TY - JOUR
T1 - Discovery and resupply of pharmacologically active plant-derived natural products
T2 - A review
AU - Atanasov, Atanas
AU - Waltenberger, Birgit
AU - Pferschy-Wenzig, Eva-Maria
AU - Linder, Tobias
AU - Wawrosch, Christoph
AU - Uhrin, Pavel
AU - Temml, Veronika
AU - Wang, Limei
AU - Schwaiger, Stefan
AU - Heiß, Elke
AU - Rollinger, Judith Maria
AU - Schuster, Daniela
AU - Breuss, Johannes M.
AU - Bochkov, Valery
AU - Mihovilovic, Marko
AU - Kopp, Brigitte
AU - Bauer, Rudolf
AU - Dirsch, Verena
AU - Stuppner, Hermann
N1 - Publisher Copyright:
© 2015 The Authors.
PY - 2015/8/15
Y1 - 2015/8/15
N2 - 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.
AB - 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.
KW - Computer modeling
KW - Drug discovery
KW - Ethnopharmacology
KW - Medicine
KW - Natural products
KW - Organic synthesis
KW - Pharmacology
KW - Phytochemistry
KW - Plant biotechnology
KW - Plants
UR - http://www.scopus.com/inward/record.url?scp=84940055507&partnerID=8YFLogxK
U2 - 10.1016/j.biotechadv.2015.08.001
DO - 10.1016/j.biotechadv.2015.08.001
M3 - Review
VL - 33
SP - 1582
EP - 1614
JO - Biotechnology Advances
JF - Biotechnology Advances
SN - 0734-9750
IS - 8
ER -