Synthesis of (aryloxyacetylamino)-isonicotinic/nicotinic acid analogues as potent hypoxia-inducible factor (HIF)-1α inhibitors

Shanthaveerappa K. Boovanahalli, Xuejun Jin, Yinglan Jin, Jin Hwan Kim, Nguyen Tien Dat, Young Soo Hong, Jeong Hyung Lee, Sang Hun Jung, Kyeong Lee, Jung Joon Lee

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32 Scopus citations

Abstract

We report a new series of HIF-1α inhibitors which were obtained through structural modifications of previously reported lead 1. The in vitro inhibitory potencies of newly synthesized compounds were evaluated against hypoxia-induced HIF-1 activation using cell-based reporter assay in three human cancer cell lines including SK-Hep-1, Hep3B, and AGS cells. Several compounds displayed significant inhibitory activity in all the three tested cell lines. In particular, analogue 17 displayed potent inhibition of hypoxia-induced accumulation of HIF-1α protein in Hep3B cell line, in addition to the dose-dependent inhibition of HIF-1 target genes VEGF and EPO.

Original languageEnglish
Pages (from-to)6305-6310
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume17
Issue number22
DOIs
StatePublished - 15 Nov 2007

Keywords

  • HIF-1
  • HIF-inhibitor
  • Hypoxia
  • Hypoxia-inducible factor
  • Isonicotinic/nicotinic acid analogues

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