racemic and dimeric indole alkaloids from a cultured sponge, with one of the compounds, (+)-spondomine, showing cytotoxicity against K562 cell line and stronger signaling inhibitory activity. All stereoisomers significantly promoted angiogenesis and exhibited moderate anti-inflammatory effects. Quantum chemical calculations and deuteration experiments were used to guide the synthesis of the target compounds.