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 (<b>1</b>–<b>6</b>) and five previously reported (<b>7</b>–<b>11</b>) sesterterpene analogues and two unrelated sesterterpenes. Two new sesterterpenes, thorectidaeolide A (<b>1</b>) and 4-acetoxythorectidaeolide A (<b>2</b>), and luffariellolide (<b>11</b>) 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 (<b>11</b>) exhibited a significant level of cytotoxicity that mirrored its HIF-1 inhibitory activity. Neither compound <b>1</b>, compound <b>2</b>, nor any of the other less active sesterterpenes suppressed breast tumor T47D or MDA-MB-231 cell viability