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Phytochemistry Reviews

, Volume 14, Issue 2, pp 299–315 | Cite as

The pharmaceutical industry and natural products: historical status and new trends

  • Bruno David
  • Jean-Luc WolfenderEmail author
  • Daniel A. Dias
Article

Abstract

Owing to the high diversity of terrestrial and marine organisms, natural products (secondary metabolites) are some of the most successful source of drug leads for the treatment of many diseases and illnesses. In the 1990s, advancements in automation [high-throughput screening (HTS)] and isolation technologies resulted in the surge in research towards natural products both in the fields of human health and agriculture. These strategies and techniques generated a substantial shift towards this ‘green Eldorado’, a real ‘Green Rush’ between 1990 and 2000. However, in the early 2000s most of the big Pharmas terminated their HTS and bioprospecting endeavours but to date, the low productivity of combichem and rational drug design is silently positioning pharmacognosy back on the rails and natural product discovery is remerging as a reputable source of current drugs on the market. Meanwhile, the World Health Organization has come to the realisation of the importance of biodiversity which would be able to offer affordable, therapeutic solutions to the majority of the world population. The preservation of the world’s biodiversity and its access is a critical issue which could hamper a serene utilisation of natural products in the developing world with herbal-based phytopharmaceuticals representing a significant share of the total world pharmaceutical market. This review presents an industrial perspective discussing natural product drug discovery, lead research, botanicals, pro-drugs, synergy effects, drugs interactions with botanicals, traditional medicines, reverse pharmacognosy and presents the difficulties in accessing biodiversity.

Keywords

Drug discovery High-throughput screening (HTS) Biodiversity Pharmaceutical industry Access and benefit sharing 

Notes

Conflict of interest

The authors state no conflict of interest and have received no payment in preparation of this manuscript.

