Journal
CHEMMEDCHEM
Volume 8, Issue 2, Pages 265-271Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cmdc.201200502
Keywords
angiogenesis; carboranes; HIF-1; manassantins; transcriptional activity
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology, Japan
Ask authors/readers for more resources
Diaromatic-substituted ortho- and meta-carboranes were synthesized as mimics of manassantin A. Among the carboranes synthesized, compounds 1 and 2 showed significant inhibition of hypoxia-induced HIF-1 transcriptional activity, with IC50 values of 3.2 and 2.2 mu M, respectively. Compounds 1 and 2 similarly suppressed hypoxia-induced HIF-1a accumulation in a concentration-dependent manner without affecting the expression level of HIF-1a mRNA. The hypoxia-induced accumulation and translocation of HIF-1a into nuclei were not observed in HeLa cells treated with compounds 1 and 2 by immunofluorescence analysis, revealing that the inhibition of hypoxia-induced HIF-1 transcriptional activity is induced by compounds 1 and 2 through a degradation pathway of the HIF-1a protein under hypoxic conditions.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available