A Search for Naturally Occurring Anti-trypanosomal Compounds Using a HeLa Cell Infection Assay System

使用 HeLa 细胞感染检测系统寻找天然存在的抗锥虫化合物

• 批准号: 11672101
• 负责人: KIUCHI Fumiyuki
• 金额: $ 2.18万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672101/
• 关键词: trypanosomiasis; Trypanosoma cruzi; Hela infection assay; natural medicines; Alpinia galanga; Laurus nobilis; Desmos dasymachalus; dasymachaline-N-oxide; Vietnam; 1′-acetoxychavicol acetate; dasymacharine-N-oxide; 天然薬物; ローレル; monoterpene; se

1. Antitrypanosomal screening of natural medicinesAntitrypanosomal activity of natural medicines used in Asian countries was evaluated by an assay system, which models the infection of Trypanosoma cruzi to human cells (HeLa cell). Leaves of Laurus nobilis, seeds of Psoralea corylifolia, and fruits of Piper longum showed strong activity. About 100 natural medicines used in Vietnam were also tested for trypanocidal activity against epimastigotes of T.cruzi. In this assay, rhizomes of Alpinia galanga, whole plant of Dendrobium nobile, roots of Paris polyphilla, etc. showed strong activity.2. Identification of antitrypanosomal principlesThe antitrypanosomal principles of some of the above natural medicines were identified. From the leaves of Laurus nobilis, two sesquiterpene γ-lactones (dehydrocostus lactone, zaluzanin D) and a monoterpene hydroperoxide were isolated. The monoterpene inhibited the infection of trypomastigotes to HeLa cells by 98% as well as the proliferation of amastigotes in HeLa cells by 84% at 1 μg/ml without any toxicity to HeLa cells at 10 μg/ml. From the rhizomes of Alpinia galanga, eight phenylpropanoids, including its major constituent 1'-acetoxychavicol acetate, were isolated as active principles. Comparison of the activity of these phenylpropanoids suggested that the reactivity of the double bond in these compounds is important for the activity. From the roots of Desmos dasymachalus, which are used for dysentery in Sarawak, dasymachaline and its N-oxide were isolated as active components. Trypanocidal activity of the N-oxide was about 10 times stronger than the original alkaloid. This is the first report of trypanocidal activity of an alkaloid N-oxide. This finding will open an access to a new class of natural products having potent antitrypanosomal activity.

1。通过评估系统评估了在亚洲国家使用天然药物的天然药物抗脑体活性的抗胰囊体筛查，该评估系统对Cruzi锥虫感染对人类细胞（HELA细胞）进行了建模。 laurus nobilis的叶子，牛皮利亚牛cor的种子和派珀·龙姆的果实表现出很强的活性。还测试了越南使用的大约100种天然药物，用于针对T.Cruzi的表脂质的锥虫活性。在此测定中，Alpinia galanga的根茎，not虫的整个植物，巴黎Polyphilla的根等表现出很强的活性。2。鉴定抗戊糖体原理鉴定了上述某些天然药物的抗胰植物学原理。分离出从月球叶叶叶叶（Laurus nobilis）的叶子中，分离出两个倍半萜γ-内酯（脱氢可内酯，Zaluzanin d）和一个单萜氢过氧化物。单萜将锥虫对HeLa细胞的感染抑制了98％的感染，以及在HeLa细胞中的amastigotes在1μg/mL时以10μg/mL的毒性抑制了HeLa细胞中的amastigote的感染。从阿尔卑斯山脉的根茎中，包括乙酸乙酸根的主要构成1'-乙酸乙酸盐，包括八个苯基丙糖苷，被分离为活性原理。这些苯基丙烷的活性的比较表明，这些化合物中双键的反应性对于活性很重要。从砂拉越，dasymachaline及其N氧化物的痢疾的Desmos dasymachalus的根部被用作活性成分。 N-氧化物的锥虫活性比原始生物碱强约10倍。这是生物碱N-氧化物的锥虫活性的第一个报告。这一发现将为具有有效的抗丙糖体活动的新型天然产品提供访问。