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.

这项助理计划将提供对植物提取物和 分离纯化的化合物用于抗病毒、抗癌、抗菌和 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、生化和继发性感染 以酶为基础的评价。美联社还将进行研究和 开发植物医药以及在东道国进行培训。这个 将在南方研究所(SRI)进行抗病毒检测， 阿拉巴马州；犹他大学的抗肿瘤评估；中枢神经系统活动 化验将在迈阿密大学和囊性纤维化筛查进行 在佛罗里达州立大学。美国国家过敏症和过敏研究所 传染病将对样本进行机会性感染筛查，而 MDS PanLabs将进行生化和酶诱导分析。 植物药物开发将在ICBG实验室进行源代码 国家。 SRI提供的大容量抗病毒预筛查将容纳 对大约100-200份提交的测试材料进行评估(自然 产品提取物/化合物)，为期五年。反- 肿瘤测试系统将包括使用中国仓鼠的活动屏幕 卵巢细胞系作为萃取物和活性部位的二次测定。这个 化验将包括一条对以下特工的杀戮敏感的行 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，另一种对某些人的杀戮敏感的产品 烷基化试剂，第三行将来自那些 对某些烷基化试剂的杀灭敏感，第三行将是 来自对大体积DNA加合物敏感的DNA加合物，如马法兰或 丝裂霉素C增强一种未知药物对上述任何一种药物的毒性 因此，LINES不仅提出了一种DNA引导的机制，而且 暗示了造成DNA损伤的机制。第三 在这项联合计划下的化验将是神经化学和放射性- 适用于药物高通量筛选的受体分析方法 天然产物的发现和快速生物图谱分析。研究 基础基础神经科学和临床神经科学的发展促进了 为发现和发展新型中枢神经系统所做的前所未有的努力 应证明对治疗神经精神疾病有效的药物 疾病。囊性纤维化分析将筛选植物材料 具有增强嵌合性囊性纤维化功能的化合物 酵母跨膜电导调节蛋白报告基因。MDS PanLab将进行各种基于生化和酶机制的分析 旨在从植物提取物中鉴定分离出的化合物 在自动受体结合分析中发现具有活性。《国际邮报》 民族医药和药物开发中心将协调 年植物医学和尼日利亚的发展和标准化 与精选的制药公司合作。