Anti-AIDS agents. 30. Anti-HIV activity of oleanolic acid, pomolic acid, and structurally related triterpenoids
Anti-AIDS agents. 30. Anti-HIV activity of oleanolic acid, pomolic acid, and structurally related triterpenoids
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DOI：
10.1021/np9800710
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发表时间：
1998-09-01
影响因子：
5.1
通讯作者：
Lee, KH
中科院分区：
文献类型：
--
作者：
Kashiwada, Y;Wang, HK;Lee, KH
油酸（1）被鉴定为来自几种植物的抗HIV成分，包括Rosa woodsii（叶）、Prosopis glandulosa（叶和枝）、Phoradendron juniperinum（整株）、Syzygium claviflorum（叶）、Hyptis capitata（整株）和Ternstromia gymnanthera（地上部分）。在急性感染的H9细胞中，它抑制HIV-1复制的EC 50值为1.7 μ g/mL，抑制H9细胞生长的IC 50值为21.8 μ g/mL [治疗指数（T.（一）12.8]。波莫酸是从R. woodsii和H. capitata也被鉴定为抗HIV剂（EC_（50）1.4 μ g/mL，T. I. 16.6）。尽管熊果酸确实表现出抗HIV活性（EC 50 2.0 μ g/mL），但它有轻微毒性（IC 50 6.5 μ g/mL，T. I. 3.3）。同时，还从红毛菊的氯仿可溶部分中分离到一个新的三萜（11）。woodsii，但没有显示出抗HIV活性。通过光谱检查确定11的结构为1 β-羟基-2-氧代冰片酸。基于这些结果，我们研究了从几种植物中分离的齐墩果酸或pomolic酸相关的三萜的抗HIV活性。此外，我们以前证明，白桦酸的衍生物，分离自S。claviflorum作为一种抗HIV成分，表现出极强的抗HIV活性。因此，我们制备了油酸衍生物，并评价了它们的抗HIV活性。在油酸衍生物中，18种表现出最有效的抗HIV活性，其EC 50值为0.0005 μ g/mL，T. I.价值22400
Oleanolic acid (1) was identified as an anti-HIV principle from several plants, including Rosa woodsii (leaves), Prosopis glandulosa (leaves and twigs), Phoradendron juniperinum (whole plant), Syzygium claviflorum (leaves), Hyptis capitata (whole plant), and Ternstromia gymnanthera (aerial part). It inhibited HIV-1 replication in acutely infected H9 cells with an EC50 value of 1.7 mu g/mL, and inhibited H9 cell growth with an IC50 value of 21.8 mu g/mL [therapeutic index (T. I.) 12.8]. Pomolic acid, isolated from R. woodsii and H. capitata, was also identified as an anti-HIV agent (EC50 1.4 mu g/mL, T. I. 16.6). Although ursolic acid did show anti-HIV activity (EC50 2.0 mu g/mL), it was slightly toxic (IC50 6.5 mu g/mL, T. I. 3.3). A new triterpene (11) was also isolated from the CHCl3-soluble fraction of R. woodsii, though it showed no anti-HIV activity. The structure of 11 was determined to be 1 beta-hydroxy-2-oxopomolic acid by spectral examination. Based on these results, we examined the anti-HIV activity of oleanolic acid- or pomolic acid-related triterpenes isolated from several plants. In addition, we previously demonstrated that derivatives of betulinic acid, isolated from the leaves of S. claviflorum as an anti-HIV principle, exhibited extremely potent anti-HIV activity. Accordingly, we prepared derivatives of oleanolic acid and evaluated their anti-HIV activity. Among the oleanolic acid derivatives, 18 demonstrated most potent anti-HIV activity, with an EC50 value of 0.0005 mu g/mL and a T. I. value of 22 400.