Structures and Potential Antitumor Activity of Sesterterpenes from the Marine Sponge Hyrtios communis (Carter 1885)

摘要

The extract of marine sponge Hyrtios communis (Carter, 1885) (Order Dictyoceratida, Family Thorectidae) 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 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 >1, nor >2, or any of the other less active sesterterpenes suppressed breast tumor T47D or MDA-MB-231 cell viability.