DNA TOPOMERASE 1 ACTIVITY IN RETROVIRUSES

此前有报道称，有几种逆转录病毒和慢病毒 颗粒含有一种新的拓扑异构酶I(Topo I)活性，并且 这种酶的特定抑制剂喜树碱可以阻止艾滋病毒感染 在不具有细胞毒性的浓度下对H9细胞进行杀伤。为了努力 鉴定喜树碱的衍生物，这些衍生物可能会显示出改进的 具有较低细胞毒性的抗病毒活性，由20个衍生物组成的小组 对CPT进行筛选，以确定其抑制组织中HIV感染的能力 文化。结果表明，以前已知的衍生品 拓扑异构酶I活性的无效抑制剂没有显示出抑制作用 爱滋病毒。在体外能够抑制Topo I活性的衍生物能够 抑制HIV感染H9，但均表现出明显的细胞毒作用。 没有一种被测试的衍生品抗病毒效果显著。 药剂比母体化合物喜树碱。

It was previously reported that several retrovirus and lentivirus particles contained a novel topoisomerase I (topo I) activity and that the specific inhibitor of this enzyme, camptothecin, could block HIV infection of H9 cells at concentrations which were not cytotoxic. In an effort to identify derivatives of camptothecin which might exhibit an improved antiviral activity with lower cytotoxicity, a panel of 20 derivatives of CPT were screened for their ability to inhibit HIV infection in tissue culture. Results indicated that derivatives previously known to be ineffective inhibitors of topoisomerase I activity showed no inhibition of HIV. Derivatives capable of inhibiting topo I activity in vitro were able to inhibit HIV infection of H9, but all showed significant cytotoxicity. None of the derivatives tested were significantly more effective antiviral agents than the parent compound camptothecin.