CHEMISTRY OF NATURAL PRODUCTS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。研究兴趣涉及天然产物化学的各个方面，包括其分离，结构测定，合成和生物活性。他的研究小组与人类学家、植物学家、药理学家和微生物学家合作，研究了来自巴基斯坦、玻利维亚和中国的特征药用植物，作为药物开发的先导化合物来源。这些活性化合物的分离涉及制备和分析色谱法，并通过抗癌、抗HIV、抗细菌、抗真菌、抗锥虫、杀虫和CNS活性的生物测定来指导。结构测定主要依赖于NMR、质谱、UV和IR方法。进行合成以提供用于生物评价的额外活性化合物，以确定结构-活性相关性，并使用适当的同位素标记来研究作用的生化机制。近年来发现并研究了几种具有抗癌、抗结核、特别是抗HIV活性的先导化合物。 最近的努力集中在研究最初在玻利维亚的卡拉瓦亚印第安人使用的几种药用植物中发现的具有抗艾滋病毒活性的化合物。从四种不同的植物中分离出的四种不同的活性化合物都被证明是奎尼酸[DCQA]的二咖啡酰衍生物。显著地，它们的抗HIV活性被证明是由于抑制整合酶，整合酶是三种已知病毒酶中唯一的一种[其他是逆转录酶和蛋白酶]，对此没有已知的药物。合成了一种DCQA的简单类似物菊苣酸[二咖啡酰酒石酸]，该化合物也被证明是HIV-1整合酶的选择性抑制剂，因此被选择作为先导化合物，用于通过抑制HIV整合酶来进行抗HIV活性的构效关系的持续合成研究。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Research interests involve all aspects of the chemistry of natural products including their isolation, structure determination, synthesis and biological activity. Working in collaboration with anthropologists, botanists, pharmacologists, and microbiologists his group examines characterized medicinal plants from Pakistan, Bolivia and China as sources of lead compounds for drug development. Isolation of these active compounds involves preparative and analytical chromatography and is directed by bioassays for anti-cancer, anti-HIV, anti-bacterial, anti-fungal, anti-trypanosomal, insecticidal and CNS activity. Structure determination relies heavily on NMR, mass spectral, UV and IR methods. Syntheses are undertaken to supply additional active compounds for biological evaluation, to determine structure-activity correlations and, with appropriate isotopic labeling, to study biochemical mechanisms of action. Several lead compounds with anti-cancer, anti-TB and, especially, anti-HIV activity have recently been found and studied. Recent efforts have centered on studies of compounds with anti-HIV activity originally detected in several medicinal plants used by the Kallawaya Indians of Bolivia. Four different active compounds isolated from four different plants all turned out to be dicaffeoyl derivatives of quinic acid [DCQA's]. Significantly their anti-HIV activity was shown to be due to the inhibition of integrase, the only one of three known viral enzymes [the others being reverse transcriptase and protease] for which no drugs were known. Chicoric acid [dicaffeoyltartaric acid], a simple analogue of DCQA, was synthesized, also shown to be a selective inhibitor of HIV-1 Integrase and therefore was chosen as the lead compound for an on-going synthetic study of the structure-activity relationships responsible for anti-HIV activity by inhibition of HIV-integrase.