NEW ANTIBIOTICS--ISOLATION, SYNTHESIS, AND EVALUATION

本研究的目的是研究存在于 高等植物提取物，以发现具有新的 结构和新的作用模式，并确定其潜力， 用于治疗人类感染性疾病。 新型抗生素是 特别是用来治疗当代棘手的疾病 目前的发酵抗生素还不能完全 由于毒性、低效力、微生物抗性， 药代动力学特性差等。 这一努力的核心是 是合适植物材料的获得和植物学鉴定， 提取、筛选一系列疾病指示生物， 在工业筛选程序中，生物测定定向分级， 物理化学结构测定、合成（如适用 结构澄清，大量制备， 结构-活性关系的优化等），评估的 体外抗菌谱和效力与已建立的 抗生素和在感染的实验动物中的体内评价。 的 后者通常由商业制药公司越位完成 拥有这项工作的特殊设施和专门知识。 在一些情况下 采用定向生物合成方法以制备 尤其是所需的靶分子。 目前，初级屏幕的重点是针对 革兰氏阳性菌和革兰氏阴性菌、结核菌、酵母菌和真菌， 假单胞菌 在第二次筛查中，性病微生物，厌氧菌， 检查军团菌和其他病原体。

The goal of this research is to study the antimicrobial agents present in higher plant extracts in order to discover antibiotics with novel structures and novel modes of action and to determine their potential for use in treatment of human infectious diseases. Novel antibiotics are especially sought for the treatment of contemporarily troublesome diseases against which current fermentation-based antibiotics are not fully satisfactory for reasons of toxicity, low potency, microbial resistance, poor pharmacokinetic characteristics, and the like. Central to this effort is the obtention and botanical identification of suitable plant material, extraction, screening against a battery of disease indicator organisms used in industrial screening programs, bioassay directed fractionation, physico-chemical structure determination, synthesis (where indicated for structural clarification, preparation of substantial quantities, optomization of structure-activity relationships, etc.), evaluation of in vitro antimicrobial spectrum and potency in comparison with established antibiotics and in vivo evaluation in infected experimental animals. The latter is usually done off-side by commercial pharmaceutical firms possessing special facilities and expertise for this work. In some cases directed biosynthetic methodology is employed in order to prepare especially desired target molecules. The present emphasis of the primary screen is activity against Gram-positive and Gram-negative bacteria, tuberculosis, yeast and fungi and pseudomonads. In secondary screens, venereal organisms, anaerobes, Legionella and other pathogens are examined.