Advertisement

How to Succeed in Marketing Marine Natural Products for Nutraceutical, Pharmaceutical and Cosmeceutical Markets

  • Ricardo Calado
  • Miguel Costa Leal
  • Helena Gaspar
  • Susana Santos
  • António Marques
  • Maria Leonor Nunes
  • Helena Vieira
Chapter
Part of the Grand Challenges in Biology and Biotechnology book series (GCBB)

Abstract

The marine ecosystem shelters a vast number of macro- and microorganisms that have developed unique metabolic skills to survive in diverse and hostile habitats. These survival strategies often result in the biosynthesis of an array of secondary metabolites with specific activities and functions in the cellular context. Several metabolites can give origin to high-value commercial products for nutraceutical, pharmaceutical and cosmeceutical markets, among others. This chapter outlines those industries’ paths for marketing marine natural products (MNPs), from discovery and development up to final product marketing. Focus is given on compounds that successfully reached the market and, particularly, the approaches employed by the nutraceutical, pharmaceutical and cosmeceutical companies that succeeded in marketing those products. Some key failures in each market segment are analysed, allowing lessons to be learned and key hurdles to be avoided in MNP development. The main challenges faced during MNP programs are assessed and mapped in the market funnel of common product development routes. Suggestions to surpass these challenges are provided, in order to improve market entry success rates of highly promising marine bioactives in current pipelines, highlighting what can be applied to novel and/or ongoing MNP development programs.

Notes

Acknowledgements

This work was financed by national funds through the Portuguese Foundation for Science and Technology (Fundação para a Ciência e Tecnologia) within the scope of projects UID/Multi/04046/2013 (BioISI, Biosystems and Integrative Sciences Institute) UID/Multi/00612/2013 (CQB, Chemistry and Biochemistry Centre) and UID/MAR/04292/2013 (MARE—Marine and Environmental Sciences Centre). Thanks are also due to FCT/MEC through national funds and the co-funding by the FEDER, within the PT2020 Partnership Agreement and Compete 2020 for the financial support to CESAM (UID/AMB/50017/2013).

References

  1. 1.
    Costello MJ, May RM, Stork NE (2013) Can we name Earth’s species before they go extinct? Science 339:413–416PubMedCrossRefGoogle Scholar
  2. 2.
    McGinn AP (1999) Safeguarding the health of oceans, vol 145. Worldwatch Institute, DanversGoogle Scholar
  3. 3.
    Devries DJ, Hall MR (1994) Marine biodiversity as a source of chemical diversity. Drug Dev Res 33(2):161–173CrossRefGoogle Scholar
  4. 4.
    Leal MC, Puga J, Serôdio J, Gomes NCM, Calado R (2012) Trends in the discovery of new marine natural products from invertebrates over the last two decades – where and what are we bioprospecting? PLoS One 7(1):e30580.  https://doi.org/10.1371/journal.pone.0030580.t003 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Leal MC, Munro MHG, Blunt JW et al (2013) Biogeography and biodiscovery hotspots of macroalgal marine natural products. Nat Prod Rep 30:1380–1390PubMedCrossRefGoogle Scholar
  6. 6.
    Montaser R, Luesch H (2011) Marine natural products: a new wave of drugs? Future Med Chem 3(12):1475–1489.  https://doi.org/10.4155/fmc.11.118 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Martins A, Vieira H, Gaspar H, Santos S (2014) Marketed marine natural products in the pharmaceutical and cosmeceutical industries: tips for success. Mar Drugs 12:1066–1101PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75(3):311–335.  https://doi.org/10.1021/np200906s CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Imhoff JF, Labes A, Wiese J (2011) Bio-mining the microbial treasures of the ocean: new natural products. Biotechnol Adv 29(5):468–482.  https://doi.org/10.1016/j.biotechadv.2011.03.001 CrossRefPubMedGoogle Scholar
  10. 10.
    National Research Council (2002) Marine biotechnology in the twenty-first century: problems, promise and products. National Academies Press, Washington, DCGoogle Scholar
  11. 11.
    Munro M, Blunt JW, Dumdei E et al (1999) The discovery and development of marine compounds with pharmaceutical potential. J Biotechnol 70:15–25PubMedCrossRefGoogle Scholar
  12. 12.
    Leal MC, Madeira C, Brandao CA, Puga J, Calado R (2012) Bioprospecting of marine invertebrates for new natural products – a chemical and zoogeographical perspective. Molecules 17(8):9842–9854.  https://doi.org/10.3390/molecules17089842 CrossRefPubMedGoogle Scholar
  13. 13.
    Leal MC, Hilário A, Munro HG, Blunt JW, Calado R (2016) Natural products discovery needs improved taxonomic and geographic information. Nat Prod Rep 33:747–750PubMedCrossRefGoogle Scholar
  14. 14.
    Lederer E, Teissier G, Huttrer C (1940) The isolation and chemical composition of calliactine, pigment of the sea anemone “Sargatia parasitica” (Calliactis effoeta). Bull Soc Chim Fr 7:608–615Google Scholar
  15. 15.
    MarinLit: A database of the marine natural products literature (2016)Google Scholar
  16. 16.
    Skropeta D (2008) Deep-sea natural products. Nat Prod Rep 25(6):1131–1166.  https://doi.org/10.1039/b808743a CrossRefPubMedGoogle Scholar
  17. 17.
    Kinghorn AD, Chin Y-W, Swanson SM (2009) Discovery of natural product anticancer agents from biodiverse organisms. Curr Opin Drug Discov Dev 12(2):189–196Google Scholar
  18. 18.
    WoRMS Editorial Board (2016) World register of marine species. http://www.marinespecies.org at VLIZ. Accessed 19 Dec 2016. doi:10.14284/170
  19. 19.
    Haefner B (2003) Drugs from the deep: marine natural products as drug candidates. Drug Discov Today 8(12):536–544.  https://doi.org/10.1016/S1359-6446(03)02713-2 CrossRefPubMedGoogle Scholar
  20. 20.
