Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Salamanca, CIETUS-IBSAL, 37007 Salamanca, Spain.
Molecules. 2012 Aug 2;17(8):9245-57. doi: 10.3390/molecules17089245.
We have synthesized fourteen 3-phenylcoumarin derivatives and evaluated their anti-HIV activity. Antiviral activity was assessed on MT-2 cells infected with viral clones carrying the luciferase gene as reporter. Inhibition of HIV transcription and Tat function were tested on cells stably transfected with the HIV-LTR and Tat protein. Six compounds displayed NF-κB inhibition, four resulted Tat antagonists and three of them showed both activities. Three compounds inhibited HIV replication with IC₅₀ values < 25 µM. The antiviral effect of the 4-hydroxycoumarin derivative 19 correlates with its specific inhibition of Tat functions, while compound 8, 3-(2-chlorophenyl)coumarin, seems to act through a mechanism unrelated to the molecular targets considered in this research.
我们合成了 14 种 3-苯基香豆素衍生物，并评估了它们的抗 HIV 活性。在感染带有荧光素酶基因作为报告基因的病毒克隆的 MT-2 细胞上评估抗病毒活性。在稳定转染 HIV-LTR 和 Tat 蛋白的细胞上测试 HIV 转录和 Tat 功能的抑制作用。六种化合物显示出 NF-κB 抑制作用，四种化合物是 Tat 拮抗剂，其中三种具有这两种活性。三种化合物的 HIV 复制抑制作用的 IC₅₀ 值<25µM。4-羟基香豆素衍生物 19 的抗病毒作用与其对 Tat 功能的特异性抑制相关，而化合物 8、3-(2-氯苯基)香豆素似乎通过与本研究中考虑的分子靶标无关的机制起作用。
