What is it about?
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. Keywords: Natural products; Plants; Drug discovery; Phytochemistry; Pharmacology; Medicine; Ethnopharmacology; Computer modeling; Organic synthesis; Plant biotechnology, Abbreviations: 4CL, 4-coumaroyl CoA ligase; ADME/T, absorption, distribution, metabolism, excretion (and toxicity); BIA, benzylisoquinoline alkaloid; C4H, cinnamate 4-hydroxylase; CoA, coenzyme A; CRISPR/Cas9, clustered regulatory interspaced short palindromic repeat/CRISPR associated protein 9; DMPP, dimethylallyl-pyrophosphate; DNP, Dictionary of Natural Products; DNTI, Drugs from Nature Targeting Inflammation; EMA, European Medicines Agency; FDA, US Food and Drug Administration; GGPP, geranylgeranyl diphosphate; GPCR, G-protein coupled receptor; GC, gas chromatography; HPLC, high performance liquid chromatography; HTS, high-throughput screening; iNOS, inducible nitric oxide synthase; IPP, isopentenyl-pyrophosphate; MEP, 2C-methyl-d-erythriol-4-phosphate; MS, mass spectrometry; NCI, (US) National Cancer Institute; NCT, National Clinical Trial; NME, new molecular entity; NMR, nuclear magnetic resonance; NPD, Natural Product Database; OPLS-DA, orthogonal projection to latent structures discriminant analysis; PAL, phenylalanine ammonia lyase; PLS-DA, partial least square regression modeling discriminant analysis; PPAR, peroxisome proliferator-activated receptor; QSAR, quantitative structure activity relationship; TAL, tyrosine ammonia lyase; TALEN, transcription activator-like effector nuclease; TCM, traditional Chinese medicine; THC, tetrahydrocannabinol; SHE, safety, health, and environment
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Why is it important?
Natural products represent a very exciting research area, which can have a direct influence on human health, since natural products have the potential to be developed into very successful pharmaceutical drugs. For example, morphine, quinine, and many other essential medications are molecules derived from Nature.
Perspectives
Recognizing the potential of the natural molecules, the Austrian science fund (FWF) has recently financed a collaborative Austrian scientific network project called Drugs from Nature Targeting Inflammation (DNTI). The DNTI project gathered together scientists having expertise in almost all aspects relevant for natural molecules drug discovery, including phytochemistry, in vitro and in vivo pharmacology, biotechnology, ethnopharmacology, organic synthesis, and computer modeling. The combined multi-disciplinary expertise enabled DNTI participants to write together a joint very comprehensive review, summarizing the gathered experience, and broadly covering the natural molecules-based drug discovery research topic in a unique way. This work, entitled “Discovery and resupply of pharmacologically active plant-derived natural products: A review.” was very recently accepted for publication in Biotechnology Advances, an influential top-class scientific journal. The analysis that we have performed in this work yields many deep insides in this research sphere, and interestingly indicated recent sharply increasing interest in the area of natural compounds drug discovery research, in spite of the late lack-of-interest displayed by the pharma industry. Whereby this review provided an early indication for the reviving interest in natural compounds drug discovery research, a very strong signal pointing in the same direction was very soon afterwards provided also by the 2015 Nobel Prize in Physiology or Medicine, which went to William Campbell and Satoshi Omura, and Youyou Tu for their works related to the successful development of the pharmaceutical drugs Avermectin and Artemisinin, both of which represent molecules derived from the Nature.
Dr Atanas G. Atanasov
IGAB PAS
Read the Original
This page is a summary of: Discovery and resupply of pharmacologically active plant-derived natural products: A review, Biotechnology Advances, December 2015, Elsevier,
DOI: 10.1016/j.biotechadv.2015.08.001.
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