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NONPARASITIC DRUG DISCOVERY AND DEVELOPMENT

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
依托单位国家:
美国
项目类别:
财政年份:
1999
资助国家:
美国
项目状态:
已结题
起止时间:
1999-09-30 至 2000-09-29

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中文摘要
翻译
该项目将提供植物提取物的评估, 用于抗病毒、抗癌、抗菌和抗微生物的分离的纯化合物, 抗真菌活性,CNS和心血管活性,囊性纤维化, 细菌感染、抗结核和生化及继发性 基于酶的评价AP还将进行研究, 植物医学的发展以及在东道国的培训。的 抗病毒试验将在南方研究所(SRI)进行, 亚拉巴马;犹他州大学的抗肿瘤评价; CNS活性 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。国家过敏症研究所和 传染病部将对样本进行细菌感染筛查, MDS Panlabs将进行生化和酶诱导试验。 植物药的开发将在ICBG实验室进行, 国家 SRI提供的高容量抗病毒预筛选将适应 评估大约100-200份提交的测试材料(天然 产品提取物/化学化合物)。反- 肿瘤试验系统将包括使用中国仓鼠的活性筛选 卵巢细胞系作为提取物和活性级分的次级测定。的 测定将包括对被试剂杀死敏感的线, 产生拓扑异构酶II抑制剂的DNA双链断裂, 微管蛋白抑制剂,另一种对某些细胞的杀伤敏感的抑制剂 烷基化剂,第三线将来自那些 对某些烷化剂的杀伤敏感,第三线将是 从那些对庞大的DNA加合物如美法仑或 丝裂霉素C一种未知药物对这些药物的毒性增强 因此,线不仅表明DNA指导的机制, 表明了DNA损伤产生的机制。第三 在这个副计划下的分析将是神经化学和无线电- 受体测定法,其适用于药物的高通量筛选 天然产物的发现和快速生物特征分析。研究 基础临床前和临床神经科学的发展 为发现和开发新型CNS做出了前所未有的努力 应被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, 具有增加嵌合囊性纤维化功能活性的化合物 酵母中的跨膜传导调节因子(CFTR)报告基因。所述MDS Panlab将进行各种基于生化和酶机制的分析 目的是从植物提取物中分离出化合物, 在自动受体结合试验中发现有活性。国际 民族医学和药物开发中心将协调 植物医学的发展和标准化与尼日利亚 与精选的制药公司合作。
英文摘要
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.
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NONPARASITIC DRUG DISCOVERY AND DEVELOPMENT
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