2',3'-二脱氧-2',3'-二氟-D-阿拉伯呋喃糖基-2,6-二取代嘌呤核苷的合成及抗病毒活性评价
Synthesis and antiviral evaluation of 2',3'-dideoxy-2',3'-difluoro-D-arabinofuranosyl 2,6-disubstituted purine nucleosides.
作者信息
Schinazi Raymond F, Sivets Grigorii G, Detorio Mervi A, McBrayer Tami R, Whitaker Tony, Coats Steven J, Amblard Franck
机构信息
Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA; and Veterans Affairs Medical Center, Decatur, GA 30033, USA.
Institute of Bioorganic Chemistry, National Academy of Sciences, Acad. Kuprevicha 5, 220141 Minsk, Belarus.
出版信息
Heterocycl Comm. 2015;21(5):315-327. doi: 10.1515/hc-2015-0174. Epub 2015 Oct 8.
Abstract
The synthesis of new 2,6-disubstituted purine 2',3'-dideoxy-2',3'-difluoro-D-arabino nucleosides is reported. Their ability to block HIV and HCV replication along with their cytotoxicity toward Huh-7 cells, human lymphocyte, CEM and Vero cells was also assessed. Among them, β-2,6-diaminopurine nucleoside and guanosine derivative demonstrate potent anti-HIV-1 activity (EC = 0.56 and 0.65 μM; EC = 4.2 and 3.1 μM) while displaying only moderate cytotoxicity in primary human lymphocytes.
摘要
报道了新型2,6-二取代嘌呤2',3'-二脱氧-2',3'-二氟-D-阿拉伯糖核苷的合成。还评估了它们阻断HIV和HCV复制的能力以及对Huh-7细胞、人淋巴细胞、CEM细胞和Vero细胞的细胞毒性。其中，β-2,6-二氨基嘌呤核苷和鸟苷衍生物表现出强大的抗HIV-1活性（EC₅₀ = 0.56和0.65 μM；EC₉₀ = 4.2和3.1 μM），而在原代人淋巴细胞中仅表现出中等程度的细胞毒性。
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