The new racemic and dimeric in dole alkaloids with the characteristic cyclope nta[b]indole backb one,(+)-and(-)-sp on domi ne(la/lb),were isolated from a cultured sponge Tedania anhelans.A semi-synthesis was employed ...The new racemic and dimeric in dole alkaloids with the characteristic cyclope nta[b]indole backb one,(+)-and(-)-sp on domi ne(la/lb),were isolated from a cultured sponge Tedania anhelans.A semi-synthesis was employed to obtain la/lb and the other four stereoisomers lc-If.Their structures were determined by spectroscopic analysis,single-crystal X-ray,and quantum chemical calculations.Six stereoisomers differ in bioactivity according to their absolute con figurations.Especially,(+)-sp on domi ne(la)displayed cytotoxicity against the K562 cell line and exhibited stronger Wnt and HIF1 dual signaling inhibitory activity at 5 pmol/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 reacti on mechanism which guides the synthesis of the target compounds.展开更多
基金supported by the National Natural Science Foundation of China(Nos.41776136,U2006204,2181101213,81991522,and 41876161)the National Key Research and Devel opment Program of China(No.2018YFC0310903)+1 种基金the National Scie nee and Tech no logy Major Project for Sign ifica nt New Drugs Development(No.2018ZX09735-004)the Hainan Province Key Research and Development Plan for Science and Technology Co-operation Projects(No.K33A9002).
文摘The new racemic and dimeric in dole alkaloids with the characteristic cyclope nta[b]indole backb one,(+)-and(-)-sp on domi ne(la/lb),were isolated from a cultured sponge Tedania anhelans.A semi-synthesis was employed to obtain la/lb and the other four stereoisomers lc-If.Their structures were determined by spectroscopic analysis,single-crystal X-ray,and quantum chemical calculations.Six stereoisomers differ in bioactivity according to their absolute con figurations.Especially,(+)-sp on domi ne(la)displayed cytotoxicity against the K562 cell line and exhibited stronger Wnt and HIF1 dual signaling inhibitory activity at 5 pmol/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 reacti on mechanism which guides the synthesis of the target compounds.