References

  1. Anonymous (1992) United Nations. Convention on biological diversity. http://www.cbd.int/doc/legal/cbd-en.pdf. Cited 20 May 2014
  2. Anonymous (1973) Art 53 c of the The European Patent Convention, http://www.epo.org/law-practice/legal-texts/html/epc/2010/e/ar53.html Cited 20 May 2014
  3. Anonymus (2011) The Nagoya protocol on access to genetic resources and the fair and equitable sharing of benefits arising from their utilization to the convention on biological diversity. http://www.cbd.int/abs/doc/protocol/nagoya-protocol-en.pdf. Cited 20 May 2014
  4. Attinger P (2008) La médecine mésopotamienne. Journal des Médecines Cunéiformes 11–12:1–96PubMedGoogle Scholar
  5. Baker DD (2007) The value of natural products to future pharmaceutical discovery. Nat Prod Rep 27:1225–1244CrossRefGoogle Scholar
  6. Bauer RA, Wurst JM, Tan DS (2010) Expanding the range of ‘druggable’ targets with natural product-based libraries: an academic perspective. Curr Opin Chem Biol 14:308–314CrossRefPubMedCentralPubMedGoogle Scholar
  7. Berenbaum MC (1989) What is Synergy? Pharmacol Rev 41:93–141PubMedGoogle Scholar
  8. Beutler JA (2009) Natural products as a foundation for drug discovery. Curr Protoc Toxicol Supplement 46:9.11.1–9.11.21Google Scholar
  9. Bhatnagar I, Se-Kwon K (2010) Marine antitumor drugs: status, shortfalls and strategies. Mar Drugs 8:2702–2720CrossRefPubMedCentralPubMedGoogle Scholar
  10. Blunt JW, Copp BR, Munro MHG et al (2011) Marine natural products. Nat Prod Rep 28:196–268CrossRefPubMedGoogle Scholar
  11. Bruneton J (2009) Pharmacognosie, phytochimie, plantes médicinales. Paris, Tec & Doc – LavoisierGoogle Scholar
  12. Bunnage ME (2011) Getting pharmaceutical R&D back on target. Nat Chem Biol 7:335–339CrossRefPubMedGoogle Scholar
  13. Buriani A, Garcia-Bermejo ML, Bosisio E et al (2012) Omic techniques in systems biology approaches to traditional Chinese medicine research: present and future. J Ethnopharmacol 140:535–544CrossRefPubMedGoogle Scholar
  14. Butler MS (2005) Natural products to drugs: natural products derived compounds in clinical trials. Nat Prod Rep 22:162–195CrossRefPubMedGoogle Scholar
  15. Challal S, Bohni N, Buenafe OE et al (2012) Zebrafish bioassay-guided microfractionation for the rapid in vivo identification of pharmacologically active natural products. Chimia 66:229–232CrossRefPubMedGoogle Scholar
  16. Chen S-L, Jiang J-G (2012) Application of gene differential expression technology in the mechanism studies of nature product-derived drugs. Expert Opin Biol Ther 12:823–839CrossRefPubMedGoogle Scholar
  17. Chen ST, Dou J, Temple R et al (2008) New therapies from old medicines. Nat Biotechnol 26:1077–1083CrossRefPubMedGoogle Scholar
  18. Chen CH, Dickman KG, Moriya M et al (2012) Aristolochic acid-associated urothelial cancer in Taiwan. Proc Natl Acad Sci USA 109:8241–8246CrossRefPubMedCentralPubMedGoogle Scholar
  19. Colegate SM, Molyneux RJ (2008) Bioactive natural products: Detection, isolation and structure determination. CRC Press, Boca RatonGoogle Scholar
  20. Cragg GM (2007) Natural products as sources of new drugs over the last 25 years. J Nat Prod 70:461–477CrossRefPubMedGoogle Scholar
  21. Cragg GM, Newman DJ (2013) Natural products: a continuing source of novel drug leads. Biochim Biophys Acta 1830:3670–3695CrossRefPubMedCentralPubMedGoogle Scholar
  22. Cragg GM, Newman DJ, Snader KM (1997) Natural products in drug discovery and development. J Nat Prod 60:52–60CrossRefPubMedGoogle Scholar
  23. Cuevas C, Francesch A (2009) Development of Yondelis (trabectedin, ET-743). A semisynthetic process solves the supply problem. Nat Prod Rep 26:322–337CrossRefPubMedGoogle Scholar