    Leal MC, Sheridan C, Osinga R et al (2014) Marine microorganism-invertebrate assemblages: perspectives to solve the “supply problem” in the initial steps of drug discovery. Mar Drugs 12:3929–3952PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Pettit GR, Fujii Y, Hasler JA, Schmidt JM (1982) Isolation and characterization of palystatins A–D. J Nat Prod 45:4Google Scholar
  22. 22.
    Kim S-K (ed) (2012) Marine cosmeceuticals: trends and prospects. CRC Press, Taylor & Francis Group, Boca Raton, FLGoogle Scholar
  23. 23.
    Hurst D, Børresen T, Almesjö L, De Raedemaecker F, Bergseth S (2016) Marine biotechnology strategic research and innovation roadmap: insights to the future direction of European marine biotechnology, 1st edn. Marine Biotechnology ERA-NET, OostendeGoogle Scholar
  24. 24.
    Gomez-Ordonez E, Jimenez-Escrig A, Ruperez P (2010) Dietary fibre and physico-chemical properties of several edible seaweeds from the North western Spanish coast. Food Res Int (9):2289–2294CrossRefGoogle Scholar
  25. 25.
    Plaza M, Cifuentes A, Ibanez E (2008) In the search of new functional food ingredients from algae. Trends Food Sci Technol 19(1):31–39.  https://doi.org/10.1016/j.tifs.2007.07.012 CrossRefGoogle Scholar
  26. 26.
    Jimenez-Escrig A, Sanchez-Muniz FJ (2000) Dietary fibre from edible seaweeds: chemical structure, physicochemical properties and effects on cholesterol metabolism. Nutr Res 20(4):585–598.  https://doi.org/10.1016/S0271-5317(00)00149-4 CrossRefGoogle Scholar
  27. 27.
    Ruperez P, Saura-Calixto F (2001) Dietary fibre and physicochemical properties of edible Spanish seaweeds. Eur Food Res Technol 212:349–354CrossRefGoogle Scholar
  28. 28.
    Hu GP, Yuan J, Sun L et al (2011) Statistical research on marine natural products based on data obtained between 1985 and 2008. Mar Drugs 9:514–525PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Shahidi F (2009) Nutraceuticals and functional foods: whole versus processed foods. Trends Food Sci Technol 20:376–387CrossRefGoogle Scholar
  30. 30.
    Shahidi F, Zhong Y (2005) Marine mammal oils. In: Bailey’s industrial oil and fat products, 6th edn. Wiley, New York, pp 259–278CrossRefGoogle Scholar
  31. 31.
    Foundation ES (2010) Marine biotechnology: a new vision and strategy for Europe Marine Board. ESF Position Paper n° 15:96Google Scholar
  32. 32.
    Afonso C, Costa S, Cardoso C et al (2015) Evaluation of the risk/benefit associated to the consumption of raw and cooked farmed meagre based on the bioaccessibility of selenium, eicosapentaenoic acid and docosahexaenoic acid, total mercury, and methylmercury determined by an in vitro digestion model. Food Chem 170:249–256.  https://doi.org/10.1016/j.foodchem.2014.08.044 CrossRefPubMedGoogle Scholar
  33. 33.
    Kaur G, Cameron-Smith D, Garg M, Sinclair AJ (2011) Docosapentaenoic acid (22:5n-3): a review of its biological effects. Prog Lipid Res 50(1):28–34.  https://doi.org/10.1016/j.plipres.2010.07.004 CrossRefPubMedGoogle Scholar
  34. 34.
    Bandarra NM, Batista I, Nunes ML (2011) In: Chen G (ed) Fatty acids: types, roles and health effects. Nova Science, Hauppauge, NY (ebook)Google Scholar
  35. 35.
    Byelashov OA, Sinclair AJ, Kaur G (2015) Dietary sources, current intakes, and nutritional role of omega-3 docosapentaenoic acid. Lipid Technol 27(4):79–82.  https://doi.org/10.1002/lite.201500013 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Lordan S, Ross RP, Stanton C (2011) Marine bioactives as functional food ingredients: potential to reduce the incidence of chronic diseases. Mar Drugs 9(6):1056–1100.  https://doi.org/10.3390/md9061056 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Ngo DH, Vo TS, Ngo DN, Wijesekara I, Kim SK (2012) Biological activities and potential health benefits of bioactive peptides derived from marine organisms. Int J Biol Macromol 51(4):378–383.  https://doi.org/10.1016/j.ijbiomac.2012.06.001 CrossRefPubMedGoogle Scholar
  38. 38.
    Shukla S (2016) Therapeutic importance of peptides from marine source: a mini review. Ind J Geo-Mar Sci 45:1422–1431Google Scholar
  39. 39.
    Suleria HA, Osborne S, Masci P, Gobe G (2015) Marine-based nutraceuticals: an innovative trend in the food and supplement industries. Mar Drugs 13(10):6336–6351.  https://doi.org/10.3390/md13106336 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Mozaffarian D, Rimm EB (2006) Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA 296(15):1885–1899.  https://doi.org/10.1001/jama.296.15.1885 CrossRefPubMedGoogle Scholar
  41. 41.
    Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J (2006) Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review. Atherosclerosis 189(1):19–30.  https://doi.org/10.1016/j.atherosclerosis.2006.02.012 CrossRefPubMedGoogle Scholar
  42. 42.
    Calder PC (2006) n-3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 83(6 Suppl):1505S–1519SPubMedCrossRefGoogle Scholar
  43. 43.
    Chapkin RS, Davidson LA, Ly L, Weeks BR, Lupton JR, McMurray DN (2007) Immunomodulatory effects of (n-3) fatty acids: putative link to inflammation and colon cancer. J Nutr 137(1 Suppl):200S–204SPubMedCrossRefGoogle Scholar
  44. 44.
    Sun H, Berquin IM, Edwards IJ (2005) Omega-3 polyunsaturated fatty acids regulate syndecan-1 expression in human breast cancer cells. Cancer Res 65(10):4442–4447.  https://doi.org/10.1158/0008-5472.CAN-04-4200 CrossRefPubMedGoogle Scholar
  45. 45.
