Xia Cheng-lai, Mao Qin-chao, Li Run-ming, Chen Zhi-peng, Jiang Shi-bo, Jiang Zhi-hong, Liu Shu-wen
School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2010 Apr;30(4):720-3.
To investigate the inhibitory activities of caffeoyl glucopyranoses purified from Balanophora japonica Makino on HIV entry and their mechanism.
HIV-1 Env pseudovirus was used to evaluate the anti-HIV-1 activity of those compounds. ELISA and molecular docking were used to study the mechanism of the actions of the active compounds.
We used the HIV-1 Env pseudovirus to test the anti-HIV-1 activity of the six phenolic compounds (final concentration 25 microg/ml), and found that only 1,2,6-Tri-O-caffeoyl-beta-D-glucopyranose (TCGP) and 1,3-Di-O-caffeoyl-4-O-galloyl-beta-D- glucopyranose (DCGGP) could effectively inhibit the entry of HIV-1 Env pseudovirus into the target cells in a dose-dependent manner, with IC(50) values of 5.5-/+0.2 and 5.3-/+0.1 microg/ml, respectively. These two compounds could also blocked the gp41 six-helix bundle formation. Molecular docking analysis suggested that they might bind to the hydrophobic cavity of the gp41 N-trimeric coiled-coil.
TCGP and DCGGP are potent HIV-1 entry inhibitors targeting gp41 and can serve as lead compounds for developing novel anti-HIV-1 microbicides for prevention of sexual HIV-1 transmission.
研究从日本蛇菰中纯化得到的咖啡酰葡萄糖苷对HIV进入细胞的抑制活性及其作用机制。
利用HIV-1 Env假病毒评估这些化合物的抗HIV-1活性。采用酶联免疫吸附测定法（ELISA）和分子对接技术研究活性化合物的作用机制。
我们用HIV-1 Env假病毒检测了6种酚类化合物（终浓度25μg/ml）的抗HIV-1活性，发现只有1,2,6-三-O-咖啡酰-β-D-葡萄糖苷（TCGP）和1,3-二-O-咖啡酰-4-O-没食子酰-β-D-葡萄糖苷（DCGGP）能以剂量依赖方式有效抑制HIV-1 Env假病毒进入靶细胞，IC50值分别为5.5±0.2和5.3±0.1μg/ml。这两种化合物还能阻断gp41六螺旋束的形成。分子对接分析表明，它们可能与gp41 N-三聚体卷曲螺旋的疏水腔结合。
TCGP和DCGGP是靶向gp41的强效HIV-1进入抑制剂，可作为开发新型抗HIV-1杀微生物剂以预防性传播HIV-1的先导化合物。