  24. Dančík V, Seiler KP, Young DW et al (2010) Distinct biological network properties between the targets of natural products and disease genes. J Am Chem Soc 132:9259–9261CrossRefPubMedCentralPubMedGoogle Scholar
  25. David B, Ausseil F (2014) David B, Ausseil F (2014) Chapter 44. In: Hostettmann J, Stuppner H, Marston A, Chen S (eds) Handbook of chemical and biological plant analytical methods, 1st edn. Wiley, New JerseyGoogle Scholar
  26. Dewick PM (2009) Medicinal natural products: A biosynthentic approach, 3rd edn. Wiley, Great BritainCrossRefGoogle Scholar
  27. Dias DA, Urban S, Roessner U (2012) A historical overview of natural products in drug discovery. Metabolites 2:303–336CrossRefPubMedCentralPubMedGoogle Scholar
  28. Dickson M, Gagnon JP (2004) Key factors in the rising cost of new drug discovery and development. Nat Rev Drug Discov 3:417–429CrossRefPubMedGoogle Scholar
  29. Eldridge GR, Vervoort HC, Lee CM et al (2002) High-Throughput Method for the Production and Analysis of Large Natural Product Libraries for Drug Discovery. Anal Chem 74:3963–3971CrossRefPubMedGoogle Scholar
  30. Erkens RHJ (2011) What every chemist should know about plant names. Nat Prod Rep 28:11–14CrossRefPubMedGoogle Scholar
  31. Farnsworth NR (1990) The role of ethnopharmacology in drug development. In: Chadwick DJ, Marsh J (eds) Bioactive compounds from plants. John Wiley and Sons, ChichesterGoogle Scholar
  32. Feher M, Schmidt JM (2003) Property distributions: differences between drugs, natural products, and molecules from combinatorial chemistry. J Chem Inf Comput Sci 43:218–227CrossRefPubMedGoogle Scholar
  33. Fitzgerald JB, Schoeberl B, Nielsen UB et al (2006) Systems biology and combination therapy in the quest for clinical efficacy. Nat Chem Biol 2:458–466CrossRefPubMedGoogle Scholar
  34. Frearson JA, Collie IT (2009) HTS and hit finding in academia–from chemical genomics to drug discovery. Drug Discov Today 14:1150–1158CrossRefPubMedCentralPubMedGoogle Scholar
  35. Genilloud O (2012) Current challenges in the discovery of novel antibacterials from microbial natural products. Recent Patents on Anti-Infective Drug Dis 7:189–204CrossRefGoogle Scholar
  36. Gertsch J (2011) Botanical drugs, synergy, and network pharmacology: forth and back to intelligent mixtures. Plant Med 77:1086–1098CrossRefGoogle Scholar
  37. Gilbert N (2010) Biodiversity law could stymie research. Nature 463:598CrossRefPubMedGoogle Scholar
  38. Gilbert N (2012) Chinese herbal medicine breaks into EU market. Nature News Blog, http://blogs.nature.com/news/2012/04/chinese-herbal-medicine-breaks-into-eu-market.html Cited 20 May 2014
  39. Hammerness P, Basch E, Ulbricht C et al (2003) St. John’s wort: a systematic review of adverse effects and drug interactions for the consultation psychiatrist. Psychosomatics 44:271–282CrossRefPubMedGoogle Scholar
  40. Harvey AL (2008) Natural products in drug discovery. Drug Discovery Today 13:894–901CrossRefPubMedGoogle Scholar
  41. Helmstädter A, Staiger C (2013) Traditional use of medicinal agents: a valid source of evidence. Drug Discovery Today 19:4–7CrossRefPubMedGoogle Scholar
  42. Hoffman F, Kishter SR (2013) Botanical new drug applications - The Final Frontier. Herbalgram 99:66–69Google Scholar
  43. Hong J (2011) Role of natural product diversity in chemical biology. Curr Opin Chem Biol 15:350–354CrossRefPubMedCentralPubMedGoogle Scholar
  44. Jiang GC, Lin YC, Zhou SN et al (2000) Acta Sci. Nat. Univ. Sunyatseni 39:68Google Scholar
  45. Jiang Y, David B, Tu PF et al (2010) Recent analytical approaches in quality control of traditional Chinese medicines- A review. Anal Chim Acta 657:9–18CrossRefPubMedGoogle Scholar
