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

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          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.

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          Most cited references449

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          Green chemistry: principles and practice.

          Green Chemistry is a relatively new emerging field that strives to work at the molecular level to achieve sustainability. The field has received widespread interest in the past decade due to its ability to harness chemical innovation to meet environmental and economic goals simultaneously. Green Chemistry has a framework of a cohesive set of Twelve Principles, which have been systematically surveyed in this critical review. This article covers the concepts of design and the scientific philosophy of Green Chemistry with a set of illustrative examples. Future trends in Green Chemistry are discussed with the challenge of using the Principles as a cohesive design system (93 references).
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            A TALE nuclease architecture for efficient genome editing.

            Nucleases that cleave unique genomic sequences in living cells can be used for targeted gene editing and mutagenesis. Here we develop a strategy for generating such reagents based on transcription activator-like effector (TALE) proteins from Xanthomonas. We identify TALE truncation variants that efficiently cleave DNA when linked to the catalytic domain of FokI and use these nucleases to generate discrete edits or small deletions within endogenous human NTF3 and CCR5 genes at efficiencies of up to 25%. We further show that designed TALEs can regulate endogenous mammalian genes. These studies demonstrate the effective application of designed TALE transcription factors and nucleases for the targeted regulation and modification of endogenous genes.
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              The atom economy--a search for synthetic efficiency.

              B. Trost (1991)
              Efficient synthetic methods required to assemble complex molecular arrays include reactions that are both selective (chemo-, regio-, diastereo-, and enantio-) and economical in atom count (maximum number of atoms of reactants appearing in the products). Methods that involve simply combining two or more building blocks with any other reactant needed only catalytically constitute the highest degree of atom economy. Transition metal-catalyzed methods that are both selective and economical for formation of cyclic structures, of great interest for biological purposes, represent an important starting point for this long-term goal. The limited availability of raw materials, combined with environmental concerns, require the highlighting of these goals.
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                Author and article information

                Journal
                8403708
                31674
                Biotechnol Adv
                Biotechnol. Adv.
                Biotechnology advances
                0734-9750
                1873-1899
                4 February 2016
                15 August 2015
                December 2015
                10 February 2016
                : 33
                : 8
                : 1582-1614
                Affiliations
                [a ]Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria
                [b ]Institute of Pharmacy/Pharmacognosy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria
                [c ]Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitätsplatz 4/I, 8010 Graz, Austria
                [d ]Institute of Applied Synthetic Chemistry, Vienna University of Technology, Getreidemarkt 9/163-OC, 1060 Vienna, Austria
                [e ]Institute of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, 1090 Vienna, Austria
                [f ]Institute of Pharmacy/Pharmaceutical Chemistry and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria
                [g ]Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Humboldtstrasse 46/III, 8010 Graz, Austria
                Author notes
                [* ]Corresponding authors. atanas.atanasov@ 123456univie.ac.at (A.G. Atanasov), birgit.waltenberger@ 123456uibk.ac.at (B. Waltenberger), eva-maria.wenzig@ 123456uni-graz.at (E.-M. Pferschy-Wenzig)
                Article
                EMS65118
                10.1016/j.biotechadv.2015.08.001
                4748402
                26281720
                a76e049f-b960-486d-bce1-85998046784e

                This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/).

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                Categories
                Article

                Biotechnology
                natural products,plants,drug discovery,phytochemistry,pharmacology,medicine,ethnopharmacology,computer modeling,organic synthesis,plant biotechnology

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