A synthetic manassantin a derivative inhibits hypoxia-inducible factor 1 and tumor growth

Liwei Lang, Xiaoyu Liu, Yan Li, Qing Zhou, Ping Xie, Chunhong Yan, Xiaoguang Chen

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The dineolignan manassantin A from Saururaceae was recently identified as a hypoxia-inducible factor 1 (HIF-1) inhibitor, but its in-vivo anti-tumor effect has not been explored. We synthesized a series of manassantin A derivatives, and found that replacing the central tetrahydrofuran moiety with a cyclopentane ring yielded a compound (LXY6006) with increased HIF-1-inhibitory activity yet decreased stereochemically complexity amenable to a simplified synthesis scheme. LXY6006 inhibited HIF-1α nuclear accumulation induced by hypoxia, and inhibited cancer cell growth as a consequence of G2/M arrest. Oral administration of LXY6006 significantly inhibited growth of breast, lung, and pancreatic tumors implanted in nude mice. These results indicate that LXY6006 represents a novel class of agents targeting a broad range of human cancers.

Original languageEnglish (US)
Article numbere99584
JournalPloS one
Volume9
Issue number6
DOIs
StatePublished - Jun 12 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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