  46. Kingston DGI (2011) Modern natural products drug discovery and its relevance to biodiversity cConservation. J Nat Prod 74:496–511CrossRefPubMedCentralPubMedGoogle Scholar
  47. Kleinrock M (2012) IMS institute for healthcare informatics—The global use of medicines: Outlook through 2016. www.theimsinstitute.org. Cited 20 May 2014
  48. Koehn FE, Carter GT (2005) The evolving role of natural products in drug discovery. Nat Rev Drug Discov 4:206–220CrossRefPubMedGoogle Scholar
  49. Krohn K, Dai JQ, Floerke U et al (2005) Botryane metabolites from the fungus Geniculosporium sp. isolated from the marine red alga Polysiphonia. J Nat Prod 68:400–405CrossRefPubMedGoogle Scholar
  50. Kusari S, Hertweck C, Spiteller M (2012) Chemical ecology of endophytic fungi: origins of secondary metabolites. Chem Biol 19:792–798CrossRefPubMedGoogle Scholar
  51. Lamottke K, Ripoll C, Walczak R (2011) The roots of innovation. European Biopharmaceutical Review 15:52–56Google Scholar
  52. Lauro G, Masullo M, Piacente S et al (2012) Inverse virtual screening allows the discovery of the biological activity of natural compounds. Bioorg & Med Chem 20:3596–3602CrossRefGoogle Scholar
  53. Lawson K (2013) Botanical and plant-derived drugs: Global markets. BCC Research, WellesleyGoogle Scholar
  54. Li YG, Huang WJ, Huang SY et al (2012) Screening of anti-cancer agent using zebrafish: comparison with the MTT assay. Biochem Biophys Res Comm 422:85–90CrossRefPubMedGoogle Scholar
  55. Macarrón R, Banks MN, Bojanic D et al (2011) Impact of high-throughput screening in biomedical research. Nat Rev Drug Discov 10:188–195CrossRefPubMedGoogle Scholar
  56. Mackay M (1998) Prescribed drugs: a major cause of ill health. Aust Health Rev 21:260–266CrossRefPubMedGoogle Scholar
  57. Matias EFF, Alves EF, Santos BS et al (2013) Biological activities and chemical characterization of Cordia verbenacea DC. as tool to validate the ethnobiological usage. Evid Based Complement Alternat Med 2013:164215CrossRefPubMedCentralPubMedGoogle Scholar
  58. Mayer AM, Glaser KB, Cuevas C et al (2010) The odyssey of marine pharmaceuticals: a current pipeline perspective. Trends Pharmacol Sci 31:255–265CrossRefPubMedGoogle Scholar
  59. McChesney JD, Venkataraman SK, Henri JT (2007) Plant natural products: back to the future or into extinction? Phytochemistry 68:2015–2022CrossRefPubMedGoogle Scholar
  60. McWilliams A (2006) Plant-derived drugs: Products, technology, applications (BIO022D) BBC Research, http://www.bbcresearch.com Cited 20 May 2014
  61. Michael S, Auld D, Klumpp C et al (2008) A robotic platform for quantitative high-throughput screening. Assay Drug Dev Technol 6:637–657CrossRefPubMedCentralPubMedGoogle Scholar
  62. Miller JS (2011) The discovery of medicines from plants: a current biological perspective. Econ Bot 65:396–407CrossRefGoogle Scholar
  63. Mishra BB, Tiwari VK (2011) Natural products: an evolving role in future drug discovery. Euro J Med Chem 46:4769–4807CrossRefGoogle Scholar
  64. Muller WE, Singer A, Wonnemann M (2001) Hyperforin - Antidepressant activity by a novel mechanism of action. Pharmacopsychiatry 34(suppl1):S98–S102CrossRefPubMedGoogle Scholar
  65. Naoghare PK, Song JM (2010) Chip-based high throughput screening of herbal medicines. Comb Chem High Throughout Screen 13:923–931CrossRefGoogle Scholar
  66. Newman DJ (2008) Natural products as leads to potential drugs: an old process or the new hope for drug discovery? J Med Chem 51:2589–2599CrossRefPubMedGoogle Scholar
