Wolfender Jean-Luc, Queiroz Emerson Ferreira
Phytochimie et Produits Naturels Bioactifs Ecole de Pharmacie Genève-Lausanne Section des Sciences Pharmaceutiques Université de Genève Quai Ansermet 30, CH-1211 Genève 4, Switzerland.
Chimia (Aarau). 2012;66(5):324-9. doi: 10.2533/chimia.2012.324.
Natural products (NPs) have historically been an important source of lead molecules in drug discovery. However, the interest that the pharmaceutical industry has had in NPs has declined in part because of the lack of compatibility of traditional natural-product extract libraries with high-throughput screenings and the low hit rate. Furthermore, in contrast to the synthetic libraries, compounds from natural sources are likely to have complex structures which slow down the identification process and contribute to problems related to supply and manufacturing. In this paper, we summarise some of the strategies that are being developed in our research unit to address these issues. On one hand, differential screening strategies were established with the aim of identifying dynamically induced NPs from silent biosynthetic pathways in plants and fungi that had been exposed to different stress situations. On the other hand, high-resolution HPLC techniques were optimised for biological and chemical profiling of crude extracts. This led to an integrated platform for rapid and efficient identification of new drug-leads and biomarkers of interest that were based on miniaturised technological approaches and metabolomics.
天然产物在药物发现中一直是先导分子的重要来源。然而，制药行业对天然产物的兴趣有所下降，部分原因是传统天然产物提取物文库与高通量筛选不兼容，且命中率较低。此外，与合成文库相比，天然来源的化合物结构可能较为复杂，这减缓了鉴定过程，并导致供应和生产方面的问题。在本文中，我们总结了我们研究单位正在开发的一些解决这些问题的策略。一方面，建立了差异筛选策略，旨在从暴露于不同应激情况的植物和真菌的沉默生物合成途径中鉴定动态诱导的天然产物。另一方面，优化了高分辨率HPLC技术，用于粗提物的生物学和化学分析。这形成了一个基于小型化技术方法和代谢组学的快速高效鉴定新型药物先导物和感兴趣生物标志物的综合平台。
