Isolation Chemistry of Tropical Plants and Biological Evaluation

俄亥俄州立大学 (OSU) 的项目 1 由分离化学、去重复和 生物测试组件。具体目标 1-4 将涉及： (a) 制备所有主要植物的提取物 主要由项目 2（伊利诺伊大学芝加哥分校，UIC）提供的材料用于初始生物 筛查； (b) 初步筛选后对活性先导进行 LC-MS 去重复研究（以便 优先考虑样品以进行活动引导的分级分离）； (c) 使用色谱法的纯化程序 方法（由计划项目中的内部生物测定法和其他地方的生物测定法指导）；和（四） 分别进行化合物结构阐明。生物活性化合物的结构将被确定 使用现代光谱方法，以化学转化和 X 射线晶体学为支持 [要执行的工作项目 1、2 以及核心 B (OSU) 的药物化学部分]，其中 必要的。在具体目标 5 中，植物提取物将针对一小部分样本进行初步筛选。 核心 A (UIC) 的癌细胞。然后将感兴趣的摘录提交到项目 1 (OSU) 中进行测试， 项目 3 [哥伦比亚大学通过北卡罗来纳大学格林斯伯勒分校 (UNCG)]，以及一个新项目 制药合作伙伴，卫材公司，安多弗，马萨诸塞州（通过 OSU 的 Core C）}：项目 1 生物测定将 涉及针对 OSU-CLL（慢性淋巴细胞白血病）和 OSU-NB（正常 B 细胞）细胞系的测试， 以及来自俄勒冈州立大学詹姆斯癌症医院 CLL 患者的原发肿瘤样本。测试还将 通过三种内部机制测定进行[即核因子-κB (NF-κB)、线粒体跨膜 电位（MTP）抑制和Semaphorin-3]。项目 1 的活性化合物也将在 UIC（核心 A）、哥伦比亚大学（项目 3）和卫材公司提供体外生物测试系统。 （通过核心 C），在核心 A 和 C 的体内测定中也对有前景的化合物进行了评估。 将与项目 1 中的有希望的先导化合物进行体外合作和测试 奥霍州立大学韦克斯纳医学中心 (OSUWMC) 的同事。在具体目标 6 中，扩大规模 根据程序需要进行分离，也可以通过合成进行化合物放大 与 Core B 合作。将努力开发新的生物活性化合物 作为潜在抗癌化合物的临床前评估。

Project 1 at The Ohio State University (OSU) is comprised of isolation chemistry, dereplication, and biological testing components. Specific Aims 1-4 will involve: (a) preparing extracts of all primary plant materials provided mainly from Project 2 (University of Illinois at Chicago, UIC) for initial biological screening; (b) LC-MS dereplication studies on active leads following preliminary screening (in order to prioritize samples for activity-guided fractionation); (c) purification procedures using chromatographic methods (guided by both in-house bioassays and those elsewhere, in the program project); and (d) compound structure elucidation, respectively. The structures of bioactive compounds will be determined using modern spectroscopic methods, backed up by chemical transformations and X-ray crystallography [work to be performed Projects 1, 2, and the medicinal chemistry portion of Core B (OSU)], where necessary. In Specific Aim 5, plant extracts will be subjected to primary screening against a small panel of cancer cells at Core A (UIC). Extracts of interest will then be submitted for testing in Project 1 (OSU), Project 3 [Columbia University via the University of North Carolina at Greensboro (UNCG)], and a new pharmaceutical partner, Eisai Inc., Andover, MA (through Core C at OSU)}: The Project 1 bioassays will involve testing against the OSU-CLL (chronic lymphocytic leukemia) and OSU-NB (normal B-cell) cell lines, and against primary tumor samples from CLL patients at the OSU James Cancer Hospital. Testing will also occur with three in-house mechanistic assays [viz., nuclear factor-κB (NF-κB), mitochondrial transmembrane potential (MTP) inhibition, and Semaphorin-3]. Active compounds from Project 1 will also be tested in the in vitro biological test systems available at UIC (Core A), Columbia University (Project 3), and Eisai Inc. (through Core C), with promising compounds also evaluated in in vivo assays in Cores A and C. Collaborative in vitro and testing on promising lead compounds from Project 1 will be performed with colleagues at The Oho State University Wexner Medical Center (OSUWMC). In Specific Aim 6, scale-up isolations when required by programmatic needs, with compound scale up also conducted by synthesis in collaboration with Core B. Stringent efforts will be made to progress new bioactive compounds towards preclinical evaluation as potential anticancer compounds.