Belofsky Gil, Carreno Roberto, Goswick Shannon M, John David T
Department of Chemistry and Biochemistry, The University of Tulsa, Tulsa, Oklahoma, USA.
Planta Med. 2006 Mar;72(4):383-6. doi: 10.1055/s-2005-916252.
One new and one known isoflavan, 3 S(+)-7-methoxymanuifolin K (1) and manuifolin K (2), respectively, were isolated from methanolic extracts of Dalea aurea (Fabaceae). Isoflavans 1 and 2 exhibited significant in vitro activity against the ameba Naegleria fowleri, an organism responsible for an infrequent but rapidly fatal form of primary amebic meningoencephalitis (PAM). At concentrations of 30 microM, both 1 and 2 caused growth inhibition of N. fowleri at a level comparable to amphotericin B (at 0.1 microM), the currently preferred treatment for this disease. Over a seven-day growth period, 1 and 2 (30 microM) exhibited superior growth inhibition of N. fowleri than amphotericin B after day 4. Isoflavan 2 was evaluated in a mouse model of PAM at a dose of 25 mg/kg/day for five days. While amphotericin B (2.5 mg/kg/day) offered 12.5 % protection of the mice, compound 2 did not protect the mice from PAM infection compared to controls.
从金雀花（豆科）的甲醇提取物中分别分离出一种新的和一种已知的异黄酮，即3 S(+)-7-甲氧基马尼弗林K（1）和马尼弗林K（2）。异黄酮1和2对福氏耐格里阿米巴原虫表现出显著的体外活性，该原虫是一种导致罕见但迅速致命的原发性阿米巴脑膜脑炎（PAM）的病原体。在30微摩尔浓度下，1和2对福氏耐格里阿米巴原虫的生长抑制水平与两性霉素B（0.1微摩尔）相当，两性霉素B是目前治疗该疾病的首选药物。在七天的生长周期中，1和2（30微摩尔）在第4天后对福氏耐格里阿米巴原虫的生长抑制作用优于两性霉素B。异黄酮2在PAM小鼠模型中以25毫克/千克/天的剂量给药五天。虽然两性霉素B（2.5毫克/千克/天）对小鼠提供了12.5%的保护，但与对照组相比，化合物2未能保护小鼠免受PAM感染。