    Brasky TM, Darke AK, Song X et al (2013) Plasma phospholipid fatty acids and prostate cancer risk in the SELECT trial. J Natl Cancer Inst 105(15):1132–1141.  https://doi.org/10.1093/jnci/djt174 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Uauy R, Dangour AD (2006) Nutrition in brain development and aging: role of essential fatty acids. Nutr Rev 64(5 Pt 2):S24–S33; discussion S72–S91CrossRefGoogle Scholar
  47. 47.
    Peet M, Stokes C (2005) Omega-3 fatty acids in the treatment of psychiatric disorders. Drugs 65(8):1051–1059PubMedCrossRefGoogle Scholar
  48. 48.
    EFSA Panel on Dietetic Products NaAN (2012) Scientific opinion related to the tolerable upper intake level of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA). EFSA J 10(7):48Google Scholar
  49. 49.
    Barrow CJ, Nolan C, MacLead M, Santosa S, Holub BJ (2009) Bioequivalence of encapsulated and microencapsulated fish-oil supplementation. J Funct Foods 1:38–43CrossRefGoogle Scholar
  50. 50.
    Chen Q, McGillivray D, Wen J, Zhong F, Quek S (2013) Co-encapsulation of fish oil with phytosterol esters and limonene by milk proteins. J Food Eng 117:505–512CrossRefGoogle Scholar
  51. 51.
    Chatterjee S, Judeh ZMA (2016) Microencapsulation of fish oil. Lipid Technol 28:13–15CrossRefGoogle Scholar
  52. 52.
    Wanasundara UN, Wanasundara J, Shahidi F (2002) Omega-3 fatty acid concentrates: a review of production technologies. In: Alasalvarand C, Taylor T (eds) Seafoods: quality, technology and nutraceutical applications. Springer, New York, pp 157–174CrossRefGoogle Scholar
  53. 53.
    (BIOHAZ) EPoCH (2010) Scientific opinion on fish oil for human consumption. Food hygiene, including rancidity. EFSA J 8(10):1874CrossRefGoogle Scholar
  54. 54.
    Beer C (2011) Krill: the ocean’s gold. Nutraceuticals World. http://www.nutraceuticalsworld.com/contents/view_features/2011-10-03/krill-the-oceans-gold
  55. 55.
  56. 56.
    Moloughney S (2011) Diving deep into the marine nutraceuticals market – consumers continue to ride the ocean’s waves to better health. Nutraceuticals World. October, p 44–52. http://www.nutraceuticalsworld.com/contents/view_features/2011-10-03/diving-deep-into-the-marine-nutraceuticals-market
  57. 57.
    Lee CM, Barrow CJ, Kim S, Miyashita K, Shahidi F (2012) Global trends in marine nutraceuticals. Food Technol 65:23–31Google Scholar
  58. 58.
    Shahidi F (2003) Nutraceuticals and bioactives from seafood byproducts. In: Bechtel PJ (ed) Advances in seafood byproducts: 2002 Conference proceedings Alaska Sea Grant College Program. University of Alaska Fairbanks, Fairbanks, p 566Google Scholar
  59. 59.
    Kim SK, Mendis E (2006) Bioactive compounds from marine processing byproducts – a review. Food Res Int 39:383–393CrossRefGoogle Scholar
  60. 60.
    Kim SK, Wijesekara I (2010) Development and biological activities of marine-derived bioactive peptides: a review. J Funct Foods 2:1–9CrossRefGoogle Scholar
  61. 61.
    FAO (2016) The state of world fisheries and aquaculture 2016. Contributing to food security and nutrition for all, RomeGoogle Scholar
  62. 62.
    Nunes ML, Bandarra NM, Batista I (2011) Health benefits associated with seafood consumption. In: Alasalvar C, Shahidi F, Miyashita K, Wanasundara U (eds) Handbook of seafood quality, safety and health applications, vol 122. Blackwell, Oxford, pp 876–883Google Scholar
  63. 63.
    Bernstein AM, Sun Q, Hu FB, Stampfer MJ, Manson JE, Willett WC (2010) Major dietary protein sources and risk of coronary heart disease in women. Circulation 122(9):876–883.  https://doi.org/10.1161/CIRCULATIONAHA.109.915165 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Tremblay F, Lavigne C, Jacques H, Marette A (2003) Dietary cod protein restores insulin-induced activation of phosphatidylinositol 3-kinase/Akt and GLUT4 translocation to the T-tubules in skeletal muscle of high-fat-fed obese rats. Diabetes 52(1):29–37PubMedCrossRefGoogle Scholar
  65. 65.
    Paddon-Jones D, Westman E, Mattes RD, Wolfe RR, Astrup A, Westerterp-Plantenga M (2008) Protein, weight management, and satiety. Am J Clin Nutr 87(5):1558S–1561SPubMedCrossRefGoogle Scholar
  66. 66.
    Hultin HO, Kristinsson HG, Lanier TC, Park JW (2005) Process for recovery of functional proteins by pH shifts. In: Park JW (ed) Surimi and surimi seafood. CRC Press, Boca Raton, FL, pp 107–139CrossRefGoogle Scholar
  67. 67.
    Gehring CK, Gigliotti JC, Moritz JS, Tou JC, Jaczynski J (2011) Functional and nutritional characteristics of proteins and lipids recovered by isoelectric processing of fish by-products and low-value fish: a review. Food Chem 124:422–431CrossRefGoogle Scholar
  68. 68.
    Hultin HO, Kelleher SD (1999) Process for isolating a protein composition from a muscle source and protein composition. US Patent 6,005,073Google Scholar
  69. 69.
    Hultin HO, Kelleher SD (2000) High efficiency alkaline protein extraction. US Patent 6,136,959Google Scholar
  70. 70.
    Jamilah B, Harvinder KG (2002) Properties of gelatins from skins of fish – black tilapia (Oreochromis mossambicus) and red tilapia (Oreochromis nilotica). J Food Chem 77:81–84CrossRefGoogle Scholar
  71. 71.
    Karim AA, Bhat R (2009) Fish gelatin: properties, challenges, and prospects as an alternative to mammalian gelatins. Food Hydrocoll 23:563–576CrossRefGoogle Scholar
  72. 72.
