Structures and potential antitumor activity of sesterterpenes from the marine sponge Hyrtios communis.

Abstract

The extract of marine sponge Hyrtios communis was found to inhibit activation of the transcription factor hypoxia-inducible factor-1 (HIF-1) in T47D human breast tumor cells. Bioassay-guided isolation led to the identification of six new (1-6) and five previously reported (7-11) sesterterpene analogues and two unrelated sesterterpenes. Two new sesterterpenes, thorectidaeolide A (1) and 4-acetoxythorectidaeolide A (2), and luffariellolide (11) were among the most potent inhibitors of hypoxia (1% O₂)-induced HIF-1 activation (IC₅₀ values of 3.2, 3.5, and 3.6 μM, respectively). Luffariellolide (11) exhibited a significant level of cytotoxicity that mirrored its HIF-1 inhibitory activity. Neither compound 1, compound 2, nor any of the other less active sesterterpenes suppressed breast tumor T47D or MDA-MB-231 cell viability.

• Authors: Jun Li, Lin Du, Michelle Kelly, Yu-Dong Zhou, Dale G Nagle
• Journal: Journal of natural products (J Nat Prod) Vol. 76 Issue 8 Pg. 1492-7 (Aug 23 2013) ISSN: 1520-6025 [Electronic] United States
• PMID: 23944963 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• 4-acetoxythorectidaeolide A
• Antineoplastic Agents
• Hypoxia-Inducible Factor 1
• Sesterterpenes
• Terpenes
• thorectidaeolide A
• luffariellolide

Topics

• Animals
• Antineoplastic Agents (chemistry, isolation & purification, pharmacology)
• Cell Survival (drug effects)
• Drug Screening Assays, Antitumor
• Female
• Humans
• Hypoxia-Inducible Factor 1 (antagonists & inhibitors)
• Inhibitory Concentration 50
• Marine Biology
• Molecular Structure
• Oceans and Seas
• Palau
• Porifera (chemistry)
• Sesterterpenes (chemistry, isolation & purification, pharmacology)
• Terpenes (pharmacology)