Toosendanin relatives, trypanocidal principles from Meliae Cortex
Toosendanin relatives, trypanocidal principles from Meliae Cortex
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DOI：
10.1007/s11418-020-01422-9
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发表时间：
2020-06
影响因子：
3.3
通讯作者：
M. N. Mifundu;N. Murakami;Tomikazu Kawano;S. Tamura
中科院分区：
文献类型：
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作者：
M. N. Mifundu;N. Murakami;Tomikazu Kawano;S. Tamura
非洲锥虫病仍然是一个严重的健康问题，但批准用于这种疾病的药物是如此之少，以至于需要新的杀锥虫化合物。为了从药用植物中寻找杀锥虫活性成分，我们从近300种苦楝皮的甲醇提取物中筛选出具有较强杀锥虫活性的甲醇提取物。通过生物活性导向的液-液分配分离和硅胶柱层析技术，最终确定川楝素（1）及其相关物为有效成分。这些活性同系物不仅具有很强的杀锥虫活性，而且细胞毒性很小，显示出良好的选择性指数。综合分离量和杀锥虫活性，1-羟基-2-甲基-2-（2-）-2-甲基-2-（2-）-2-甲基-2-（2-）-甲基-2-（2-此外，还以1为原料，化学合成了1的衍生物，并对其生物活性进行了评价。通过比较它们的杀锥虫活性之间的分离的亲属和1的合成衍生物，环氧化物部分被揭示是必不可少的，其有效的杀锥虫活性。此外，推测3-O-乙酰基和7-羟基是重要的官能团，并阐明了在半缩醛羟基部分引入甲基丙酰基可以增强其杀真菌活性。
Africa Trypanosomiasis remains a serious health problem, but the approved drugs for this disease are so few that novel trypanocidal compounds are demanded. In search for trypanocidal principles from medicinal plants, we found MeOH extracts of Meliae Cortex with potent activity through the screening from about 300 kinds of methanolic extract. By bioassay-guided fractionation from this extract through the liquid–liquid partition and subsequent chromatographic technique using silica gel and ODS, finally we disclosed toosendanin (1) and its relatives as active principles. These active congeners showed not only potent trypanocidal activity but also little cytotoxicity to display the excellent selective index. Taking the isolated amount as well as trypanocidal activity into consideration,1was disclosed to be the responsible active principle in Meliae Cortex. Additionally, the derivatives of1were chemically prepared from 1 and bioactivity of them were also evaluated. Through the comparison with their trypanocidal activity among the isolated relatives and the synthesized derivatives of 1, the epoxide moiety was revealed to be essential for their potent trypanocidal activity. Furthermore, 3-O-acetyl group and 7-hydroxyl group were presumed to be important functional groups and introduction of methylpropionyl group into hemiacetal hydroxy moiety was clarified to enhance their typanocidal activity.