Broom A D, Agrawal V K, Tutonda M G, Fain H D, Buckheit R W
Department of Medicinal Chemistry, College of Pharmacy, University of Utah, Salt Lake City 84112, USA.
J Med Chem. 1995 Aug 18;38(17):3253-7. doi: 10.1021/jm00017a009.
Polyribonucleotides (PTMG and PMTI) containing 1-methyl-6-thioguanosine or 1-methyl-6-thioinosine, respectively, as the sole nucleoside component are shown to be potent inhibitors of various strains of HIV-1 and HIV-2 in a number of human lymphocyte and macrophage cell lines in tissue culture as well as in fresh human peripheral blood lymphocytes and macrophages. PMTI and PMTG exhibit potencies in the range of 10(-7)-10(-8) M in these systems. The polynucleotides are active against virus strains resistant to AZT and pyridinone derivatives. Both PMTI and PMTG are synergistic with AZT and with ddI, and both inhibit HIV reverse transcriptase at nanomolar concentrations. The polymers show little or no toxicity in human cell lines at the highest doses tested (100 micrograms/mL, or about 0.2-1 microM). This class of compounds represents a new lead in AIDS therapeutic drug discovery.
分别含有1 - 甲基 - 6 - 硫代鸟苷或1 - 甲基 - 6 - 硫代肌苷作为唯一核苷成分的多聚核糖核苷酸（PTMG和PMTI），在组织培养中的多种人类淋巴细胞和巨噬细胞系以及新鲜的人类外周血淋巴细胞和巨噬细胞中，被证明是多种HIV - 1和HIV - 2毒株的有效抑制剂。在这些系统中，PMTI和PTMG的效力范围为10(-7)-10(-8) M。这些多聚核苷酸对耐齐多夫定（AZT）和吡啶酮衍生物的病毒株有活性。PMTI和PTMG与AZT以及双脱氧肌苷（ddI）都具有协同作用，并且两者在纳摩尔浓度下都能抑制HIV逆转录酶。在测试的最高剂量（100微克/毫升，约为0.2 - 1微摩尔）下，这些聚合物在人类细胞系中几乎没有或没有毒性。这类化合物代表了艾滋病治疗药物研发中的一个新线索。
