論文

Four unique isoflavone aglycones (barpisoflavone A (1), 2′-hydroxygenistein (2), 5-methylgenistein (3), and gerontoisoflavone A (4)) whose structures were related to genistein were prepared from the tuber of Apios americana Medik. We examined the estrogen receptor and androgen receptor binding activities, estrogen agonistic activities, antioxidant activities, and α-glucosidase inhibitory activities of 1–4. The results obtained showed that 2 possessed potent and 1, 3, and 4 possessed moderate estrogen partial ago- nistic activities, 1 and 2 possessed moderate antioxi- dant activities, and 2 and 3 possessed moderate α-glucosidase inhibitory activities.

Prostate cancer is treated with androgen receptor (AR) antagonists but most patients experience disease pro- gression after long-term treatment with these compounds. Therefore, new AR antagonists are required for patient follow- up treatment. In the course of screening for a new AR antagonist, we isolated the novel compounds antarlides A–E (1–5) from Streptomyces sp. BB47. Antarlides are mutually isomeric with respect to the double bond and have a 22- membered-ring macrocyclic structure. The full stereostructure of 1 was established by chemical modifications, including methanolysis, the Trost method, acetonide formation, and the PGME method. 1–5 inhibited the binding of androgen to ARs in vitro. In addition, 2 inhibited the transcriptional activity of not only wild-type AR but also mutant ARs, which are seen in patients with acquired resistance to clinically used AR antagonists. Therefore, antarlides are a potent new generation of AR antagonists that overcome resistance.