NEW DRUGS FOR OPPORTUNISTIC INFECTIOUS DISEASES

治疗机会性传染病的新药

• 批准号: 3141177
• 负责人: ALICE M. CLARK
• 金额: $ 11.01万
• 依托单位: UNIVERSITY OF MISSISSIPPI
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3141177
• 关键词: Actinomycetales infection; Cryptococcus neoformans; Mycobacterium smegmatis; antibacterial agents; antifungal agents; bioassay; cryptococcosis; disease /disorder model; drug adverse effect; laboratory mouse; microorganism disease chemotherapy; nonhuman therapy evaluation; opportunistic infections; plant extracts

Acquired immunodeficiency Syndrome (AIDS) is characterized by a breakdown in the immune system which is manifested in the form of serious opportunistic infections. Treatment of such infections is often inadequate for a variety of reasons, including the lack of effective antimicrobial therapy. The opportunistic infections most commonly associated with AIDS are parasitic (pneumocystosis, toxoplasmosis, cryptosporidiosis), fungal (candidiasis, cryptococcosis), bacterial (mycobacteriosis), and viral (herpes simplex and cytomegalovirus). Historically, most bacterial infections and localized fungal infections have been effectively treated with one of the numerous clinically available antibiotics. However, the need for new, more effective and less toxic antibiotics for the treatment of disseminated fungal and mycobacterial infections is obvious in light of the significant toxicities and failure rates of the currently available agents. The discovery of new antibiotics has in the past successfully relied primarily upon the isolation of such agents form natural sources. The major advantage of this approach over chemical synthesis or modification of existing agents is the likelihood of identifying new prototype drugs with quite different chemical structures, and hence, less likelihood of similar toxicities and cross-resistance. Although microorganisms have traditionally served as the primary source of new antibiotics, it has recently been shown that higher plants also serve as sources for a number of diverse antimicrobial agents. The objective of this project is to discover new prototype antibiotics with potential utility specifically for the treatment of opportunistic disseminated mycoses and mycobacteriosis. This goal will be accomplished by the initial in vitro evaluation of antifungel and antimycobacterial activity of extracts of higher plants. Plant extracts which show good activity will be fractionated and purified using a bioassay-directed scheme. This approach ensures that relatively little time and effort will be wasted in isolating inactive materials. Pure active compounds with significant minimum inhibitory concentrations (MIC) will be evaluated for in vivo efficacy in established animal models of disseminated mycosis and mycobacteriosis in order to determine their potential clinical utility.

获得性免疫缺陷综合症（艾滋病）的特点是 免疫系统崩溃，表现为 严重的机会性感染。 此类感染的治疗方法是 往往由于各种原因而不够充分，包括缺乏 有效的抗菌治疗。 机会性感染最多 通常与艾滋病相关的是寄生虫（肺囊虫病、 弓形体病、隐孢子虫病）、真菌病（念珠菌病、 隐球菌病）、细菌性（分枝杆菌病）和病毒性（疱疹） 单纯形病毒和巨细胞病毒）。 从历史上看，大多数细菌感染和局部真菌感染 感染已通过众多方法之一得到有效治疗 临床上可用的抗生素。 然而，需要新的、更多的 有效且毒性较小的抗生素用于治疗 播散性真菌和分枝杆菌感染在 鉴于显着的毒性和失败率 目前可用的代理。 新抗生素的发现 过去成功主要依靠隔离 这些物质是天然来源。 这样做的主要优点 化学合成或现有试剂改性的方法 是鉴定新原型药物的可能性 不同的化学结构，因此，不太可能 相似的毒性和交叉耐药性。 虽然微生物 传统上是新抗生素的主要来源， 最近的研究表明，高等植物也可以作为来源 用于多种不同的抗菌剂。 该项目的目标是发现新的原型 专门用于治疗的具有潜在效用的抗生素 机会性播散性真菌病和分枝杆菌病。 这 目标将通过初步体外评估来实现 较高提取物的抗真菌和抗分枝杆菌活性 植物。 显示出良好活性的植物提取物将 使用生物测定指导方案进行分级和纯化。 这 方法确保相对较少的时间和精力 浪费在隔离非活性材料上。 纯活性化合物 显着的最低抑制浓度（MIC）将是 在已建立的动物模型中评估体内功效 播散性真菌病和分枝杆菌病以确定 他们潜在的临床效用。