NEW DRUGS FOR OPPORTUNISTIC INFECTIOUS DISEASES

获得性免疫缺陷综合征（艾滋病）的特征是 免疫系统的崩溃，表现为 严重的机会性感染。 这种感染的治疗是 由于各种原因，往往不充分，包括缺乏 有效的抗菌治疗。 机会性感染 通常与AIDS相关的是寄生虫（肺囊虫病， 弓形体病，隐孢子虫病），真菌（念珠菌病， 隐球菌病）、细菌性（分枝杆菌病）和病毒性（疱疹 单纯和巨细胞病毒）。 历史上，大多数细菌感染和局部真菌感染 感染已经得到了有效的治疗， 临床上可用的抗生素。 然而，需要新的，更多的 有效和毒性较小的抗生素，用于治疗 播散性真菌和分枝杆菌感染是明显的， 鉴于药物的显著毒性和失败率， 现有的代理商。 新抗生素的发现 在过去，成功地主要依赖于隔离， 这些试剂形成天然来源。 这样做的主要好处是 现有药剂的化学合成或改性方法 是用相当大的概率来识别新的原型药物， 不同的化学结构，因此， 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，高等植物也是 用于多种抗菌剂。 这个项目的目标是发现新的原型 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价来实现， 高等植物提取物的抗真菌和抗分枝杆菌活性 植物 表现出良好活性的植物提取物将是 使用生物测定指导的方案分级和纯化。 这 这种方法确保了相对较少的时间和精力， 浪费在分离非活性物质上。 纯活性化合物， 显著的最低抑菌浓度（MIC）将是 在已建立的动物模型中评价了体内功效， 播散性真菌病和分枝杆菌病，以确定 潜在的临床应用。

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.