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、去复制和 生物检测组件。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)提供的初始生物学材料 筛选；(B)初步筛选后活性导联的LC-MS去复制研究(以便 (C)使用层析进行纯化程序 方法(由内部生物测定和方案项目中其他地方的生物测定指导)；和(D) 分别对化合物结构进行了解析。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射线结晶学为支持 [项目1、2和核心B的药物化学部分(OSU)]，其中 这是必要的。在具体目标5中，将对植物提取物进行初步筛选，以防止 位于核心A的癌细胞(UIC)。感兴趣的摘录随后将在项目1(OSU)中提交测试， 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(UNG)]，以及一个新的 制药合作伙伴，卫材公司，马萨诸塞州安多弗(通过OSU的Core C)}：项目1生物检测将 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， 以及来自俄亥俄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 通过三种内部机制分析[即核因子-κB(核因子-κB)、线粒体跨膜 电位(MTP)抑制和信号素-3]。来自项目1的活性化合物也将在IN进行测试 UIC(Core A)、哥伦比亚大学(Project 3)和卫材(Eisai Inc.)提供体外生物学测试系统。 (通过核心C)，有前景的化合物也在A和C核心的体内试验中进行了评估。 项目1中有希望的先导化合物的体外合作和测试将与 俄亥俄州立大学韦克斯纳医学中心(OSUWMC)的同事们。具体目标6，扩大规模 在编程需要时进行隔离，还可以通过在 与核心B的合作将作出严格努力，以取得新的生物活性化合物的进展，以期 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.