    Aspmo SI, Horn SJ, Eijsink VGH (2005) Enzymatic hydrolysis of Atlantic cod (Gadus morhua L.) viscera. Process Biochem 40:1957–1966CrossRefGoogle Scholar
  73. 73.
    Batista I, Pires C, Teixeira B, Nunes ML (2014) Hidrolisados proteicos com atividade biológica: uma alternativa para a valorização de subprodutos de pescado. Boletim de Biotecnologia 2ª Série(5):37–39Google Scholar
  74. 74.
    Guérard F, Dufossé L, De La Broise D, Binet A (2001) Enzymatic hydrolysis of proteins from yellowfin tuna (Thunnus albacares) wastes using alcalase. J Mol Catal B Enzym 11:1051–1059CrossRefGoogle Scholar
  75. 75.
    Kristinsson HG, Rasco BA (2000) Biochemical and functional properties of Atlantic salmon (Salmo salar) muscle proteins hydrolyzed with various alkaline proteases. J Agric Food Chem 48(3):657–666PubMedCrossRefGoogle Scholar
  76. 76.
    Pedersen B (1994) Removing of bitterness from protein hydrolysates. Food Technol 45(10):96–98Google Scholar
  77. 77.
    Nilsang S, Lertsiri S, Suphantharika M, Assavanig A (2005) Optimization of enzymatic hydrolysis of fish soluble concentrate by commercial proteases. J Food Eng 70:571–578CrossRefGoogle Scholar
  78. 78.
    Benjakul S, Yarnpakdee S, Senphan T, Halldorsdottir SM, Kristinsson HG (2014) Fish protein hydrolysates: production, bioactivities and applications. In: Kristinsson HG (ed) Antioxidants and functional components in aquatic foods, 1st edn. Matil Ltd, Reykjavik, Iceland, pp 237–283CrossRefGoogle Scholar
  79. 79.
    Guerard F, Decourcelle N, Sabourin C et al (2010) Recent developments of marine ingredients for food and nutraceutical applications: a review. J Sci Hal Aquat 2:21–27Google Scholar
  80. 80.
    Cardoso C, Nunes ML (2013) Improved utilization of fish waste, discards, and by-products and low-value fish towards food and health products. In: Galvez RP, Bergé J-P (eds) Utilization of fish waste. Taylor & Francis Group, Boca Raton, FL, pp 26–58CrossRefGoogle Scholar
  81. 81.
    Vermeirssen V, Van Camp J, Verstraete W (2004) Bioavailability of angiotensin I converting enzyme inhibitory peptides. Br J Nutr 92(3):357–366PubMedCrossRefGoogle Scholar
  82. 82.
    López-Fandiño R, Otte J, Van Camp J (2006) Physiological, chemical and technological aspects of milk-protein-derived peptides with antihypertensive and ACE-inhibitory activity. Int Dairy J 16:1277–1293CrossRefGoogle Scholar
  83. 83.
    Murray BA, FitzGerald RJ (2007) Angiotensin converting enzyme inhibitory peptides derived from food proteins: biochemistry, bioactivity and production. Curr Pharm Des 13(8):773–791PubMedCrossRefGoogle Scholar
  84. 84.
    López Expoósito I, Recio I (2006) Antibacterial activity of peptides and folding variants from milk proteins. Int Dairy J 16:1294–1305CrossRefGoogle Scholar
  85. 85.
    Mendis E, Rajapakse N, Byun HG, Kim SK (2005) Investigation of jumbo squid (Dosidicus gigas) skin gelatine peptides for their in vitro antioxidant effects. Life Sci 77:2166–2178PubMedCrossRefGoogle Scholar
  86. 86.
    Sarmadi BH, Ismail A (2010) Antioxidative peptides from food proteins: a review. Peptides 31(10):1949–1956.  https://doi.org/10.1016/j.peptides.2010.06.020 CrossRefPubMedGoogle Scholar
  87. 87.
    Erdmann K, Cheung BW, Schroder H (2008) The possible roles of food-derived bioactive peptides in reducing the risk of cardiovascular disease. J Nutr Biochem 19(10):643–654.  https://doi.org/10.1016/j.jnutbio.2007.11.010 CrossRefPubMedGoogle Scholar
  88. 88.
    Shahidi F, Janak Kamil YVA (2001) Enzymes from fish and aquatic invertebrates and their application in the food industry. Trends Food Sci Technol 12:435–464CrossRefGoogle Scholar
  89. 89.
    Bourseau PL, Vandanjon P, Jaouen M et al (2009) Fractionation of fish protein hydrolysates by ultrafiltration and nanofiltration: impact on peptidic populations. Desalination 244:303–320CrossRefGoogle Scholar
  90. 90.
    Picot L, Ravallec R, Fouchereau-Peron M et al (2010) Impact of ultrafiltration and nanofiltration of an industrial fish protein hydrolysate on its bioactive properties. J Sci Food Agric 90(11):1819–1826.  https://doi.org/10.1002/jsfa.4020 CrossRefPubMedGoogle Scholar
  91. 91.
    Dutta PK, Dutta J, Tripathi VS (2004) Chitin and chitosan: chemistry, properties and applications. J Scientif Indus Res 63:20–31Google Scholar
  92. 92.
    Kamil J, Jeon YJ, Shahidi F (2002) Antioxidant activity of chitosans of different viscosity in cooked comminuted flesh of herring (Clupea harengus). Food Chem 79:69–77CrossRefGoogle Scholar
  93. 93.
    Park PJ, Je JY, Kim SK (2003) Free radical scavenging activity of chitooligosaccharides by electron spin resonance spectrometry. J Agric Food Chem 51(16):4624–4627.  https://doi.org/10.1021/jf034039+ CrossRefPubMedGoogle Scholar
  94. 94.
    Rosa R, Nunes ML (2008) Crustáceos: Exploração, bioquímica, conservação e aproveitamento de sub-produtos. Publicações Avulsas do Instituto de Investigação das Pescas e do Mar, IPIMAR, Lisboa, PortugalGoogle Scholar
  95. 95.
