Dhananjeyan Mugunthu R, Milev Youli P, Kron Michael A, Nair Muraleedharan G
Bioactive Natural Products and Phytoceuticals, Department of Horticulture and National Food Safety and Toxicology Center, East Lansing, Michigan 48824, USA.
J Med Chem. 2005 Apr 21;48(8):2822-30. doi: 10.1021/jm0492655.
Lymphatic filariasis (elephantiasis) is a global public health problem caused by the parasitic nematodes Wuchereria bancrofti and Brugia malayi. We have previously reported anthraquinones from daylily roots with potent activity against pathogenic trematode Schistosoma mansoni. Here we report the synthesis of novel anthraquinones A-S and their antifilrarial activity. Anthraquinones A-S were synthesized by a single-step Friedel-Crafts acylation reaction between phthalic anhydrides and substituted benzenes. The antifilarial properties of these synthetic anthraquinones were tested against microfilaria as well as adult male and female worms of B. malayi. The most active anthraquinone was K, which showed 100% mortality within 1, 5, and 3 days, respectively, against microfilaria and adult male and female worms at 5 ppm concentration. Albendazole, an oral drug currently used to treat parasitic infections, was used as a positive control. Methylated products of anthraquinones did not affect the microfilaria. Histological examination of treated adult female parasites showed most of the anthraquinones caused marked effects on intrauterine embryos.
淋巴丝虫病(象皮病)是由寄生线虫班氏吴策线虫和马来布鲁线虫引起的全球性公共卫生问题。我们之前报道过黄花菜根中的蒽醌类化合物对致病性吸虫曼氏血吸虫具有强效活性。在此,我们报道新型蒽醌类化合物A - S的合成及其抗丝虫活性。蒽醌类化合物A - S通过邻苯二甲酸酐与取代苯之间的一步傅克酰基化反应合成。这些合成蒽醌类化合物的抗丝虫特性针对马来布鲁线虫的微丝蚴以及成虫雌雄虫进行了测试。活性最强的蒽醌是K,在5 ppm浓度下,分别在1天、5天和3天内对微丝蚴以及成虫雌雄虫显示出100%的死亡率。目前用于治疗寄生虫感染的口服药物阿苯达唑用作阳性对照。蒽醌的甲基化产物对微丝蚴没有影响。对经处理的成年雌性寄生虫进行组织学检查显示,大多数蒽醌对子宫内胚胎有显著影响。