期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 69, 期 -, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2022.128768
关键词
Triterpenoid; HIV-1 entry inhibitor; Anti-HIV-1 activity; SAR study; Neutralizing antibodies
资金
- AMED, Japan [JP16fk0410106]
In this study, a novel HIV-1 entry inhibitor oleanolic acid derivative was discovered and it was found that modifying the structure of the compound significantly increased its anti-HIV activity and reduced cytotoxicity.
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 of 2 and 3 has been performed and an oleanolic acid derivative (4) was identified as a novel HIV-1 entry inhibitor. In addition, the combination of 4 with several-type of HIV-1 neutralizing antibodies provided significant synergistic effects. The synthetic utility of the C=C double bond in the C-ring of 4 was also demonstrated to develop the 12-keto-type oleanolic acid de-rivative (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.
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