Structures and potential antitumor activity of sesterterpenes from the marine sponge Hyrtios communis.
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.
Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, Mississippi 38677, USA.
Jun
J
Li
Lin
L
Du
Michelle
M
Kelly
Yu-Dong
YD
Zhou
Dale G
DG
Nagle
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors; D020128:Inhibitory Concentration 50; D008386:Marine Biology; D015394:Molecular Structure; D009792:Oceans and Seas; D019029:Palau; D011161:Porifera / Q000737:chemistry*; D054830:Sesterterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013729:Terpenes / Q000494:pharmacology*
C584597:4-acetoxythorectidaeolide A; D000970:Antineoplastic Agents; D051793:Hypoxia-Inducible Factor 1; D054830:Sesterterpenes; D013729:Terpenes; C584598:thorectidaeolide A; C076150:luffariellolide