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Biotechnol Adv. 2015 Dec;33(8):1582-1614. doi: 10.1016/j.biotechadv.2015.08.001. Epub 2015 Aug 15.

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

Author information

1
Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
2
Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
3
Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitätsplatz 4/I, 8010 Graz, Austria.
4
Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163-OC, 1060 Vienna, Austria.
5
Institute of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria.
6
Institute of Pharmacy/Pharmaceutical Chemistry and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
7
Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Humboldtstrasse 46/III, 8010 Graz, Austria.
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Contributed equally

Abstract

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.

KEYWORDS:

Computer modeling; Drug discovery; Ethnopharmacology; Medicine; Natural products; Organic synthesis; Pharmacology; Phytochemistry; Plant biotechnology; Plants

PMID:
26281720
PMCID:
PMC4748402
DOI:
10.1016/j.biotechadv.2015.08.001
[Indexed for MEDLINE]
Free PMC Article

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