Betulinic acid derivatives: A new class of specific inhibitors of human immunodeficiency virus type 1 entry
Betulinic acid derivatives: A new class of specific inhibitors of human immunodeficiency virus type 1 entry
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DOI：
10.1021/jm950669u
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发表时间：
1996-03-01
影响因子：
7.3
通讯作者：
Dereu, N
中科院分区：
文献类型：
--
作者：
Soler, F;Poujade, C;Dereu, N
合成了一系列新的桦木酸的欧米伽-氨基烷酸衍生物，并对其抗人类免疫缺陷病毒(HIV)活性进行了评价。这一新系列中的几个成员在CEM 4和MT-4细胞培养中的抗HIV-1活性被发现在纳摩尔范围内。介绍了欧米茄-氨基烷酸侧链的优化。侧链中的酰胺基团的存在对最佳活性很重要。他汀类化合物RPR 103611(14G)对HIV-1蛋白水解酶、逆转录酶、整合酶以及gp120/CD_4结合均无抑制作用。“添加时间”实验表明，这与HIV-1复制的早期步骤存在相互作用。由于合胞体的形成，而不是病毒与细胞的结合似乎受到影响，白桦酸衍生物被认为与结合后的病毒-细胞融合过程相互作用。
A novel series of omega-aminoalkanoic acid derivatives of betulinic acid were synthesized and evaluated for their activity against human immunodeficiency virus (HIV). The anti-HIV-1 activity of several members of this new series was found to be in the nanomolar range in CEM 4 and MT-4 cell cultures. The optimization of the omega-aminoalkanoic acid side chain is described. The presence of an amide function within the side chain was found important for optimal activity. RPR 103611 (14g), a statine derivative, was found to be inactive against HIV-1 protease, reverse transcriptase, and integrase as well as on gp120/CD4 binding. ''Time of addition'' experiments suggested interaction with an early step of HIV-1 replication. As syncytium formation, but not virus-cell binding, seems to be affected, betulinic acid derivatives are assumed to interact with the postbinding virus-cell fusion process.