Anti-AIDS agents 38.: Anti-HIV activity of 3-O-acyl ursolic acid derivatives
Anti-AIDS agents 38.: Anti-HIV activity of 3-O-acyl ursolic acid derivatives
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DOI：
10.1021/np990633v
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发表时间：
2000-12-01
影响因子：
5.1
通讯作者：
Lee, KH
中科院分区：
文献类型：
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作者：
Kashiwada, Y;Nagao, T;Lee, KH
基于我们先前的发现，3-O-酰基-白桦酸和-齐墩果酸，特别是3-O-(3‘，3’-二甲基)-琥珀酸衍生物(2和4)具有很强的抗艾滋病毒活性[EC50；0.00035和0.00086 M；治疗指数(TI)；20000和22326]，我们合成了几种3-O-酰基-熊果酸，并对其抗艾滋病毒活性进行了评价。熊果酸(6)与齐墩果酸(EC_(50)为3.7um)具有等效性(EC_(50)为4.4um)，但毒性较小(IC_(50)为14.3CIM，TI为3.3)。3-O-二甘草酰-熊果酸(10)具有较强的抗HIV活性，其EC_(50)为0.31um，TI为155.5。相反，3-O-(3‘，3’-二甲基琥珀酰基)熊果酸(8)，类似于极强的抗HIV白桦酸和齐墩果酸衍生物2和4，只有微弱的抗HIV活性(EC_(50)2.1um，TI 23.6)。
Based on our previous finding that 3-O-acyl-betulinic and -oleanolic acids, especially the 3-O-(3',3'-dimethyl)-succinyl derivatives (2 and 4), demonstrated potent anti-HIV activity [EC50 < 0.00035 and 0.00086 M; therapeutic index (TI) > 20 000 and 22 326, respectively], several 3-O-acyl-ursolic acids were prepared and evaluated for anti-HIV activity. Ursolic acid (6) was equipotent (EC50 4.4 muM) with oleanolic acid (EC50 3.7 muM), although it was slightly toxic (IC50 14.3 CIM, TI 3.3). 3-O-Diglycoryl-ursolic acid (10) demonstrated relatively potent anti-HIV activity with an EC50 of 0.31 muM and a TI of 155.5. In contrast, 3-O-(3',3'-dimethylsuccinyl)-ursolic acid (8), which is analogous to the extremely potent anti-HIV betulinic acid and oleanolic acid derivatives 2 and 4, displayed only weak anti-HIV activity (EC50 2.1 muM, TI 23.6).