NEW ANTIBIOTICS - ISOLATION, SYNTHESIS AND EVALUATION

这项研究的目标是研究目前存在于 高等植物提取物以发现新型抗生素 结构和新的作用模式，并确定其潜在的 用于治疗人类传染病。新型抗生素是 特别是为了治疗当代令人头疼的疾病 目前以发酵为基础的抗生素还不能完全 令人满意的原因是毒性，低效性，微生物抗性， 药代动力学特征差等。这一努力的核心 是对合适的植物材料的观察和植物学鉴定， 提取，针对使用的一组疾病指示生物进行筛选 在工业筛选程序中，生物测定定向分馏， 物理化学结构测定、合成(如图所示 结构澄清，制备大量的物质， 结构-活性关系的优化等)，In的评价 体外抗菌谱和效价与已建立的比较 感染实验动物的抗生素和体内评价。这个 后者通常由商业制药公司进行场外交易 具有从事这项工作的特殊设施和专业知识。在某些情况下 采用定向生物合成方法学来制备 特别是想要的目标分子。 目前主要屏幕的重点是针对以下对象的活动 革兰氏阳性和革兰氏阴性细菌、结核病、酵母和真菌 假单胞菌。在次级筛选中，性病生物，厌氧菌， 对军团菌和其他病原体进行检查。

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.