Synthesis and anti-HIV activity of bi-functional betulinic acid derivatives
Synthesis and anti-HIV activity of bi-functional betulinic acid derivatives
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DOI：
10.1016/j.bmc.2005.11.016
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发表时间：
2006-04-01
影响因子：
3.5
通讯作者：
Chen, CH
中科院分区：
文献类型：
--
作者：
Huang, L;Ho, P;Chen, CH
侧链位于C-3的白桦酸(BA)衍生物可以抑制HIV-1的成熟。另一方面，C-28上带有侧链的BA衍生物可以阻止HIV-1的入侵。为了在单分子中结合抗成熟和抗侵入活性，合成了C-3和C-28侧链的新型双功能BA衍生物。最有效的化合物([N-[3 beta-O-(3‘，3’-dimethylsuccinyt)-lup-20(29)-en-28-oyl]-7-aminoheptyl]-carbamoyllmethane)])在EC50值为0.0026微米时抑制艾滋病毒-1，其效力至少是抗成熟铅化合物DSB或抗侵入铅化合物IC9564的20倍。这种双功能BA衍生物具有抗HIV进入和成熟的活性。这些结果表明，具有双重作用机制的双功能BA衍生物有可能成为艾滋病治疗的临床有用药物。(C)2005爱思唯尔有限公司。保留所有权利。
Betulinic acid (BA) derivatives with a side chain at C-3 can inhibit HIV-1 maturation. On the other hand, BA derivatives with a side chain at C-28 can block HIV-1 entry. In order to combine the anti-maturation and anti-entry activities in a single molecule, new bi-functional BA derivatives containing side chains at C-3 and C-28 have been synthesized. The most potent compound ([[N-[3 beta-O-(3',3'-dimethylsuccinyt)-lup-20(29)-en-28-oyl]-7-aminoheptyl]-carbamoyllmethane) inhibited HIV-1 at an EC50 of 0.0026 mu M and was at least 20 times more potent than either the anti-maturation lead compound DSB or the anti-entry lead compound IC9564. This bi-functional BA derivative was active against both HIV entry and maturation. These results suggest that bi-functional BA derivatives with dual mechanisms of action have the potential to become clinically useful for AIDS therapy. (c) 2005 Elsevier Ltd. All rights reserved.