羟基脲增强外周血单核细胞中2'-β-氟-2',3'-二脱氧腺苷对1型人类免疫缺陷病毒的抗病毒效力。
Enhancement by hydroxyurea of the anti-human immunodeficiency virus type 1 potency of 2'-beta-fluoro-2',3'-dideoxyadenosine in peripheral blood mononuclear cells.
作者信息
Gao W Y, Mitsuya H, Driscoll J S, Johns D G
机构信息
Experimental Retrovirology Section, NCI, National Institutes of Health, Bethesda, MD 20982, USA.
出版信息
Biochem Pharmacol. 1995 Jul 17;50(2):274-6. doi: 10.1016/0006-2952(95)00106-a.
Ribonucleotide reductase inhibitors such as hydroxyurea (HU) and related compounds, at low, non-toxic doses, enhance the anti-human immunodeficiency virus type 1 (HIV-1) potency of both purine and pyrimidine 2',3'-dideoxynucleosides (ddNs) in human lymphocytes and macrophages. The most marked enhancement of inhibition of HIV-1 replication reported to date has been seen with the purine ddN 2',3'-dideoxyinosine (ddIno): a low level of HU (0.1 mM) permitted a 4.5-fold reduction in optimal ddIno dosage with no decrease in therapeutic effect or increase in toxicity. We report here even more marked enhancement by HU of the potency of the purine ddN 2'-beta-fluoro-2',3'-dideoxyadenosine (2'-beta-F-ddAdo), where the addition of 0.1 mM HU permitted a 7.1-fold reduction in the optimal dose of 2'-beta-F-ddAdo in the phytohemagglutinin-activated peripheral blood mononuclear cell HIV-1 test system.
核糖核苷酸还原酶抑制剂，如羟基脲（HU）及相关化合物，在低无毒剂量下，可增强嘌呤和嘧啶2',3'-双脱氧核苷（ddNs）对人淋巴细胞和巨噬细胞中1型人类免疫缺陷病毒（HIV-1）的抑制效力。迄今为止，在嘌呤双脱氧核苷2',3'-双脱氧肌苷（ddIno）中观察到对HIV-1复制抑制的最显著增强：低水平的HU（0.1 mM）使最佳ddIno剂量降低了4.5倍，而治疗效果未降低，毒性也未增加。我们在此报告，HU对嘌呤双脱氧核苷2'-β-氟-2',3'-双脱氧腺苷（2'-β-F-ddAdo）效力的增强更为显著，在植物血凝素激活的外周血单核细胞HIV-1测试系统中，添加0.1 mM HU可使2'-β-F-ddAdo的最佳剂量降低7.1倍。
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