吲哚衍生物RJQ系列抗HIV-1活性及作用机制研究

HIV逆转录抑制剂是最早应用于临床的抗HIV的药物，一直都是研究抗HIV药物的重要靶点，也是目前抗HIV药物研究的热点之一。然而这些抗逆转录的药物作用于逆转录的过程不十分明确，并且由于HIV逆转录过程极易产生突变，使这类药物产生严重的耐药性，疗效减弱。申请人前期研究发现吲哚衍生物RJQ-c, j, l, n具有非常好的抗HIV活性，并且初步研究发现它们是通过抑制HIV逆转录来发挥其抗HIV活性。本项目基于前期研究工作基础拟在通过对这一系列化合物的抗HIV活性进行研究，采用分子对接技术和荧光定量PCR对RJQ-c, j, l, n逆转录机制进行检测，并通过体外诱导HIV耐药株对这类化合物的作用机制进行分析研究，为我国开发新的高效低毒，克服耐药性的新的非核苷类的HIV逆转录抑制剂的设计合成提供思路。

HIV reverse transcriptase inhibitor is used in the clinical treatment firstly. It was always an important target of anti-HIV drugs; furthermore, it is currently one of the research interests in anti-HIV drug; however, the target of these drugs, is not very clear. Moreover the HIV reverse transcriptase can easily mutate, thence these drugs would produce serious drug-resistance, treatment ineffective. It has been found that indole derivativesRJQ-c, j, l, n show very effective anti-HIV activities in preliminary study. The preliminary study found that they inhibit HIV replication through inhibiting the HIV reverse process. The project is based on preliminary studies, using molecular docking and qPCR to detect the mechanisms of indole derivatives RJQ-c, j, l, n to inhibit reverse transcriptase replication and induce HIV resistant strains in vitro to study the mechanisms. The study would provide new ideas for the development of new non-nucleoside HIV reverse transcriptase inhibitors with high-efficiency, low toxicity and without resistance.