NONPARASITIC DRUG DISCOVERY AND DEVELOPMENT

非寄生虫药物的发现和开发

• 批准号: 6206678
• 负责人: BRIAN G SCHUSTER
• 金额: $ 7.8万
• 依托单位: WALTER REED ARMY INSTITUTE OF RESEARCH
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6206678
• 关键词: Africa; antibiotics; antifungal agents; antineoplastics; antiviral agents; bioassay; central nervous system disorders; cooperative study; cystic fibrosis; drug discovery /isolation; drug screening /evaluation; enzyme activity; medicinal plants; molecular biology; plant extracts; tissue /cell culture; training; tuberculosis

This associate program will provide evaluation of plant extracts and isolated pure compounds for antiviral, anti-cancer, antibacterial, and antifungal activities, CNS and cardiovascular activities, Cystic Fibrosis, Opportunistic infections, Anti-tuberculosis and biochemical and secondary enzyme based evaluation. The AP will also undertake studies and development of Phytomedicines as well as training in host countries. The antiviral assays will be conducted at Southern Research Institute (SRI), Alabama; anti-tumor evaluation at the University of Utah; CNS activity assays will be based at University of Miami and the Cystic Fibrosis screen at Florida State University. The National Institute of Allergy and Infectious Disease will screen samples for Opportunistic infections while MDS Panlabs will conduct biochemical and enzyme induced assays. Phytomedicine development will be conducted in ICBG laboratories in source countries. The high-volume antiviral pre-screen available at SRI will accommodate the evaluation of approximately 100-200 submitted test materials (natural product extracts/chemical compounds) per year for five years. The anti- tumor test system will include an activity screen using Chinese hamster ovary cell lines as secondary assay for extracts and active fractions. The assays will include a line that is sensitive to killing by agents that produce DNA double strand breaks of topoisomerase II inhibitors and tubulin inhibitors, another line that is sensitive to killing by some alkylating agents, and the third line will be from those that are sensitive to killing by some alkylating agents, and the third line will be from those that are sensitive to bulky DNA adducts such as melphalan or mitomycin C. Enhanced toxicity of an unknown drug towards any of these lines, therefore, will not only suggest a DNA directed mechanism, but suggest the mechanism by which that DNA damage is produced. The third assay under this Associate Program will be the neurochemical and radio- receptor assays which is suitable for high throughput screening for drug discovery and rapid biological profiling of natural products. Research developments in basic preclinical and clinical Neuroscience have catalyzed unprecedented efforts towards the discovery and development of novel CNS drugs which should prove effective for the treatment of neuropsychiatric diseases. The Cystic Fibrosis assays will screen plant material for compounds active in increasing the function of chimeric cystic fibrosis transmembrane conductance regulator (CFTR) reporter gene in yeast. The MDS Panlab will conduct various biochemical and enzyme mechanism based assays aimed at identifying isolated compounds from plant extracts that were found active in the automated receptor-binding assay. The International Centre for Ethnomedicine and Drug Development (Inter-CEED) will coordinate the development and standardization of Phytomedicines and Nigeria in collaboration with select pharmaceutical companies.

该副计划将提供植物提取物和 分离出抗病毒、抗癌、抗菌等纯化合物 抗真菌活性、中枢神经系统和心血管活性、囊性纤维化、 机会性感染、抗结核及生化及继发性 基于酶的评价。美联社还将开展研究和 植物药物的开发以及东道国的培训。这 抗病毒检测将在南方研究所（SRI）进行， 阿拉巴马州；犹他大学抗肿瘤评估；中枢神经系统活动 检测将基于迈阿密大学和囊性纤维化筛查 在佛罗里达州立大学。美国国家过敏症研究所 传染病将筛查样本中的机会性感染，同时 MDS Panlabs 将进行生化和酶诱导检测。 植物药开发将在ICBG来源实验室进行 国家。 SRI 提供的大容量抗病毒预筛将适应 评估大约 100-200 份提交的测试材料（天然材料） 产品提取物/化合物）每年每年一次，持续五年。反 肿瘤测试系统将包括使用中国仓鼠的活动筛选 卵巢细胞系作为提取物和活性组分的二次测定。这 检测将包括一条对以下试剂杀死敏感的细胞系： 产生拓扑异构酶 II 抑制剂的 DNA 双链断裂， 微管蛋白抑制剂，另一种对某些杀伤敏感的细胞系 烷化剂，第三行将来自那些 对某些烷化剂的杀伤敏感，第三线将是 来自那些对大体积 DNA 加合物敏感的人，例如美法仑或 丝裂霉素 C. 未知药物对其中任何一种的增强毒性 因此，线不仅表明 DNA 定向机制，而且 揭示了 DNA 损伤产生的机制。第三个 该副计划下的测定将是神经化学和放射- 适合高通量药物筛选的受体测定 天然产物的发现和快速生物学分析。研究 基础临床前和临床神经科学的发展促进了 为发现和开发新型中枢神经系统做出了前所未有的努力 应该证明对治疗神经精神疾病有效的药物 疾病。囊性纤维化检测将筛选植物材料 具有增强嵌合囊性纤维化功能活性的化合物 酵母中的跨膜电导调节器（CFTR）报告基因。 MDS Panlab 将进行各种基于生化和酶机制的检测 旨在从植物提取物中鉴定分离的化合物 在自动受体结合测定中发现具有活性。国际 民族医学和药物开发中心 (Inter-CEED) 将协调 尼日利亚植物药的开发和标准化 与选定的制药公司合作。