J. Nat. Prod. 2009, 72, 1927–1936
1927
Lipophilic 2,5-Disubstituted Pyrroles from the Marine Sponge Mycale sp. Inhibit Mitochondrial Respiration and HIF-1 Activation Shui-Chun Mao,† Yang Liu,† J. Brian Morgan,† Mika B. Jekabsons,‡ Yu-Dong Zhou,*,† and Dale G. Nagle*,†,§ Department of Pharmacognosy and Research Institute of Pharmaceutical Sciences, School of Pharmacy, UniVersity of Mississippi, UniVersity, Mississippi 38677, and Department of Biology, UniVersity of Mississippi, UniVersity, Mississippi 38677 ReceiVed July 23, 2009
The lipid extract of the marine sponge Mycale sp. inhibited the activation of hypoxia-inducible factor-1 (HIF-1) in a human breast tumor T47D cell-based reporter assay. Bioassay-guided isolation and structure elucidation yielded 18 new lipophilic 2,5-disubstituted pyrroles and eight structurally related known compounds. The active compounds inhibited hypoxia-induced HIF activation with moderate potency (IC50 values
