新型茚满核苷类似物的合成及其对丙型肝炎病毒（HCV）复制子的生物学评价。

Synthesis of New Indanyl Nucleoside Analogues and their Biological Evaluation on Hepatitis C Virus (HCV) Replicon.

机构信息

Cátedra de Química Medicinal, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires C1113AAD, Argentina.

Instituto de Investigaciones en Microbiología y Parasitología Médica, CONICET-Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires C1121ABF, Argentina.

出版信息

Molecules. 2019 Mar 11;24(5):990. doi: 10.3390/molecules24050990.

DOI:10.3390/molecules24050990

PMID:30862130

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6429379/

Abstract

Here, we report a convenient synthetic procedure for the preparation of four novel indanyl carbanucleoside derivatives in the racemic form. The action of these compounds against hepatitis C virus was evaluated in vitro using the replicon cell line, Huh7.5 SG. Contrary to our expectations, all these compounds did not inhibit, but rather promoted HCV genotype 1b (HCVg1b) replication. Similar effects have been reported for morphine in the replicon cell lines, Huh7 and Huh8. Several biological experiments and computational studies were performed to elucidate the effect of these compounds on HCVg1b replication. Based on all the experiments performed, we propose that the increase in HCVg1b replication could be mediated, at least in part, by a similar mechanism to that of morphine on the enhancement of this replication. The presence of opioid receptors in Huh7.5 SG cells was indirectly determined for the first time in this work.

摘要

在这里，我们报告了一种方便的合成方法，用于制备四种新型茚满碳核苷衍生物的外消旋形式。这些化合物对丙型肝炎病毒的作用在体外使用复制子细胞系 Huh7.5 SG 进行了评估。与我们的预期相反，所有这些化合物都没有抑制，而是促进了丙型肝炎病毒 1b 型 (HCVg1b) 的复制。类似的作用也在复制子细胞系 Huh7 和 Huh8 中报道了吗啡的作用。进行了几项生物学实验和计算研究，以阐明这些化合物对 HCVg1b 复制的影响。基于所有进行的实验，我们提出 HCVg1b 复制的增加至少部分可以通过与吗啡相似的机制介导，以增强这种复制。这项工作首次间接确定了 Huh7.5 SG 细胞中阿片受体的存在。