THERAPIES FOR AIDS-RELATED OPPORTUNISTIC INFECTIONS

艾滋病相关机会性感染的治疗

• 批准号: 2070686
• 负责人: ALICE M. CLARK
• 金额: $ 34.54万
• 依托单位: UNIVERSITY OF MISSISSIPPI
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-01-15 至 1996-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2070686
• 关键词: AIDS therapy; cooperative study; microorganism disease chemotherapy; opportunistic infections

The overall goal of this group effort is to identify promising drug candidates for the therapy of Pneumoycstis carinii pneumonia and disseminated fungal infections in AIDS patients. We propose to accomplish this goal by investigating the mechanism(s) of action and structure activity relationships of new lead compounds already shown to be effective against the target Ol pathogens. These prototype compounds have demonstrated desirable biological activitaies, but virtually no SAR and/or mechanism of action information is available to direct future development efforts. Thus, we propose to investigate the mechanism(s) of action of selected novel fungicidal agents and pursue structure-activity relationship studies for three classes of agents with anti-Pneumocystis and/or antifungal activity. The research objectives of the Group are; . Investigate the mechanism(s) of action (MOA) of selected prototype fungicidal natural products. . Investigate the utility of in vitro assays to search for novel agents that act at potential new targets. . Investigate the role of primaquine-binding proteins in the MOA and clinical utility of 8-aminoquinolines and other antiPneumocystis drugs. . Explore the SAR of 8-aminoquinolines as anti-Pneumocystis agents. . Explore the SAR of two prototype fungicidal antibiotics. Thus, the Group will couple knowledge of the molecular basis of action with synthetic efforts to prepare improved analogs. Additionally, as a consequence of the investigation of the MOA of selected antifungal agents, it is likely that new molecular targets will be identified. As part of this effort, we also propose to develop rapid, reliable and convenient in vitro assays designed to detect novel selective antifungal activity based on specific mechanism(s) of action. Successful completion of the project should provide; . specific drug candidates for development as new therapies for treatment of AIDS related PCP and disseminated mycoses . identification of potential new targets . novel means of searching for new selective therapies in the future.

该小组努力的总体目标是确定有前途的药物 卡氏肺孢子虫肺炎治疗候选者 艾滋病患者的播散性真菌感染。 我们建议完成 通过研究作用机制和结构来实现这一目标 新先导化合物的活性关系已被证明是有效的 对抗目标O1病原体。 这些原型化合物具有 表现出理想的生物活性，但几乎没有 SAR 和/或 行动机制信息可用于指导未来的发展 努力。 因此，我们建议研究作用机制 筛选新型杀菌剂并探究构效关系 针对三类抗肺孢子虫药物和/或 抗真菌活性。 该小组的研究目标是： 。 研究所选原型的作用机制 (MOA) 天然杀真菌产品。 。 研究体外测定在寻找新药物中的效用 作用于潜在的新目标。 。 研究 MOA 和伯氨喹结合蛋白的作用 8-氨基喹啉类等抗肺孢子菌药物的临床应用。 。 探索 8-氨基喹啉作为抗肺孢子菌药物的比吸收率。 。 探索两种原型杀菌抗生素的比吸收率。 因此，该小组将把分子作用基础的知识与 制备改进类似物的合成努力。 此外，作为 对所选抗真菌药物的 MOA 进行研究的结果， 很可能会确定新的分子靶点。 作为一部分 为此，我们还建议开发快速、可靠、便捷的 旨在检测新型选择性抗真菌活性的体外测定 关于具体的作用机制。 项目顺利完成 应提供； 。 开发作为治疗新疗法的特定候选药物 艾滋病相关的 PCP 和播散性真菌病 。 确定潜在的新目标 。 未来寻找新的选择性疗法的新方法。