Meroterpenoids from a Medicinal Fungus Antrodia cinnamomea

Antrodia cinnamomea, a medicinal fungus indigenous to Taiwan, has been shown to exhibit a broad spectrum of bioactivities for the treatments of alcoholic intoxication, diarrhea, abdominal pain, and fatigue, and a number of active principles have been identified. Among the bioactive entities, clinical trials of antroquinonol and 4-acetyl antroquinonol B are being carried out for curing cancer, hypercholesterolemia, and hyperlipidemia. The total synthesis of antroquinonol has been achieved; however, investigating the structure activity relationship of this class of compounds remained difficult due to the tack of available analogues. Twenty antroquinonols isolated from A cinnamomea IFS006 are reported herein. Their structures were elucidated using spectral analysis and by comparison with literature values. Of these, 11 antroquinonol analogues, namely, antroquinonols N-X (1-11), were previously unreported. The growth inhibitory activity of all the antroquinonol analogues was evaluated against human A549 and PC-3 cancer cell lines, and antroquinonol A exhibited the most potent activity, with GI(50) values of 5.7 +/- 0.2 and 13.5 +/- 0.2 mu M, respectively. Antroquinonols V (9) and W (10) also showed growth inhibitory activity against A549 cells with GI(50) values of 8.2 +/- 0.8 and 7.1 +/- 2.1 mu M, respectively, compared to 5-fluorouracil (GI(50) = 4.2 +/- 0.2 mu M).