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Ring-truncated deguelin derivatives as potent Hypoxia Inducible Factor-1α (HIF-1α) inhibitors : Ring-truncated deguelin derivatives as potent Hypoxia Inducible Factor-1 alpha (HIF-1 alpha) inhibitors
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Cited 24 time in Scopus
- Authors
- Issue Date
- 2015-11
- Publisher
- Elsevier BV
- Citation
- European Journal of Medicinal Chemistry, Vol.104, pp.157-164
- Abstract
- A series of fluorophenyl and pyridine analogues of 1 and 2 were synthesized as ring-truncated deguelin surrogates and evaluated for their HIF-1 alpha inhibition. Their structure-activity relationship was systematically investigated based on the variation of the linker B-region moiety. Among the inhibitors, compound 25 exhibited potent HIF-1 alpha inhibition in a dose-dependent manner and significant antitumor activity in H1299 with less toxicity than deguelin. It also inhibited in vitro hypoxia-mediated angiogenic processes in HRMECs. The docking study indicates that 25 occupied the C-terminal ATP-binding pocket of HSP90 in a similar mode as 1, which implies that the anticancer and antiangiogenic activities of 25 are derived from HIF-1 alpha destabilization by binding to the C-terminal ATP-binding site of hHSP90. (C) 2015 Elsevier Masson SAS. All rights reserved.
- ISSN
- 0223-5234
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