SYNTHESIS & PHARMACOLOGICAL EVAL OF FLAVONES AS ANTI HIV AGENTS

点击翻译按钮获取中文摘要

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.