Discovery and resupply of pharmacologically active plant-derived natural products: A review

作者：Atanas G. Atanasov, Birgit Waltenberger, Eva‐Maria Pferschy‐Wenzig, Thomas Linder, Christoph Wawrosch, Pavel Uhrín, Veronika Temml, Limei Wang, Stefan Schwaiger, Elke H. Heiß, Judith M. Rollinger, Daniela Schuster, Johannes M. Breuss, Valery N. Bochkov, Marko D. Mihovilovič, Brigitte Kopp, Rudolf Bauer, Verena M. Dirsch, Hermann Stuppner · 发表于：Biotechnology Advances · 年份：2015 · DOI：10.1016/j.biotechadv.2015.08.001 · 被引用次数：2912 · 研究领域：Plant biochemistry and biosynthesis、Microbial Natural Products and Biosynthesis、Pharmacological Effects of Natural Compounds

Medicinal plants have historically proven their value as a source of molecules with therapeutic potential, and nowadays still represent an important pool for the identification of novel drug leads. In the past decades, pharmaceutical industry focused mainly on libraries of synthetic compounds as drug discovery source. They are comparably easy to produce and resupply, and demonstrate good compatibility with established high throughput screening (HTS) platforms. However, at the same time there has been a declining trend in the number of new drugs reaching the market, raising renewed scientific interest in drug discovery from natural sources, despite of its known challenges. In this survey, a brief outline of historical development is provided together with a comprehensive overview of used approaches and recent developments relevant to plant-derived natural product drug discovery. Associated challenges and major strengths of natural product-based drug discovery are critically discussed. A snapshot of the advanced plant-derived natural products that are currently in actively recruiting clinical trials is also presented. Importantly, the transition of a natural compound from a "screening hit" through a "drug lead" to a "marketed drug" is associated with increasingly challenging demands for compound amount, which often cannot be met by re-isolation from the respective plant sources. In this regard, existing alternatives for resupply are also discussed, including different biotechno...