基于前药策略的抗hiv -1 Vif抑制剂的设计、合成及生物学评价。

IF 2.2 4区 医学 Q3 CHEMISTRY, MEDICINAL
Weilin Wang, Rui Deng, Rong-Hua Luo, Hongjia Zhang, Dan Luo, Shirui Wang, Su Yu, Xinyu Ma, Chunlan Pu, Yuanyuan Liu, Qing Huang, Liu-Meng Yang, Yong-Tang Zheng, Rui Li
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引用次数: 0

摘要

在这项工作中,我们描述了一系列同时靶向HIV-1病毒感染因子(Vif)和逆转录酶(RT)的新型双靶点前药的设计、合成和生物学评价。其中,最有效的两种化合物A1和A7在C8166细胞中具有纳米摩尔浓度(EC50 = 8.1 nM, EC50 = 9.4 nM)对HIV-1IIIB的抑制作用,分别比母药6 m高95和81倍,比司他夫定(d4T)高2.7和2.3倍。化合物A1在培养基中的稳定性表明,它能有效释放母体药物6 m和他夫定,半衰期为6 h,提示它是一种潜在的靶向HIV Vif和逆转录酶的双靶点前药。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Design, synthesis and biological evaluation of anti-HIV-1 Vif inhibitors based on prodrug strategy.

In this work, we describe the design, synthesis, and biological evaluation of a series of novel dual-target prodrugs that simultaneously target HIV-1 viral infection factors (Vif) and reverse transcriptase (RT). Among them, the two most effective compounds, A1 and A7, were found to inhibit HIV-1IIIB at nanomolar concentrations (EC50 = 8.1 nM, EC50 = 9.4 nM) in C8166 cells, which were 95 and 81 times higher than the parent drug 6 m, respectively, and 2.7 and 2.3 times higher than that of stavudine (d4T). The stability of compound A1 in the medium suggests that it can effectively release the parent drugs 6 m and stavudine with a half-life of 6 h, suggesting that it is a potential dual-target prodrug targeting HIV Vif and reverse transcriptase.

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来源期刊
CiteScore
5.70
自引率
3.70%
发文量
463
审稿时长
27 days
期刊介绍: Bioorganic & Medicinal Chemistry Letters presents preliminary experimental or theoretical research results of outstanding significance and timeliness on all aspects of science at the interface of chemistry and biology and on major advances in drug design and development. The journal publishes articles in the form of communications reporting experimental or theoretical results of special interest, and strives to provide maximum dissemination to a large, international audience.
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