DRUG DISCOVERY FROM PLANTS OF VIETNAM AND LAOS FOR AIDS AND MALARIA THERAPIES

联合项目-3(AP-3)的主要目标是分离和 确定HIV复制的特定抑制剂和有效的抗HIV药物 抗氯喹恶性疟原虫。它将提供生物检测 支持发现有效防治疟疾的天然产物 和艾滋病通过对大约500种植物提取物的筛选 每年进行生物活性分级程序。来源 评估材料将在和LAO项下挑选和收集 中国人民民主共和国。主要基于生物多样性的选择 将采用方法，尽管可能采用民族植物学调查。 在有限的范围内。该项目还将执行初始提取 植物材料和已确认的活性植物化学物质的放大分离。 将使用光谱和化学方法来确定 纯生物活性化合物的结构。将努力最大限度地减少 已知的抗HIV或抗疟疾化合物的重新分离 文献中的性质(NAPRALERT)和LC/MS/MS衍生化 技巧。此外，几种HIV-1抑制剂逆转了 转录酶(RT)和许多有希望的抗疟疾化合物和 提取物是通过正在进行的合作药物发现而确定的 与越南的研究人员共同努力。这些具有生物活性的天然 产品将被重新隔离，并在更复杂的生理条件下进行评估 生物分析系统和相关的机械分析，以确定优先顺序 用于更高级的体内研究。在与葛兰素史克的合作中， 活性化合物将作为药物开发的候选药物进行评估。 或者，新的分离物可以被认为是新的线索 选择性抑制剂的开发。

The major objective of Associate Project-3 (AP-3) is to isolate and identify specific inhibitors of HIV replication and agents active against chloroquine-resistant Plasmodium falciparum. It will provide bioassay support for the discovery of natural products effective against malaria and AIDS through the screening of approximately 500 plant extracts annually followed by bioactivity fractionation procedures. Source materials for evaluation will be selected and collected under and Lao People's Democratic Republic. A primarily biodiversity-based selection approach will be adopted, although ethnobotanical inquiry may be employed to a limited extent. This project will also perform initial extraction of plant materials and scale-up isolation of confirmed active phytochemicals. Spectroscopic and chemical methods will be used to determine the structures of pure bioactive compounds. Efforts will be made to minimize the re-isolation of compounds with known anti-HIV or anti-malarial properties through literature (NAPRALERT) and LC/MS/MS dereplication techniques. Additionally, several inhibitors of HIV-1 reverse transcriptase (RT) and numerous promising anti-malarial compounds and extracts have been identified through ongoing collaborative drug discovery efforts with researchers in Vietnam. These biologically active natural products will be re-isolated and evaluated in more physiologically complex bioassay systems and relevant mechanistic assays in order to prioritize them for more advanced in vivo studies. In concert with Glaxo Wellcome, active compounds will be evaluated as candidates for development as drugs. Alternatively, novel isolates may be considered as new leads for the development of selective inhibitors.