PMID- 23731014
OWN - NLM
STAT- MEDLINE
DCOM- 20131024
LR  - 20211021
IS  - 1520-6025 (Electronic)
IS  - 0163-3864 (Print)
IS  - 0163-3864 (Linking)
VI  - 76
IP  - 6
DP  - 2013 Jun 28
TI  - Inducers of hypoxic response: marine sesquiterpene quinones activate HIF-1.
PG  - 1175-81
LID - 10.1021/np400320r [doi]
AB  - The hypoxia-inducible factor-1 (HIF-1) transcription factor regulates cellular 
      oxygen homeostasis. Agents that activate HIF-1 and downstream HIF targets 
      represent potential drug leads for the prevention and/or treatment of ischemic 
      disorders. In a search for small-molecule HIF-1 activators, 1936 marine 
      invertebrate and algal extract samples (U.S. National Cancer Institute's Open 
      Repository) were evaluated for HIF-1 activation activity in a cell-based reporter 
      assay. Bioassay-guided fractionation of two active extracts of the sponge 
      Dactylospongia elegans afforded four new sesquiterpene quinones (2-5), one new 
      sesquiterpene phenol (6), the known Golgi disruptor ilimaquinone (1), and three 
      previously reported ilimaquinone analogues (7-9). While antiproliferative 
      activity was observed at higher concentrations, the sesquiterpene quinones (1-3) 
      possessing a 2-hydroxy-5-methoxy-1,4-benzoquinone moiety activated HIF-1 and 
      increased the expression of HIF-1 target gene vascular endothelial growth factor 
      (VEGF) in T47D cells.
FAU - Du, Lin
AU  - Du L
AD  - Department of Pharmacognosy, School of Pharmacy, University of Mississippi, 
      University, Mississippi 38677, USA.
FAU - Zhou, Yu-Dong
AU  - Zhou YD
FAU - Nagle, Dale G
AU  - Nagle DG
LA  - eng
GR  - C06 RR014503/RR/NCRR NIH HHS/United States
GR  - R01 CA098787/CA/NCI NIH HHS/United States
GR  - R56 CA098787/CA/NCI NIH HHS/United States
GR  - CA98787/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130603
PL  - United States
TA  - J Nat Prod
JT  - Journal of natural products
JID - 7906882
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Quinones)
RN  - 0 (Sesquiterpenes)
RN  - 0 (Vascular Endothelial Growth Factor A)
SB  - IM
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Female
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/*drug effects
MH  - Molecular Structure
MH  - Nuclear Magnetic Resonance, Biomolecular
MH  - Oceans and Seas
MH  - Porifera/*chemistry
MH  - Quinones/chemistry/*isolation & purification/*pharmacology
MH  - Sesquiterpenes/chemistry/*isolation & purification/*pharmacology
MH  - Vascular Endothelial Growth Factor A/drug effects
PMC - PMC3718637
MID - NIHMS488443
COIS- The authors declare no competing financial interest.
EDAT- 2013/06/05 06:00
MHDA- 2013/10/25 06:00
PMCR- 2014/06/28
CRDT- 2013/06/05 06:00
PHST- 2013/06/05 06:00 [entrez]
PHST- 2013/06/05 06:00 [pubmed]
PHST- 2013/10/25 06:00 [medline]
PHST- 2014/06/28 00:00 [pmc-release]
AID - 10.1021/np400320r [doi]
PST - ppublish
SO  - J Nat Prod. 2013 Jun 28;76(6):1175-81. doi: 10.1021/np400320r. Epub 2013 Jun 3.