    Chandy T, Sharma CP (1990) Chitosan–as a biomaterial. Biomater Artif Cells Artif Organs 18(1):1–24PubMedCrossRefGoogle Scholar
  96. 96.
    Kadam SU, Prabhasankar P (2010) Marine foods as functional ingredients in bakery and pasta products. Food Res Int 43:1975–1980CrossRefGoogle Scholar
  97. 97.
    Hayes M, Carney B, Slater J, Bruck W (2008) Mining marine shellfish wastes for bioactive molecules: chitin and chitosan–Part B: applications. Biotechnol J 3(7):878–889.  https://doi.org/10.1002/biot.200800027 CrossRefPubMedGoogle Scholar
  98. 98.
    Dawczynski C, Schubert R, Jahreis G (2007) Amino acids, fatty acids, and dietary fibre in edible seaweed products. Food Chem 103:891–899CrossRefGoogle Scholar
  99. 99.
    Mohapatra BR, Bapuji M, Sree A (2003) Production of industrial enzymes (amylase, carboxymethylcellulase and protease) by bacteria isolated from marine sedentary organizms. Acta Biotechnol 23:75–84CrossRefGoogle Scholar
  100. 100.
    O’Sullivan L, Murphy B, McLoughlin P et al (2010) Prebiotics from marine macroalgae for human and animal health applications. Mar Drugs 8(7):2038–2064.  https://doi.org/10.3390/md8072038 CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Devillé C, Gharbi M, Dandrifosse G, Peulen O (2007) Study on the effects of laminarin, a polysaccharide from seaweed, on gut characteristics. J Sci Food Agric 87:1717–1725CrossRefGoogle Scholar
  102. 102.
    Courtois J (2009) Oligosaccharides from land plants and algae: production and applications in therapeutics and biotechnology. Curr Opin Microbiol 12(3):261–273.  https://doi.org/10.1016/j.mib.2009.04.007 CrossRefPubMedGoogle Scholar
  103. 103.
    Wang Y (2009) Prebiotics: present and future in food science and technology. Food Res Int 42:8–12CrossRefGoogle Scholar
  104. 104.
    Holdt SL, Kraan S (2011) Bioactive compounds in seaweed: functional food applications and legislation. J Appl Phycol 23:543–597CrossRefGoogle Scholar
  105. 105.
    Kim SK, Li YX (2011) Medicinal benefits of sulfated polysaccharides from sea vegetables. Adv Food Nutr Res 64:391–402.  https://doi.org/10.1016/B978-0-12-387669-0.00030-2 CrossRefPubMedGoogle Scholar
  106. 106.
    Ciferri O (1983) Spirulina, the edible microorganism (algae, single-cell protein). Microbiol Rev 47:551–578PubMedPubMedCentralGoogle Scholar
  107. 107.
    Lesser MP (2006) Oxidative stress in marine environments: biochemistry and physiological ecology. Annu Rev Physiol 68:253–278.  https://doi.org/10.1146/annurev.physiol.68.040104.110001 CrossRefPubMedGoogle Scholar
  108. 108.
    Kidd P (2011) Astaxanthin, cell membrane nutrient with diverse clinical benefits and anti-aging potential. Altern Med Rev 16(4):355–364PubMedGoogle Scholar
  109. 109.
    Yang Y, Kim B, Lee JY (2013) Astaxanthin structure, metabolism, and health benefits. J Hum Nutr Food Sci 1(1003):1–11Google Scholar
  110. 110.
    Pashkow FJ, Watumull DG, Campbell CL (2008) Astaxanthin: a novel potential treatment for oxidative stress and inflammation in cardiovascular disease. Am J Cardiol 101(10A):58D–68D.  https://doi.org/10.1016/j.amjcard.2008.02.010 CrossRefPubMedGoogle Scholar
  111. 111.
    Guerin M, Huntley ME, Olaizola M (2003) Haematococcus astaxanthin: applications for human health and nutrition. Trends Biotechnol 21(5):210–216.  https://doi.org/10.1016/S0167-7799(03)00078-7 CrossRefPubMedGoogle Scholar
  112. 112.
    Matsumoto RL, Bastos DH, Mendonca S et al (2009) Effects of mate tea (Ilex paraguariensis) ingestion on mRNA expression of antioxidant enzymes, lipid peroxidation, and total antioxidant status in healthy young women. J Agric Food Chem 57(5):1775–1780.  https://doi.org/10.1021/jf803096g CrossRefPubMedGoogle Scholar
  113. 113.
    Heo SJ, Park EJ, Lee KW, Jeon YJ (2005) Antioxidant activities of enzymatic extracts from brown seaweeds. Bioresour Technol 96(14):1613–1623.  https://doi.org/10.1016/j.biortech.2004.07.013 CrossRefPubMedGoogle Scholar
  114. 114.
    Cofrades S, Lopez-Lopez I, Bravo L et al (2010) Nutritional and antioxidant properties of different brown and red Spanish edible seaweeds. Food Sci Technol Int/Ciencia y tecnologia de los alimentos internacional 16(5):361–370.  https://doi.org/10.1177/1082013210367049 CrossRefPubMedGoogle Scholar
  115. 115.
    Li Y, Qian ZJ, Ryu B, Lee SH, Kim MM, Kim SK (2009) Chemical components and its antioxidant properties in vitro: an edible marine brown alga, Ecklonia cava. Bioorg Med Chem 17(5):1963–1973.  https://doi.org/10.1016/j.bmc.2009.01.031 CrossRefPubMedGoogle Scholar
  116. 116.
    Artan M, Li Y, Karadeniz F, Lee SH, Kim MM, Kim SK (2008) Anti-HIV-1 activity of phloroglucinol derivative, 6,6′-bieckol, from Ecklonia cava. Bioorg Med Chem 16(17):7921–7926.  https://doi.org/10.1016/j.bmc.2008.07.078 CrossRefPubMedGoogle Scholar
  117. 117.
