Synthesis and preliminary evaluation of new ursolic and oleanolic acids derivatives as antileishmanial agents
Synthesis and preliminary evaluation of new ursolic and oleanolic acids derivatives as antileishmanial agents
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DOI：
10.1080/14756360802204870
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发表时间：
2008-01-01
影响因子：
5.6
通讯作者：
Sonnet, Pascal
中科院分区：
文献类型：
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作者：
Gnoatto, Simone C. B.;Dalla Vechia, Luciana;Sonnet, Pascal
从南美冬青属植物中提取熊果酸或熊果酸，合成了一系列新的熊果酸和熊果酸衍生物。测试了这些新化合物对亚马逊利什曼原虫和婴儿利什曼原虫菌株的体外抗寄生虫活性。这些化合物中的一些显示出抗前鞭毛体形式的L。amazonensis或L.婴儿，IC 50范围为5 - 12 μ M。正如所预期的，大多数化合物显示出显著水平的对单核细胞的细胞毒性（IC 50 =2-50 μ M）。从结构-活性关系的角度来看，这些药理学结果主要揭示了齐墩果酸骨架3位乙酰化在抗L. amazonensis菌株，和双-（3-氨丙基）哌嗪部分的羧基功能的熊果酸对L.婴儿菌株
A series of new ursolic and oleanolic acids derivatives was synthesized via ursolic or oleanolic acids, previously extracted from South American Ilex species. These new compounds were tested for in vitro antiparasitic activity on Leishmania amazonensis and Leishmania infantum strains. Some of these compounds showed activity against the promastigote forms of L. amazonensis or L. infantum, with IC50 ranging from 5 to 12 mu M. As expected, most of the compounds showed a significant level of cytotoxicity against monocytes (IC50=2-50 mu M). From a structure-activity relationships point of view, these pharmacological results enlightened mainly the importance of an acetylation at position 3 of the oleanolic acid skeleton in the activity against the L. amazonensis strain, and of a bis-(3-aminopropyl)piperazine moiety on the carboxylic function of ursolic acid against the L. infantum strain.