  67. Newman DJ, Cragg GM (2007) Natural products as sources of new drugs over the last 25 years. J Nat Prod 70:461–477CrossRefPubMedGoogle Scholar
  68. Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75:311–335CrossRefPubMedCentralPubMedGoogle Scholar
  69. Newman DJ, Cragg GM, Snader KM (2003) Natural products as sources of new drugs over the period 1981-2002. J Nat Prod 66:1022–1037CrossRefPubMedGoogle Scholar
  70. Ngo LT, Okogun JI, Folk WR (2013) 21st century natural product research and drug development and traditional medicines. Nat Prod Rep 30:584–592CrossRefPubMedCentralPubMedGoogle Scholar
  71. Nicoletti M (2012) Nutraceuticals and botanicals: overview and perspectives. Int J Food Sci Nutr 63:2–6CrossRefPubMedGoogle Scholar
  72. Novodvorsky P, Da Costa MMJ, Chico TJA (2013) Zebrafish-based small molecule screens for novel cardiovascular drug. Drug Discov Today 10:e109–e114CrossRefGoogle Scholar
  73. Ortholand J-Y, Ganesan A (2004) Natural products and combinatorial chemistry: back to the future. Curr Opin Chem Biol 8:271–280CrossRefPubMedGoogle Scholar
  74. Paterson I, Anderson EA (2005) The renaissance of natural products as drug candidates. Science 310:451–453CrossRefPubMedGoogle Scholar
  75. Posadzki P, Watson L, Ernst E (2013) Herbdrug interactions: an overview of systematic reviews. Br J Clin Pharmacol 75:603–618PubMedCentralPubMedGoogle Scholar
  76. Ribnicky DM, Poulev A, Schmidt B et al (2008) Evaluation of botanicals for improving human health. Am J Clin Nutr 87:472S–475SPubMedGoogle Scholar
  77. Roessner U (2011) Metabolomics – The combination of analytical chemistry, biology and informatics. In: Moo-Young M (ed) Comprehensive Biotechnology, 2nd edn. Springer, Heidelberg, GermanyGoogle Scholar
  78. Rollinger JM (2011) Combination of ethnopharmacological knowhow with modern in silico tools. Planta Med 77:1230CrossRefGoogle Scholar
  79. Rollinger JM, Langer T, Stuppner H (2006) Strategies for efficient lead structure discovery from natural products. Curr Med Chem 13:1491–1507CrossRefPubMedGoogle Scholar
  80. Saklani A, Kutty SK (2008) Plant-derived compounds in clinical trials. DDT 13:161–171Google Scholar
  81. Sativex (2013) http://www.sativex.co.uk/healthcare-professionals Cited 27 Oct 2013
  82. Scheinfeld N (2008) Sinecatechins. Drugs Fut 33:27–30CrossRefGoogle Scholar
  83. Schmidt B, Ribnicky DM, Poulev A et al (2008) A natural history of botanical therapeutics. Metabolism 57:S3–S9CrossRefPubMedCentralPubMedGoogle Scholar
  84. Schmitt EK, Moore CM, Krastel P et al (2011) Natural products as catalysts for innovation: a pharmaceutical industry perspective. Curr Opin Chem Biol 15:497–504CrossRefPubMedGoogle Scholar
  85. Sheridan C (2012) Recasting natural product research. Nat Biotechnol 30:385–387Google Scholar
  86. Sertürner F (1817) Über das Morphium, eine neue salzfähige Grundlage und die Mekonsäure, als Hauptbestandtheile des Opiums. Ann Phys 55:56–89CrossRefGoogle Scholar
  87. Stickel F, Patsenker E, Schuppan D (2005) Herbal hepatotoxicity. J Hepatol 43:901–910CrossRefPubMedGoogle Scholar
  88. Swinney DC, Anthony J (2011) How where new medicine discovered? Nat Rev Drug Discov 10:507–519CrossRefPubMedGoogle Scholar
  89. Thomas GL, Johannes CW (2011) Natural product-like synthetic libraries. Curr Opin Chem Biol 15:516–522CrossRefPubMedGoogle Scholar
  90. U.S. Food and Drug Administration (2013) News and Events, FDA News Release (2012) FDA approves first anti-diarrheal drug for HIV/AIDS patients. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333701.htm. Cited 20 May 2014
  91. van der Kooy F, Maltese F, Hae Choi Y et al (2009) Quality control of herbal material and phytopharmaceuticals with MS and NMR based metabolic fingerprinting. Planta Med 75:763–775CrossRefPubMedGoogle Scholar
