Characterization of Nine Compounds Isolated from the Acid Hydrolysate of Lonicera fulvotomentosa Hsu et S. C. Cheng and Evaluation of Their In Vitro Activity towards HIV Protease
Characterization of Nine Compounds Isolated from the Acid Hydrolysate of Lonicera fulvotomentosa Hsu et S. C. Cheng and Evaluation of Their In Vitro Activity towards HIV Protease
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从金银花酸水解产物中分离出的九种化合物的表征及其对 HIV 蛋白酶的体外活性评价
DOI：
10.3390/molecules24244526
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发表时间：
2019-12-01
期刊：
影响因子：
4.6
通讯作者：
Yang, Jian
中科院分区：
文献类型：
--
作者：
Wang, Xia;Wei, Ying;Yang, Jian
本研究从黄毛藤花蕾的酸水解液中分离得到9个化合物。C. Cheng等合成并利用1H-NMR、13 C-NMR和电子电离质谱（EI-MS）表征了它们的化学结构。这些化合物分别鉴定为β-谷甾醇（1）、5，5 ′-二丁氧基-2，2 ′-联呋喃（2）、二十九烷-10-醇（3）、（3β）-3，23-二羟基-12-烯-28-酸乙酯（4）、油酸（5）、咖啡酸乙酯（6）、咖啡酸（7）、异香草醛（8）和常春藤皂苷元（9），其中4个为新的三萜化合物。还评价了化合物对人类免疫缺陷病毒（HIV）蛋白酶的抑制活性，只有咖啡酸乙酯、咖啡酸和异香草醛（6、7和8）表现出抑制作用，IC 50值分别为1.0 μM、1.5 μM和3.5 μM。分子对接与能量最小化和随后的分子动力学（MD）模拟表明，咖啡酸乙酯和咖啡酸结合到HIV蛋白酶的活性位点，而异香草醛漂移出的活性位点，解离成散装水在MD模拟，和HIV蛋白酶的结合残基的HIV蛋白酶抑制剂以前已被确定。这些结果表明，咖啡酸衍生物可能具有对HIV蛋白酶的抑制活性，而不是以前报道的对HIV整合酶的抑制活性，因此咖啡酸乙酯和咖啡酸可用作开发潜在的HIV蛋白酶抑制剂的先导化合物，甚至可能是抗HIV的双功能抑制剂。
In this study, we isolated nine compounds from the acid hydrolysate of the flower buds of Lonicera fulvotomentosa Hsu et S. C. Cheng and characterized their chemical structures using 1H-NMR, 13C-NMR, and electron ionization mass spectroscopy (EI-MS). These compounds were identified as β-sitosterol (1), 5,5′-dibutoxy-2,2′-bifuran (2), nonacosane-10-ol (3), ethyl (3β)-3,23-dihydroxyolean-12-en-28-oate (4), oleanolic acid (5), ethyl caffeate (6), caffeic acid (7), isovanillin (8), and hederagenin (9), with 4 as a new triterpene compound. Inhibitory activity against human immunodeficiency virus (HIV) protease was also evaluated for the compounds, and only ethyl caffeate, caffeic acid, and isovanillin (6, 7, and 8) exhibited inhibitory effects, with IC50 values of 1.0 μM, 1.5 μM, and 3.5 μM, respectively. Molecular docking with energy minimization and subsequent molecular dynamic (MD) simulation showed that ethyl caffeate and caffeic acid bound to the active site of HIV protease, while isovanillin drifted out from the active site and dissociated into bulk water during MD simulations, and most of the binding residues of HIV protease have been previously identified for HIV protease inhibitors. These results suggest that caffeic acid derivatives may possess inhibitory activities towards HIV protease other than previously reported inhibitory activities against HIV integrase, and thus ethyl caffeate and caffeic acid could be used as lead compounds in developing potential HIV protease inhibitors, and possibly even dual-function inhibitors against HIV.