    Kong CS, Kim JA, Yoon NY, Kim SK (2009) Induction of apoptosis by phloroglucinol derivative from Ecklonia cava in MCF-7 human breast cancer cells. Food Chem Toxicol 47(7):1653–1658.  https://doi.org/10.1016/j.fct.2009.04.013 CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Kim SK, Karadeniz F (2012) Biological importance and applications of squalene and squalane. Adv Food Nutr Res 65:223–233.  https://doi.org/10.1016/B978-0-12-416003-3.00014-7 CrossRefPubMedGoogle Scholar
  119. 119.
    Ghimire GP, Lee HC, Sohng JK (2009) Improved squalene production via modulation of the methylerythritol 4-phosphate pathway and heterologous expression of genes from Streptomyces peucetius ATCC 27952 in Escherichia coli. Appl Environ Microbiol 75(22):7291–7293.  https://doi.org/10.1128/AEM.01402-09 CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Mantzouridou F, Naziri E, Tsimidou MZ (2009) Squalene versus ergosterol formation using Saccharomyces cerevisiae: combined effect of oxygen supply, inoculum size, and fermentation time on yield and selectivity of the bioprocess. J Agric Food Chem 57(14):6189–6198.  https://doi.org/10.1021/jf900673n CrossRefPubMedGoogle Scholar
  121. 121.
    Copeman LA, Parrish CC (2004) Lipids classes, fatty acids, and sterols in seafood from Gilbert Bay, Southern Labrador. J Agric Food Chem 52:4872–4881PubMedCrossRefGoogle Scholar
  122. 122.
    Murphy KJ, Mann NJ, Sinclair AJ (2003) Fatty acid and sterol composition of frozen and freeze-dried New Zealand Green Lipped Mussel (Perna canaliculus) from three sites in New Zealand. Asia Pac J Clin Nutr 12(1):50–60PubMedGoogle Scholar
  123. 123.
    Rasmussen HE, Blobaum KR, Jesch ED et al (2009) Hypocholesterolemic effect of Nostoc commune var. sphaeroides Kutzing, an edible blue-green alga. Eur J Nutr 48(7):387–394.  https://doi.org/10.1007/s00394-009-0025-y CrossRefPubMedGoogle Scholar
  124. 124.
    Patridge EV, Gareiss PC, Kinch MS, Hoyer DW (2015) An analysis of original research contributions toward FDA-approved drugs. Drug Discov Today 20(10):1182–1187.  https://doi.org/10.1016/j.drudis.2015.06.006 CrossRefPubMedGoogle Scholar
  125. 125.
    de Goeij BECG, Lambert JM (2016) New developments for antibody-drug conjugate-based therapeutic approaches. Curr Opin Immunol 40:14–23.  https://doi.org/10.1016/j.coi.2016.02.008 CrossRefPubMedGoogle Scholar
  126. 126.
    Gerwick WH, Moore BS (2012) Lessons from the past and charting the future of marine natural products drug discovery and chemical biology (vol 19, pg 85, 2012). Chem Biol 19(12):1631.  https://doi.org/10.1016/j.chembiol.2012.12.004 CrossRefGoogle Scholar
  127. 127.
    Newman DJ, Cragg GM (2014) Marine-sourced anti-cancer and cancer pain control agents in clinical and late preclinical development. Mar Drugs 12(1):255–278.  https://doi.org/10.3390/md12010255 CrossRefPubMedPubMedCentralGoogle Scholar
  128. 128.
    Mayer AMS (2017) Marine pharmaceuticals: the clinical pipeline. http://marinepharmacology.midwestern.edu/clinPipeline.htm. Accessed 30 May 2017
  129. 129.
    FDA (2016) Drugs@FDA: FDA approved drug products. http://www.accessdata.fda.gov/scripts/cder/daf/. Accessed 30 Dec 2016
  130. 130.
  131. 131.
    Lichtman MA (2013) A historical perspective on the development of the cytarabine (7days) and daunorubicin (3days) treatment regimen for acute myelogenous leukemia: 2013 the 40th anniversary of 7+3. Blood Cells Mol Dis 50(2):119–130.  https://doi.org/10.1016/j.bcmd.2012.10.005 CrossRefPubMedGoogle Scholar
  132. 132.
    Shankland KR, Armitage JO, Hancock BW (2012) Non-Hodgkin lymphoma. Lancet 380(9844):848–857.  https://doi.org/10.1016/S0140-6736(12)60605-9 CrossRefPubMedGoogle Scholar
  133. 133.
    Cassidy S, Syed BA (2016) Acute myeloid leukaemia drugs market. Nat Rev Drug Discov 15(8):527–528.  https://doi.org/10.1038/nrd.2016.140 CrossRefPubMedGoogle Scholar
  134. 134.
    Mayer AMS, Glaser KB, Cuevas C et al (2010) The odyssey of marine pharmaceuticals: a current pipeline perspective. Trends Pharmacol Sci 31(6):255–265.  https://doi.org/10.1016/j.tips.2010.02.005 CrossRefPubMedGoogle Scholar
  135. 135.
    Chhikara BS, Parang K (2010) Development of cytarabine prodrugs and delivery systems for leukemia treatment. Expert Opin Drug Del 7(12):1399–1414.  https://doi.org/10.1517/17425247.2010.527330 CrossRefGoogle Scholar
  136. 136.
    Kripp M, Hofheinz RD (2008) Treatment of lymphomatous and leukemic meningitis with liposomal encapsulated cytarabine. Int J Nanomedicine 3(4):397–401PubMedPubMedCentralGoogle Scholar
  137. 137.
    National Cancer Institute. In: Clinical Trials (PDQ®). National Cancer Institute. Accessed 1 Nov 2013Google Scholar
  138. 138.
    Pharma C. Clavis Pharma announces negative outcome of phase III CLAVELA trial with elacytarabine in patients with acute myeloid leukaemia. http://aqualis.no/home. Accessed 1 Nov 2013
  139. 139.
    Gandhi V, Keating MJ, Bate G, Kirkpatrick P (2006) Nelarabine. Nat Rev Drug Discov 5(1):17–18PubMedCrossRefGoogle Scholar
  140. 140.