  92. van Wietmarschen H, Yuan K, Lu C et al (2009) Systems Biology Guided by Chinese Medicine Reveals New Markers for Sub-Typing Rheumatoid Arthritis Patients. J Clin Rheumatol 15:330–337CrossRefPubMedGoogle Scholar
  93. Verpoorte R (2012) Good Practices: the basis for evidence-based medicines. J Ethnopharmacol 140:455–457CrossRefPubMedGoogle Scholar
  94. Verpoorte R, Choi YH, Kim HK (2005) Ethnopharmacology and systems biology: a perfect holistic match. J Ethnopharmacol 100:53–56CrossRefPubMedGoogle Scholar
  95. Verpoorte R, Crommelin D, Danhof M et al (2009) Commentary: “A systems view on the future of medicine: inspiration from Chinese medicine?”. J Ethnopharmacol 121:479–481CrossRefPubMedGoogle Scholar
  96. Wagner H (2005) Natural products chemistry and phytomedicine in the 21st century: new developments and challenges. Pure Appl Chem 77:1–6CrossRefGoogle Scholar
  97. Wagner H (2011) Synergy research: approaching a new generation of phytopharmaceuticals. Fitoterapia 82:34–37CrossRefPubMedGoogle Scholar
  98. Wagner H, Ulrich-Merzenich G (2009) Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine 16:97–110CrossRefPubMedGoogle Scholar
  99. Wang L, Chen C (2013) Emerging applications of metabolomics in studying chemopreventive phytochemicals. Aaps Journal 15:941–950CrossRefPubMedCentralPubMedGoogle Scholar
  100. Wang M, Lamers R, Korthout H et al (2005a) Metabolomics in the context of systems biology: bridging traditional Chinese medicine and molecular pharmacology. Phytother Res 19:173–182CrossRefPubMedGoogle Scholar
  101. Wang Y, Tang H, Nicholson JK et al (2005b) A metabonomic strategy for the detection of the metabolic effects of chamomile (Matricaria recutita L.) ingestion. J Agric Food Chem 53:191–196CrossRefPubMedGoogle Scholar
  102. Woelk H (2000) Comparison of St John’s wort and imipramine for treating depression: randomised controlled trial. BMJ 321:536–539CrossRefPubMedCentralPubMedGoogle Scholar
  103. Wolfender J-L, Eugster PJ, Bohni N et al (2011) Advanced methods for natural product drug discovery in the field of nutraceuticals. Chimia 65:400–406CrossRefPubMedGoogle Scholar
  104. Xie G, Li X, Li H et al (2013) Toward personalized nutrition: comprehensive phytoprofiling and metabotyping. J Proteome Res 12:1547–1559CrossRefPubMedGoogle Scholar
  105. Yang M, Poon J, Wang S et al (2013) Application of Genetic Algorithm for Discovery of Core Effective Formulae in TCM Clinical Data. Comp. Math. Methods in Medicine 2013:1–16Google Scholar
  106. Yuliana ND, Khatib A, Choi YH et al (2011) Metabolomics for bioactivity assessment of natural products. Phytother Res 25:157–169PubMedGoogle Scholar
  107. Zhang HW, Song YC, Tan RX (2006) Biology and chemistry of endophytes. Nat Prod Rep 23:753–771CrossRefPubMedGoogle Scholar
  108. Zhang B, Peng Y, Zhang Z et al (2010) GAP production of TCM herbs in China. Planta Med 76:1948–1955CrossRefPubMedGoogle Scholar
  109. Zheng BC (1988) The earliest monograph on pharmaceuticals in China. J Tradit Chin Med 8:75–76PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Bruno David
    • 1
  • Jean-Luc Wolfender
    • 2
    Email author
  • Daniel A. Dias
    • 3
  1. 1.Pôle Actifs Végétaux - Branche Sourcing R&D et BotaniqueInstitut de Recherche Pierre FABREToulouseCedex, France
  2. 2.Phytochemistry and Bioactive Natural Products, School of Pharmaceutical SciencesUniversity of Geneva and University of LausanneGenevaSwitzerland
  3. 3.Metabolomics Australia, School of BotanyThe University of MelbourneParkvilleAustralia

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