SYNTHESIS & PHARMACOLOGICAL EVAL OF FLAVONES AS ANTI HIV AGENTS

合成

• 批准号: 6205916
• 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: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6205916
• 关键词: communicable diseases; 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(AIDS)的病原体有 导致了巨大的努力，以揭开病毒的基本行动 分子水平。潜在干预的各种目标 文献中已经概述了艾滋病毒的繁殖。必需品 病毒的繁殖和传播步骤涉及到反向 利用该酶将逆转录病毒RNA转录为前病毒DNA 逆转录酶(RT)。另一个有希望的可能性是 中断病毒生命周期的是使用抑制病毒的 病毒编码的蛋白水解酶，是病毒成熟所必需的。 HIV-1整合酶介导逆转录的整合 病毒DNA进入宿主基因组，是病毒生命周期中必不可少的一步 病毒。HIV整合酶是一种非固有的 代理商发展的东道主和诱人的目标 对抗艾滋病。HIV整合酶已被否定为 相当长的一段时间；最近的事态发展。我们现在建议 多种多羟基杂环芳香族化合物的合成， 有几个具有二级不饱和度，而一个大的 具有类黄酮类结构的品种。已知类黄酮类 槲皮素和咖啡酸苯乙基醚等结构 (CAPE)对肿瘤细胞和HIV具有细胞毒性 病毒。我们现在建议进行研究，以开发 CAPE基化合物AS的构效关系(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同意 对我们的化合物进行体外抗HIV活性筛选。