Department of Chemistry, Institute for Genomic Biology, Cancer Center at Illinois, University of Illinois, Urbana-Champaign, USA.
Nat Prod Rep. 2020 Nov 18;37(11):1395-1403. doi: 10.1039/d0np00059k.
Covering: up to 2020 Natural products have a long history in drug discovery, with their inherent biological activity often tailored by medicinal chemists to arrive at the final drug product. This process is illustrated by numerous examples, including the conversion of epothilone to ixabepilone, erythromycin to azithromycin, and lovastatin to simvastatin. However, natural products are also fruitful starting points for the creation of complex and diverse compounds, especially those that are markedly different from the parent natural product and accordingly do not retain the biological activity of the parent. The resulting products have physiochemical properties that differ considerably when compared to traditional screening collections, thus affording an opportunity to discover novel biological activity. The synthesis of new structural frameworks from natural products thus yields value-added compounds, as demonstrated in the last several years with multiple biological discoveries emerging from these collections. This Highlight details a handful of these studies, describing new compounds derived from natural products that have biological activity and cellular targets different from those evoked/engaged by the parent. Such re-engineering of natural products offers the potential for discovering compounds with interesting and unexpected biological activity.
截至 2020 年，天然产物在药物发现方面有着悠久的历史，其内在的生物活性经常被药物化学家修饰，以达到最终的药物产品。这一过程有许多例子，包括埃坡霉素转化为伊沙匹隆、红霉素转化为阿奇霉素以及洛伐他汀转化为辛伐他汀。然而，天然产物也是创造复杂多样化合物的富有成效的起点，特别是那些与母体天然产物明显不同的化合物，因此不保留母体的生物活性。由此产生的产物与传统的筛选库相比，具有明显不同的理化性质，从而为发现新的生物活性提供了机会。因此，从天然产物中合成新的结构框架产生了附加值化合物，这在过去几年中已经通过这些化合物库的多个生物发现得到了证明。本文重点介绍了其中的一些研究，描述了从天然产物衍生而来的具有不同于母体的生物活性和细胞靶标的新化合物。对天然产物进行这种重新设计有可能发现具有有趣和意外生物活性的化合物。
