HIV-1整合酶抑制剂的结构方面:SAR研究和合成策略。

IF 3.9 2区 化学 Q2 CHEMISTRY, APPLIED
Pallavi Barik, Shankar Gupta, Gurpreet Singh, Sanjay Kumar Bharti, Vivek Asati
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引用次数: 0

摘要

获得性免疫缺陷综合症(艾滋病)对生命构成重大威胁。抗逆转录病毒疗法用于减少人类免疫缺陷病毒(艾滋病毒)的复制,延长预期寿命并改善患者的生活质量。这些HIV-1整合酶抑制剂与Mg2+离子形成强大的共价相互作用,有助于它们的紧密结合,从而抑制病毒DNA整合到CD4细胞DNA中。与第一代药物相比,最近批准的第二代药物具有更高的遗传屏障。因此,有必要开发新的和安全的化合物作为HIV-1整合酶的抑制剂。本文概述了抗hiv -1整合酶抑制剂的现状,强调了小分子的构效关系(SAR)。所讨论的分子包括由三唑部分组成的单环、嘧啶类似物以及含氮部分的双环。研究人员正在从海洋环境、植物提取物和微生物产品等天然来源中探索抗hiv -1整合酶抑制剂,强调多种生物活性化合物在对抗病毒中的重要性,这些也包括在手稿中。目前的手稿将有助于科学界从事小分子作为抗hiv整合酶抑制剂的操作,以设计新的先导。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Structural aspects of HIV-1 integrase inhibitors: SAR studies and synthetic strategies.

Acquired immunodeficiency syndrome (AIDS) poses a significant threat to life. Antiretroviral therapy is employed to diminish the replication of the human immunodeficiency virus (HIV), extending life expectancy and improving the quality of patients' lives. These HIV-1 integrase inhibitors form robust covalent interactions with Mg2+ ions, contributing to their tight binding, thereby inhibiting the integration of viral DNA into the CD4 cell DNA. The second-generation INSTIs, the most recently approved, exhibit a higher genetic barrier compared to first-generation drugs. Hence, there is a need to develop novel and safe compounds as inhibitors of HIV-1 integrase. This article presents an overview of the current landscape of anti-HIV-1 integrase inhibitors, emphasizing the structure-activity relationship (SAR) of small molecules. The molecules discussed include monocyclic rings consisting of triazoles moiety, and pyrimidine analog along with bicyclic rings with nitrogen-containing moieties. Researchers are exploring anti-HIV-1 integrase inhibitors from natural sources like marine environments, plant extracts, and microbial products, emphasizing the importance of diverse bioactive compounds in combating the virus, which have also been included in the manuscript. The current manuscript will be helpful to the scientific community engaged in the manipulation of small molecules as anti-HIV integrase inhibitors for designing newer leads.

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来源期刊
Molecular Diversity
Molecular Diversity 化学-化学综合
CiteScore
7.30
自引率
7.90%
发文量
219
审稿时长
2.7 months
期刊介绍: Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;
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