Li Weijia, Yang Fan, Meng Lingkuan, Sun Jiaqi, Su Yangqing, Shao Liang, Zhou Demin, Yu Fei
Medical School of Kunming University of Science and Technology.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University.
Chem Pharm Bull (Tokyo). 2019 Nov 1;67(11):1201-1207. doi: 10.1248/cpb.c19-00485. Epub 2019 Aug 22.
Oleanolic acid (OA) was discovered as a mild influenza hemagglutinin (HA) inhibitor in our earlier studies. In the present work, 20 compounds were prepared by structural modifications of OA, and their antiviral activities against influenza A/WSN/33 (H1N1) virus in Madin-Darby canine kidney (MDCK) cells were evaluated. Based on the biological result, structure-activity relationship (SAR) was discussed. Compound 10 with six-carbon chain and a terminal hydroxyl group showed the strongest anti-influenza activity with an IC of 2.98 µM, which is an order of magnitude more potent than OA. Hemagglutination inhibition and Surface plasmon resonance (SPR) assay indicated that compound 10 might interfere with influenza invasion by interacting with HA protein.
在我们早期的研究中发现齐墩果酸（OA）是一种温和的流感血凝素（HA）抑制剂。在本研究中，通过对齐墩果酸进行结构修饰制备了20种化合物，并评估了它们在麦迪逊-达比犬肾（MDCK）细胞中对甲型流感病毒A/WSN/33（H1N1）的抗病毒活性。基于生物学结果，讨论了构效关系（SAR）。具有六碳链和末端羟基的化合物10表现出最强的抗流感活性，IC50为2.98μM，比齐墩果酸的活性高一个数量级。血凝抑制和表面等离子体共振（SPR）分析表明，化合物10可能通过与HA蛋白相互作用来干扰流感病毒的入侵。