    Shen W, Kim JS, Kish PE et al (2009) Design and synthesis of vidarabine prodrugs as antiviral agents. Bioorg Med Chem Lett 19(3):792–796.  https://doi.org/10.1016/j.bmcl.2008.12.031 CrossRefPubMedGoogle Scholar
  141. 141.
    Cimino G, Derosa S, Destefano S (1984) Antiviral agents from a Gorgonian, Eunicella-Cavolini. Experientia 40(4):339–340.  https://doi.org/10.1007/Bf01952539 CrossRefGoogle Scholar
  142. 142.
    Montgomery J, Hewson K (1969) Nucleosides of 2-Fluoroadenine. J Med Chem 12(3):498–504PubMedCrossRefGoogle Scholar
  143. 143.
    Robak P, Robak T (2013) Older and new purine nucleoside analogs for patients with acute leukemias. Cancer Treat Rev 39(8):851–861PubMedCrossRefGoogle Scholar
  144. 144.
    Ricci F, Tedeschi A, Morra E, Montillo M (2009) Fludarabine in the treatment of chronic lymphocytic leukemia: a review. Ther Clin Risk Manag 5:187–207PubMedPubMedCentralGoogle Scholar
  145. 145.
    Lapponi MJ, Rivero CW, Zinni MA, Britos CN, Trelles JA (2016) New developments in nucleoside analogues biosynthesis: a review. J Mol Catal B Enzym 133:218–233CrossRefGoogle Scholar
  146. 146.
    Hernandez-Ilizaliturri FJ, Czuczman MS (2009) A review of nelarabine in the treatment of T-cell lymphoblastic leukemia/lymphoma. Clin Med Ther 1:CMT.S1954CrossRefGoogle Scholar
  147. 147.
    Cohen MH, Johnson JR, Justice R, Pazdur R (2008) FDA drug approval summary: nelarabine (Arranon(R)) for the treatment of T-Cell lymphoblastic leukemia/lymphoma. Oncologist 13(6):709–714PubMedCrossRefGoogle Scholar
  148. 148.
    Bauer A, Bronstrupt M (2014) Industrial natural product chemistry for drug discovery and development. Nat Prod Rep 31(1):35–60.  https://doi.org/10.1039/c3np70058e CrossRefPubMedGoogle Scholar
  149. 149.
    Esai C (2016) http://www.eisai.com. Accessed 6 Dec 2016
  150. 150.
    Duggan PJ, Tuck KL (2015) Bioactive mimetics of conotoxins and other venom peptides. Toxins 7(10):4175–4198.  https://doi.org/10.3390/toxins7104175 CrossRefPubMedPubMedCentralGoogle Scholar
  151. 151.
    Nelson L (2004) One slip, and you’re dead…. Nature 429(6994):798–799.  https://doi.org/10.1038/429798a CrossRefPubMedGoogle Scholar
  152. 152.
    Han TS, Teichert RW, Olivera BM, Bulaj G (2008) Conus venoms – a rich source of peptide-based therapeutics. Curr Pharm Des 14(24):2462–2479.  https://doi.org/10.2174/138161208785777469 CrossRefPubMedGoogle Scholar
  153. 153.
    Oliveira BM (2000) ω-conotoxin MVIIA: from marine snail venom to analgesic drug. In: Fusetani N (ed) Drugs from the sea. Karger, Basel; New York, NY, pp 74–85CrossRefGoogle Scholar
  154. 154.
    Bingham JP, Mitsunaga E, Bergeron ZL (2010) Drugs from slugs-past, present and future perspectives of omega-conotoxin research. Chem Biol Interact 183(1):1–18.  https://doi.org/10.1016/j.cbi.2009.09.021 CrossRefPubMedGoogle Scholar
  155. 155.
    Brady RM, Zhang MM, Gable R, Norton RS, Baell JB (2013) De novo design and synthesis of a mu-conotoxin KIIIA peptidomimetic. Bioorg Med Chem Lett 23(17):4892–4895.  https://doi.org/10.1016/j.bmcl.2013.06.086 CrossRefPubMedGoogle Scholar
  156. 156.
    CORDIS (2016) VENOMICS report summary. http://cordis.europa.eu/result/rcn/182082_en.html. Accessed 6 Dec 2016
  157. 157.
    Bays H (2006) Clinical overview of omacor: a concentrated formulation of omega-3 polyunsaturated fatty acids. Am J Cardiol 98(4A):71i–76i.  https://doi.org/10.1016/j.amjcard.2005.12.029 CrossRefPubMedGoogle Scholar
  158. 158.
    Gluck T, Alter P (2016) Marine omega-3 highly unsaturated fatty acids: from mechanisms to clinical implications in heart failure and arrhythmias. Vasc Pharmacol 82:11–19.  https://doi.org/10.1016/j.vph.2016.03.007 CrossRefGoogle Scholar
  159. 159.
    Rupp H (2009) OmacorA (R) (prescription omega-3-acid ethyl esters 90): from severe rhythm disorders to hypertriglyceridemia. Adv Ther 26(7):675–690.  https://doi.org/10.1007/s12325-009-0045-2 CrossRefPubMedGoogle Scholar
  160. 160.
    Koski RR (2008) Omega-3-acid ethyl esters (lovaza) for severe hypertriglyceridemia. Pharm Therap 33(5):271–303Google Scholar
  161. 161.
    Glueck CJ, Khan N, Riaz M, Padda J, Khan Z, Wang P (2012) Titrating lovaza from 4 to 8 to 12 grams/day in patients with primary hypertriglyceridemia who had triglyceride levels > 500 mg/dl despite conventional triglyceride lowering therapy. Lipids Health Dis 11. doi: https://doi.org/10.1186/1476-511x-11-143 CrossRefPubMedPubMedCentralGoogle Scholar
  162. 162.
    Backes J, Anzalone D, Hilleman D, Catini J (2016) The clinical relevance of omega-3 fatty acids in the management of hypertriglyceridemia. Lipids Health Dis 15. doi: https://doi.org/10.1186/S12944-016-0286-4
  163. 163.
    D’Incalci M, Galmarini CM (2010) A review of trabectedin (ET-743): A unique mechanism of action. Mol Cancer Ther 9(8):2157–2163.  https://doi.org/10.1158/1535-7163.MCT-10-0263 CrossRefPubMedGoogle Scholar
  164. 164.
