Strongylophorines: natural product inhibitors of hypoxia-inducible factor-1 transcriptional pathway.
Rapidly increasing experimental and clinical data provides evidence for the role of hypoxia inducible factor-1 (HIF-1) as a crucial mediator of tumor survival and progression. In our effort to identify inhibitors of the HIF-1 activation pathway, we screened fractions from marine invertebrates. Fractions from an extract of Petrosia (Strongylophora) strongylata potently inhibited the HIF-1 activation pathway. Strongylophorines 2, 3, and 8 isolated from the active fractions were found to be responsible for the HIF-1 inhibition with EC 50 values of 8, 13, and 6 microM, respectively.
Mohammed
Kaleem A
KA
Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Jadulco
Raquel C
RC
Bugni
Tim S
TS
Harper
Mary Kay
MK
Sturdy
Megan
M
Ireland
Chris M
CM
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D017930:Genes, Reporter; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors* / Q000235:genetics; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D008156:Luciferases / Q000235:genetics; D047130:Petrosia / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
D000970:Antineoplastic Agents; D004224:Diterpenes; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D008156:Luciferases