Arthropod-Based Libraries for High Throughput Screening

描述(申请人提供)：在过去的40年里，我们一直在研究陆地昆虫和其他节肢动物之间的防御和交流的化学，这是一组包括地球上所有已描述物种的一半以上的有机体。虽然我们所表征的许多化合物具有简单的结构(如直链烯烃、羧酸、醛、酚、苯二酚)，但也有许多具有生物活性的生物碱、异戊二烯类(包括甾体)和具有新结构的多肽。我们计划选择大约10个最有趣的结构，并准备中试规模的文库，包括天然产物本身加上适合高通量筛选的数量-5-30个相关结构。从药物发现的角度来看，这个项目是我们多年来在天然产物化学领域研究的成果。DS和建议的衍生物通常代表尚未通过高通量筛选检验的分子结构。在这些文库中发现与神经药理学、传染病和寄生虫病或癌症等领域相关的活动的可能性，远远高于对化学空间其他领域的研究，这些领域不是基于生物起源的小分子。

DESCRIPTION (provided by applicant): Over the past four decades, we have been studying the chemistry of defense and communication among terrestrial insects and other arthropods, a group of organisms that includes over half of all described species on earth. While many of the compounds we have characterized have simple structures (such as straight chain alkenes, carboxylic acids, aldehydes, phenols, benzoquinones), there are also many examples of biologically active alkaloids, isoprenoids (including steroids), and polypeptides with novel structures which we have discovered in the course of this research. We plan to select approximately ten of the most interesting structures and to prepare pilot-scale libraries consisting of the natural product itself plus -5-30 related structures in quantities suitable for high throughput screening. This project is the culmination, from the viewpoint of drug discovery, of our many years of research in the field of natural products chemistry. ds and proposed derivatives generally represent molecular structures that have not yet been examined via high throughput screening. The likelihood of discovering activities within these libraries of relevance to areas such as neuron-pharmacology, infectious and parasitic diseases, or cancer is much greater than would be expected from a study of other areas of chemical space which are not based on small molecules of biological origin.