Structures and potential antitumor activity of sesterterpenes from the marine sponge Hyrtios communis
- J Nat Prod. 2013 Aug 23;76(8):1492-7. doi: 10.1021/np400350k.
- 1. Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, Mississippi 38677, USA.
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.