NONPARASITIC DRUG DISCOVERY AND DEVELOPMENT

非寄生虫药物的发现和开发

• 批准号: 6358149
• 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/6358149
• 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.

该助理计划将对植物提取物进行评估和 用于抗病毒，抗癌，抗菌和的隔离纯化合物 抗真菌活动，中枢神经系统和心血管活动，囊性纤维化， 机会性感染，抗结核和生物化学和继发性 基于酶的评估。美联社还将进行研究， 植物医学的发展以及东道国的培训。这 抗病毒测定将在南方研究所（SRI）进行 阿拉巴马州；犹他大学的抗肿瘤评估；中枢神经系统活性 测定将位于迈阿密大学和囊性纤维化屏幕 在佛罗里达州立大学。美国国家过敏研究所 传染病将筛选样品以获取机会性感染，而 MDS PANLABS将进行生化和酶诱导的测定。 植物医学的开发将在冰BG实验室中进行。 国家。 SRI提供的大批量抗病毒预屏幕可容纳 评估大约100-200个提交的测试材料（自然的测试材料 产品提取物/化合物）每年五年。反 - 肿瘤测试系统将使用中国仓鼠进行活动屏幕 卵巢细胞系作为提取物和活性分数的次要测定。这 测定将包括一条对被代理杀死敏感的行 产生拓扑异构酶II抑制剂的DNA双链断裂和 微管蛋白抑制剂，这是对某些人杀死敏感的另一条线 烷基化剂，第三行将来自 对某些烷基化剂杀死敏感，第三行将 从对大笨重的DNA加合物（例如Melphalan或 丝裂霉素C.未知药物对任何一种的毒性增强 因此，线不仅建议DNA定向机制，而且还会提出 建议产生DNA损伤的机制。第三 根据该助理程序的测定将是神经化学和无线电 适用于药物高通量筛查的受体测定 天然产物的发现和快速生物学分析。研究 基本临床前和临床神经科学的发展已经催化 为发现和发展新颖中枢神经系统的空前努力 应该证明有效治疗神经精神病学的药物 疾病。囊性纤维化测定将筛选植物材料 活跃于增加嵌合囊性纤维化功能的化合物 酵母中的跨膜电导调节剂（CFTR）报告基因。 MDS PANLAB将进行各种基于生化和酶机制的测定 旨在从植物提取物中鉴定出孤立的化合物 发现在自动受体结合测定中活跃。国际 民族医学和药物开发中心（共同）将协调 植物医学和尼日利亚的发展和标准化 与精选制药公司合作。