University of North Carolina Greensboro, USA.
Nat Prod Rep. 2023 Jul 19;40(7):1153-1157. doi: 10.1039/d3np00017f.
Many researchers in the natural product sciences dream of discovering a successful drug. For almost all of us, this dream will never be realized. Among the heroes of our past, though, there is a team whose efforts led to the discovery of not one but two new drugs. Dr Monroe Wall and Dr Mansukh Wani isolated and solved the structures for taxol and camptothecin, plant-based compounds that continue to play a critical role in cancer therapy today. Since the 1960s and 1970s when Wall, Wani and collaborators did their seminal work, there have been tremendous technological advances in the natural product sciences. With access to most sophisticated technology, it might be expected that the rate of discovery of new drugs from plants and other sources would have sped up. However, this has not come to pass. Why is this? Is it that the promise of new drug candidates from plant-based sources has been exhausted? Has our fascination with new technologies and with the promise of the genomics revolution caused us to stop investing effort and resources in the practices that are proven to yield success? With this Viewpoint, we share the story of taxol's discovery, highlighting critical challenges that were overcome and considering their relevance to botanical natural products drug discovery today. We hope that consideration of lessons learned from the past will help fuel success by researchers currently studying plants with the goal of discovering promising therapeutic leads.
许多天然产物科学领域的研究人员都梦想发现一种成功的药物。对于我们大多数人来说,这个梦想永远不会实现。然而,在过去的英雄人物中,有一个团队的努力导致发现了不止一种而是两种新药。门罗·沃尔(Monroe Wall)博士和曼苏克·瓦尼(Mansukh Wani)博士分离并解决了紫杉醇和喜树碱的结构问题,这两种植物化合物至今仍在癌症治疗中发挥着关键作用。自 20 世纪 60 年代和 70 年代沃尔、瓦尼和合作者开展开创性工作以来,天然产物科学领域取得了巨大的技术进步。有了最先进的技术,人们可能会期望从植物和其他来源发现新药的速度会加快。然而,事实并非如此。为什么会这样呢?是否植物来源的新药候选物的前景已经耗尽?我们对新技术的迷恋以及对基因组革命的承诺是否导致我们停止投入精力和资源来实践那些已被证明能取得成功的方法?在这篇观点文章中,我们分享了紫杉醇发现的故事,强调了克服的关键挑战,并考虑了它们与当今植物学天然产物药物发现的相关性。我们希望,从过去的经验中吸取教训,将有助于激发目前正在研究植物以发现有前途的治疗线索的研究人员的成功。