Issue 83, 2016

Phenanthroindolizidine alkaloids from Tylophora atrofolliculata with hypoxia-inducible factor-1 (HIF-1) inhibitory activity

Abstract

Eleven new alkaloids (1–11), together with eleven known phenanthroindolizidine alkaloids (12–22) were isolated from the whole plants of Tylophora atrofolliculata (Asclepiadaceae). Their structures were characterized by means of NMR spectroscopies including HSQC, HMBC, 1H–1H COSY and NOESY experiments, assisted by high-resolution MS and CD spectral analyses. HIF-1-mediated reporter gene assay in T47D cells was used to evaluate the inhibitory effects of isolated alkaloids on HIF-1 activation. Most alkaloids exhibited extremely potent inhibitory effects with IC50 values in the low nanomolar range. The potency of 14 and 17 are comparable to manassantin B, one of the most potent HIF-1 inhibitors identified so far. Structure–activity relationship (SAR) analyses showed the necessities for high activity, i.e. non-planarity at indolizidine moiety, substitution types and patterns on the phenanthrene and indolizidine moieties. This is the first report on HIF-1 inhibitory activity of phenanthroindolizidine alkaloids, providing a new insight into their underlying anti-cancer mechanism.

Graphical abstract: Phenanthroindolizidine alkaloids from Tylophora atrofolliculata with hypoxia-inducible factor-1 (HIF-1) inhibitory activity

Supplementary files

Article information

Article type
Paper
Submitted
25 Jun 2016
Accepted
11 Aug 2016
First published
23 Aug 2016

RSC Adv., 2016,6, 79958-79967

Phenanthroindolizidine alkaloids from Tylophora atrofolliculata with hypoxia-inducible factor-1 (HIF-1) inhibitory activity

C. Chen, G. Zhu, J. Wang and Z. Jiang, RSC Adv., 2016, 6, 79958 DOI: 10.1039/C6RA16455B

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