NEW ANTIBIOTICS--ISOLATION, SYNTHESIS, AND EVALUATION

这项拨款旨在资助来自高等植物的新次生代谢物。 具有新的化学结构并具有临床应用潜力的化合物 作为抗生素在治疗由微生物引起的感染方面的作用 目前哪些发酵衍生的抗生素在某些方面不令人满意 意义重大的方式。这项工作的核心是使用Rational现代测试 方法和在高等植物提取物中证实存在的结构 以及治疗上的新奇药物。一旦被证实是有效的，最有效的 植物提取物由生物测定技术指导进行分级，以便 以纯形式分离活性成分。然后对这些产品进行评估 比较它们的抗菌谱和体外比较效力 使用已有的抗生素。对感染的小鼠进行体内评价 最强大的特工出局了。新发现的特工经常出现在 少量，因此通常必须探索合成才能确认 结构，为重大评估和准备类似物做好足够的准备 探讨结构与活性的关系。后者是 有必要，因为抗生素中通常没有先例结构 文学指引着我们，因为我们渴望提高药用 其内在活性太弱而不能临床使用的物质的潜力 他们自己。这些方法攻击的疾病包括结核病， 由革兰氏阴性细菌引起的感染，性病，由 对已知抗生素和真菌疾病具有抗药性的生物体。

The grant is designed to cover new secondary metabolites from higher plants which have novel chemical structures and which have potential for clinical use as antibiotics in the treatment of infections caused by microorganisms against which current fermentation-derived antibiotics are unsatisfactory in some significant way. Central to this effort is the use of rational modern testing methods and the proven presence amongst higher plant extracts of structurally and therapeutically novel agents. Once confirmed to be active, the most potent plant extracts are fractionated guided by bioassay techniques in order to isolate the active constituents in pure form. These products are then evaluated for their antimicrobial spectrum and comparative potency in vitro in comparison with established antibiotics. In vivo evaluation in infected mice is carried out on the most potent agents. The new agents uncovered are often present in small amount so synthesis often has to be explored in order to confirm the structures, prepare enough for significant evaluation and to prepare analogues to explore the relationship between structure and activity. The latter is necessary because there are usually no precedent structures in the antibiotic literature to guide us and because of our desire to improve the medicinal potential of substances whose intrinsic activity is too weak for clinical use by themselves. The diseases under attack by these methods include tuberculosis, infections due to Gram-negative bacteria, venereal diseases, infections by organisms resistant to known antibiotics and fungal diseases.