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Identification of anti-HIV agent(s) from Sophora Alkaloids

苦参生物碱中抗 HIV 药物的鉴定

基本信息

批准号：
7494340
负责人：
LI HUANG
金额：
$ 19.2万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-04-01 至 2010-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7494340
关键词：
2-cyclopentyl-5-(5-isoquinolylsulfonyl)-6-nitro-1H-benzo(D)imidazole AIDS therapy Acquired Immunodeficiency Syndrome Adverse effects Alkaloids Anti-HIV Agents Anti-Inflammatory Agents Anti-inflammatory Biological Factors China Chinese Herbs Chinese People Chinese Traditional Medicine Communicable Diseases Coumarins Country Development Drug usage Drug-sensitive Effectiveness Escape Mutant Flavonoids Fractionation Genotype Goals HIV HIV-1 Herbal Medicine Highly Active Antiretroviral Therapy Inhibitory Concentration 50 Lead Malignant Neoplasms Medicine Modern Medicine Morbidity - disease rate Multi-Drug Resistance Patients Phase Public Health RNA-Directed DNA Polymerase Reporting Screening procedure Severe Acute Respiratory Syndrome Sophora Testing Viral Virus Virus Diseases alpha benzopyrone base drug development improved mortality novel pandemic disease small molecule

项目摘要

DESCRIPTION (provided by applicant): Highly active anti-retroviral therapy has successfully reduced the morbidity and mortality of AIDS patients. However, the side effects associated with long term drug usage and the emerging of multi-drug resistance viruses have undermined the effectiveness of current treatment. Therefore, new anti-HIV-1 agents with novel mechanism of action have the potential to improve current AIDS therapy. The goal of this study is to identify novel anti-HIV-1 agents from traditional Chinese herb medicines. We have screened many Chinese medicines for anti-HIV activity and found one that possessed potent anti-HIV activity. This anti-HIV Chinese medicine, Sophora Alkaloids Tannate (SAT), was used widely for its anti-inflammatory activity as an over the counter medicine in China. We hypothesized that SAT contains one or several anti-HIV compounds that can inhibit HIV-1 replication. This hypothesis will be tested by pursuing the following specific aims: 1. Identify the active components in SAT that are responsible for the anti-HIV activity. 2. Determine the mechanisms of anti-HIV-1 action of each active compound in SAT. Results derived from this study are expected to provide useful information to determine whether the anti-HIV compounds isolated from SAT has the potential to be developed into anti-HIV drugs for AIDS therapy. PUBLIC HEALTH RELEVANCE: The objective of this R21 application is to identify the active component(s) from a Chinese traditional herbal medicine "Sophora Alkaloids Tannate" that has shown potent anti-HIV activity.

描述(申请人提供)：高效抗逆转录病毒疗法成功降低了艾滋病患者的发病率和死亡率。然而，与长期用药相关的副作用和多药耐药病毒的出现破坏了当前治疗的有效性。因此，具有新作用机制的新型抗HIV-1药物具有改善当前艾滋病治疗的潜力。本研究的目的是从传统中草药中寻找新的抗HIV-1药物。我们筛选了许多具有抗艾滋病毒活性的中药，发现了一种具有强大抗艾滋病毒活性的中药。苦豆碱单宁酸酯(SAT)是一种抗艾滋病毒的中药，在中国的非处方药中因其抗炎活性而被广泛使用。我们假设SAT含有一种或几种能抑制HIV-1复制的抗HIV化合物。这一假说将通过追求以下具体目标来验证：1.确定SAT中负责抗HIV活性的活性成分。2.确定SAT中各活性成分的抗HIV-1作用机制。这项研究的结果有望提供有用的信息，以确定从SAT中分离出的抗HIV化合物是否有潜力开发成用于艾滋病治疗的抗HIV药物。公共卫生相关性：这项R21应用的目的是从一种具有强大抗艾滋病毒活性的中草药“苦豆碱单宁酸酯”中鉴定活性成分(S)。