THERAPEUTIC AGENTS WITH DRAMATIC ANTIRETROVIRAL ACTIVITY AND LITTLE TOXICITY AT EFFECTIVE DOSES - AROMATIC POLYCYCLIC DIONES HYPERICIN AND PSEUDOHYPERICIN
THERAPEUTIC AGENTS WITH DRAMATIC ANTIRETROVIRAL ACTIVITY AND LITTLE TOXICITY AT EFFECTIVE DOSES - AROMATIC POLYCYCLIC DIONES HYPERICIN AND PSEUDOHYPERICIN
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DOI：
10.1073/pnas.85.14.5230
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发表时间：
1988-07-01
影响因子：
11.1
通讯作者：
LAVIE, D
中科院分区：
文献类型：
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作者：
MERUELO, D;LAVIE, G;LAVIE, D
两种芳香族多环二酮金丝桃素和假金丝桃素具有强效的抗逆转录病毒活性;这些物质存在于金丝桃科植物中。这两种化合物在体内和体外预防各种逆转录病毒感染后病毒诱导的表现方面非常有效。假金丝桃素和金丝桃素可能通过直接灭活病毒或通过阻止病毒脱落、出芽或在细胞膜上组装来干扰病毒感染和/或传播。这些化合物对病毒蛋白质的转录、翻译或转运到细胞膜没有明显的活性，也对聚合酶没有直接影响。这一特性将它们的作用模式与核苷类似物的主要抗逆转录病毒组的作用模式区分开来。金丝桃素和假金丝桃素在足以在使用放射性白血病和Friend病毒的鼠组织培养模型系统中产生显著的抗病毒作用的浓度下具有低的体外细胞毒性活性。以足以预防逆转录病毒诱导的疾病的低剂量向小鼠施用这些化合物似乎没有不期望的副作用。这种在治疗剂量下缺乏毒性的情况延伸到人类，因为这些化合物已经在患者中作为抗抑郁药进行了测试，具有明显的有益效果。我们迄今的观察表明，假金丝桃素和金丝桃素可以成为治疗逆转录病毒引起的疾病，如获得性免疫缺陷综合征（艾滋病）的工具。
Two aromatic polycyclic diones hypericin and pseudohypericin have potent antiretroviral activity; these substances occur in plants of the Hypericum family. Both compounds are highly effective in preventing viral-induced manifestations that follow infections with a variety of retroviruses in vivo and in vitro. Pseudohypericin and hypericin probably interfere with viral infection and/or spread by direct inactivation of the virus or by preventing virus shedding, budding, or assembly at the cell membrane. These compounds have no apparent activity againts the transcription, translation, or transport of viral proteins to the cell membrane and also no direct effect on the polymerase. This property distinguishes their mode of action from that of the major antiretrovirus group of nucleoside analogues. Hypericin and pseudohypericin have low in vitro cytotoxic activity at concentrations sufficient to produce dramatic antiviral effects in murine tissue culture model systems that use radiation leukemia and Friend viruses. Administration of these compounds to mice at the low doses sufficient to prevent retroviral-induced disease appears devoid of undesirable side effects. This lack of toxicity at therapeutic doses extends to humans, as these compounds have been tested in patients as antidepressants with apparent salutary effects. Our observations to date suggest that pseudohypericin and hypericin could become therapeutic tools against retroviral-induced diseases such as acquired immunodeficiency syndrome (AIDS).