Discovery and resupply of pharmacologically active plant-derived natural products: A review.
Discovery and resupply of pharmacologically active plant-derived natural products: A review.
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DOI：
10.1016/j.biotechadv.2015.08.001
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发表时间：
2015-12
影响因子：
16
通讯作者：
Stuppner H
中科院分区：
文献类型：
--
作者：
Atanasov AG;Waltenberger B;Pferschy-Wenzig EM;Linder T;Wawrosch C;Uhrin P;Temml V;Wang L;Schwaiger S;Heiss EH;Rollinger JM;Schuster D;Breuss JM;Bochkov V;Mihovilovic MD;Kopp B;Bauer R;Dirsch VM;Stuppner H
药用植物在历史上已经证明了它们作为具有治疗潜力的分子来源的价值，并且现在仍然是鉴定新药先导物的重要来源。在过去的几十年里，制药业主要集中在合成化合物库作为药物发现的来源。它们易于生产和再供应，并与已建立的高通量筛选（HTS）平台具有良好的兼容性。然而，与此同时，进入市场的新药数量呈下降趋势，这引起了科学界对从自然来源发现药物的新兴趣，尽管这是一个已知的挑战。在这项调查中，历史发展的简要概述提供了与植物源天然产物药物发现相关的方法和最新发展的全面概述。相关的挑战和天然产物为基础的药物发现的主要优势进行了严格的讨论。还介绍了目前正在积极招募临床试验的先进植物源性天然产品的快照。重要的是，天然化合物从“筛选命中”通过“药物先导”到“上市药物”的转变与对化合物量的日益具有挑战性的需求相关，这通常不能通过从相应的植物来源重新分离来满足。在这方面，还讨论了现有的替代品，包括不同的生物技术方法和全有机合成。虽然天然产物为基础的药物发现的内在复杂性，需要高度集成的跨学科方法，审查的科学发展，最近的技术进步和研究趋势清楚地表明，天然产物将在未来的新药最重要的来源之一。
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 biotechnology approaches and total organic synthesis. While the intrinsic complexity of natural product-based drug discovery necessitates highly integrated interdisciplinary approaches, the reviewed scientific developments, recent technological advances, and research trends clearly indicate that natural products will be among the most important sources of new drugs also in the future.