艾滋病毒衍生逆转录酶抑制的体外研究

Hussan Ibne Shoukani, Khudija tul Kubra, Bashir Ahmad
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引用次数: 0

摘要

艾滋病毒利用逆转录酶(RT)将 HIVRNA 转化为 DNA。非核苷类逆转录酶抑制剂(NNRTIs)是一种直接与 HIV-RT 的异构位点非竞争性结合的药物,可抑制其聚合酶活性。本研究旨在合成肼衍生物,并使用基于 RT-qPCR 的检测方法评估其对 HIV 逆转录酶的抑制作用。本研究的目的是利用化学化合物作为 RT-qPCR 中的非核苷类逆转录酶抑制剂,确定其对 HIV 逆转录酶的抑制作用。本研究涉及合成五种不同的肼衍生物,并随后测试它们通过靶向 HIV 衍生的逆转录酶抑制 HIV-RNA 聚合的能力。体外检测结果表明,与未经处理的逆转录酶的预量化值相比,由于逆转录酶活性受到抑制,病毒载量有所下降。在这五种化合物中,4-N,N-二甲基氨基苯甲醛肼(C18H22N4)抑制 HIV-RT 的能力最强。N,N-二甲基氨基苯甲醛肼(C18H22N4)可以抑制 HIV-RT 的活性,而且随着化合物浓度的增加,这种效果会变得更加明显。
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In-Vitro Study of HIV-derived Reverse Transcriptase Inhibition
HIV utilizes a reverse transcriptase (RT) enzyme to convert the HIVRNA into DNA. Inhibition of the reverse transcription mechanism of HIV-RT may serve as a potential therapeutic approach to impede the proliferation of HIV in those who are infected. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are a type of medication that directly and non-competitively bind to the allosteric site of HIV-RT, inhibiting its polymerase activity. This study was aimed at the synthesis of hydrazine derivatives and their evaluation for HIV- reverse transcriptase inhibition using RT-qPCR-based assay. The objective of this study was to determine the HIV- reverse transcriptase inhibition using chemical compounds as non-nucleoside reverse transcriptase inhibitors in RT-qPCR. This study involved the synthesis of five distinct hydrazine derivatives, which were subsequently tested for their capacity to inhibit HIV-RNA polymerization by targeting HIVderived reverse transcriptase. For the determination of the study assay, commercially available HIV-RT was subjected to treatment with derivatives and utilized in an RT-qPCR experiment to determine the activity or inhibitory effects of HIV-RT for HIV-RNA polymerization. The in-vitro assay results demonstrated a reduction in viral load due to suppression of reverse transcriptase activity when compared to the pre-quantified values obtained from untreated RT. Among the five compounds, 4-N, N-dimethylamino benzaldehyde hydrazine (C18H22N4) had the highest ability to suppress HIV-RT. This molecule reduced HIV-RNA reverse transcription by more than 90% during RT-qPCR, which is a novel and promising strategy. N, N-dimethylamino benzaldehyde hydrazine (C18H22N4) can suppress the activity of HIV-RT, and this effect becomes more pronounced as the concentration of the compound increases.
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来源期刊
Anti-Infective Agents
Anti-Infective Agents Pharmacology, Toxicology and Pharmaceutics-Pharmacology
CiteScore
1.50
自引率
0.00%
发文量
47
期刊介绍: Anti-Infective Agents publishes original research articles, full-length/mini reviews, drug clinical trial studies and guest edited issues on all the latest and outstanding developments on the medicinal chemistry, biology, pharmacology and use of anti-infective and anti-parasitic agents. The scope of the journal covers all pre-clinical and clinical research on antimicrobials, antibacterials, antiviral, antifungal, and antiparasitic agents. Anti-Infective Agents is an essential journal for all infectious disease researchers in industry, academia and the health services.
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