SYNTHESIS & PHARMACOLOGICAL EVAL OF FLAVONES AS ANTI HIV AGENTS

合成

• 批准号: 6358114
• 负责人: KINFE KEN REDDA
• 金额: $ 8.08万
• 依托单位: FLORIDA AGRICULTURAL AND MECHANICAL UNIV
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6358114
• 关键词: AIDS; biotechnology; communicable diseases; enzymes; genome; immunology; inflammation; lymphatic system; minority institution research support; pharmacology; virus

The discovery of the human immunodeficiency virus (HIV) as the causative agent of the acquired immunodeficiency syndrome (AIDS) has led to enormous efforts to unravel the basic actions of the virus at a molecular level. A variety of targets for potential intervention of HIV multiplication have been outlined in the literature. An essential step for the multiplication and spread of the virus involves reverse transcription of the retroviral RNA to proviral DNA by the enzyme reverse transcriptase (RT). Another promising possibility for interrupting the viral life cycle is the use of inhibitors of the virally encoded protease which is indispensable for viral maturation. The HIV-1 integrase enzyme mediates integration of reverse-transcribed viral DNA into the host genome, an essential step in the life cycle of the virus. The HIV integrase enzyme which is not indigenous to the host presents and attractive target for the development of agents against AIDS. The HIV integrase has been negl ected as a target for quite a long time until; recent developments. We now propose the synthesis of many polyhydroxylated heterocyclic aromatic compounds, with several having secondary degrees of unsaturation and a large variety bearing a flavonoid structure. It is known that flavonoid structures, such as quercetin and caffeic acid phenylethyl ether (CAPE) exhibit cytotoxicity towards tumor cells as well as the HIV virus. We now propose to undertake studies to develop structure-activity relationship (SAR) data on CAPE based compounds as HIV integrase inhibitors. NIH's National Cancer Institute has agreed to conduct in vitro screening for anti-HIV activity for our compounds.

人类免疫缺陷病毒（HIV）的发现， 获得性免疫缺陷综合征（艾滋病）的病原体 导致了巨大的努力，以解开病毒的基本行动， 分子水平。 各种可能干预的目标 文献中已经概述了艾滋病毒的繁殖。 一个基本 病毒增殖和传播的一个步骤涉及逆转 通过酶将逆转录病毒RNA转录为前病毒DNA 逆转录酶（RT）。 另一个有希望的可能性， 中断病毒的生命周期是使用抑制剂， 病毒编码的蛋白酶，其是病毒成熟所必需的。 HIV-1整合酶介导逆转录的 病毒DNA进入宿主基因组，这是病毒生命周期中的重要一步。 病毒 HIV整合酶不是固有的， 主办方提出了有吸引力的代理开发目标 对抗艾滋病。 HIV整合酶已被认为是 很久以前;最近的发展。 我们现在建议 许多多羟基杂环芳香化合物的合成， 其中几种具有次级不饱和度， 具有类黄酮结构的变种。 据了解，类黄酮 结构，如槲皮素和咖啡酸苯乙醚 （CAPE）对肿瘤细胞以及HIV表现出细胞毒性， 病毒 我们现建议进行研究， 基于CAPE的化合物的结构-活性关系（SAR）数据， HIV整合酶抑制剂。 美国国立卫生研究院国家癌症研究所已经同意 对我们的化合物进行抗HIV活性的体外筛选。