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 language | English |
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Pages (from-to) | 6305-6310 |
Number of pages | 6 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 17 |
Issue number | 22 |
DOIs | |
State | Published - 15 Nov 2007 |
Keywords
- HIF-1
- HIF-inhibitor
- Hypoxia
- Hypoxia-inducible factor
- Isonicotinic/nicotinic acid analogues