Design, synthesis, and bio-evaluation of novel triterpenoid derivatives as anti-HIV-1 compounds
Design, synthesis, and bio-evaluation of novel triterpenoid derivatives as anti-HIV-1 compounds
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作为抗 HIV-1 化合物的新型三萜衍生物的设计、合成和生物评价
DOI：
10.1016/j.bmcl.2022.128768
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Narumi Tetsuo
中科院分区：
文献类型：
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作者：
Takeuchi Reon;Ogihara Kasumi;Fujimoto Junko;Sato Kohei;Mase Nobuyuki;Yoshimura Kazuhisa;Harada Shigeyoshi;Narumi Tetsuo
两种桦木酸衍生物RPR 103611（2）和IC 9564（3）先前已被报道为有效的HIV-1进入抑制剂。在本研究中，对2和3的三萜类化合物部分进行了SAR研究，并鉴定了油酸衍生物（4）为新型HIV-1进入抑制剂。此外，4与几种类型的HIV-1中和抗体的组合提供了显著的协同效应。4的C-环中的C双键的合成效用也被证明可用于开发作为有效抗HIV化合物的12-酮型油酸衍生物（5）。这种简单的转化导致化合物的抗HIV活性显著增加和细胞毒性降低。
Two betulinic acid derivatives, RPR103611 (2) and IC9564 (3) were previously reported to be potent HIV-1 entry inhibitors. In this current study, a SAR study of the triterpenoid moiety of2and3has been performed and an oleanolic acid derivative (4)was identified as a novel HIV-1 entry inhibitor. In addition, the combination of4with several-type of HIV-1 neutralizing antibodies provided significant synergistic effects. The synthetic utility of the Cdouble bondC double bond in the C-ring of4was also demonstrated to develop the 12-keto-type oleanolic acid derivative (5) as a potent anti-HIV compound. This simple transformation led to a significantly increased anti-HIV activity and a reduced cytotoxicity of the compound.