    Larsen AK, Galmarini CM, D’Incalci M (2016) Unique features of trabectedin mechanism of action. Cancer Chemother Pharmacol 77(4):663–671.  https://doi.org/10.1007/s00280-015-2918-1 CrossRefPubMedGoogle Scholar
  165. 165.
    D’Incalci M, Badri N, Galmarini CM, Allavena P (2014) Trabectedin, a drug acting on both cancer cells and the tumour microenvironment. Br J Cancer 111(4):646–650.  https://doi.org/10.1038/bjc.2014.149 CrossRefPubMedPubMedCentralGoogle Scholar
  166. 166.
    Rinehart KL (2000) Antitumor compounds from tunicates. Med Res Rev 20(1):1–27PubMedCrossRefGoogle Scholar
  167. 167.
    Molinski TF, Dalisay DS, Lievens SL, Saludes JP (2009) Drug development from marine natural products. Nat Rev Drug Discov 8(1):69–85.  https://doi.org/10.1038/nrd2487 CrossRefPubMedPubMedCentralGoogle Scholar
  168. 168.
    Cuevas C, Francesch A (2009) Development of Yondelis (R) (trabectedin, ET-743). A semisynthetic process solves the supply problem. Nat Prod Rep 26(3):322–337.  https://doi.org/10.1039/b808331m CrossRefPubMedGoogle Scholar
  169. 169.
    Rinehart KL, Holt TG, Fregeau NL et al (1990) Isolation and characterization of the ecteinascidins, potent antitumor compounds from the Caribbean Tunicate Ecteinascidia-Turbinata. Abstr Pap Am Chem S 200:141-ORGNGoogle Scholar
  170. 170.
    Wright AE, Forleo DA, Gunawardana GP, Gunasekera SP, Koehn FE, Mcconnell OJ (1990) Antitumor tetrahydroisoquinoline alkaloids from the colonial Ascidian Ecteinascidia-Turbinata. J Org Chem 55(15):4508–4512.  https://doi.org/10.1021/Jo00302a006 CrossRefGoogle Scholar
  171. 171.
    Corey EJ, Gin DY, Kania RS (1996) Enantioselective total synthesis of ecteinascidin 743. J Am Chem Soc 118(38):9202–9203.  https://doi.org/10.1021/Ja962480t CrossRefGoogle Scholar
  172. 172.
    Martinez EJ, Corey EJ (2000) A new, more efficient, and effective process for the synthesis of a key pentacyclic intermediate for production of ecteinascidin and phthalascidin antitumor agents. Org Lett 2(7):993–996.  https://doi.org/10.1021/Ol0056729 CrossRefPubMedGoogle Scholar
  173. 173.
    Cuevas C, Perez M, Martin MJ et al (2000) Synthesis of ecteinascidin ET-743 and phthalascidin Pt-650 from cyanosafracin B. Org Lett 2(16):2545–2548.  https://doi.org/10.1021/Ol0062502 CrossRefPubMedGoogle Scholar
  174. 174.
    Velasco IA, De La Calle F, Aparicio PT et al (2004) The gene cluster involved in safracin biosynthesis and its uses for genetic engineering. Google PatentsGoogle Scholar
  175. 175.
    Menchaca R, Martinez V, Rodriguez A et al (2003) Synthesis of natural ecteinascidins (ET-729, ET-745, ET-759B, ET-736, ET-637, ET-594) from cyanosafracin B. J Org Chem 68(23):8859–8866.  https://doi.org/10.1021/jo034547i CrossRefPubMedGoogle Scholar
  176. 176.
    Manzanares I, Cuevas C, García-Nieto R, Marco E, Gago F (2001) Advances in the chemistry and pharmacology of ecteinascidins, a promising new class of anti-cancer agents. Curr Med Chem Anticancer Agents 1(3):257–276.  https://doi.org/10.2174/1568011013354561 CrossRefPubMedGoogle Scholar
  177. 177.
    Goodin S, Barbour S, Song J, Berrak E, Cox D (2015) Safety and tolerability of eribulin mesylate in patients with pretreated metastatic breast cancer. Am J Health-Syst Pharm 72(24):2150–2156.  https://doi.org/10.2146/ajhp140773 CrossRefPubMedGoogle Scholar
  178. 178.
    FDA (2016) FDA approves first drug to show survival benefit in liposarcoma. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm483714.htm. Accessed Dec 2016
  179. 179.
    Bai R, Paull KD, Herald CL, Malspeis L, Pettit GR, Hamel E (1991) Halichondrin-B and homohalichondrin-B, marine natural-products binding in the vinca domain of tubulin – discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data. J Biol Chem 266(24):15882–15889PubMedGoogle Scholar
  180. 180.
    Dybdal-Hargreaves NF, Risinger AL, Mooberry SL (2015) Eribulin Mesylate: mechanism of action of a unique microtubule-targeting agent. Clin Cancer Res 21(11):2445–2452.  https://doi.org/10.1158/1078-0432.CCR-14-3252 CrossRefPubMedPubMedCentralGoogle Scholar
  181. 181.
    Bauer A (2016) Story of Eribulin Mesylate: development of the longest drug synthesis. In: Časar Z (ed) Synthesis of heterocycles in contemporary medicinal chemistry, Topics in heterocyclic chemistry, vol 44. Springer, Switzerland, pp 209–270CrossRefGoogle Scholar
  182. 182.
    Aicher TD, Buszek KR, Fang FG et al (1992) Total synthesis of halichondrin-B and norhalichondrin-B. J Am Chem Soc 114(8):3162–3164.  https://doi.org/10.1021/Ja00034a086 CrossRefGoogle Scholar
  183. 183.
    Towle MJ, Salvato KA, Budrow J et al (2001) In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B. Cancer Res 61(3):1013–1021PubMedGoogle Scholar
  184. 184.
    Yu MJ, Zheng WJ, Seletsky BM (2013) From micrograms to grams: scale-up synthesis of eribulin mesylate. Nat Prod Rep 30(9):1158–1164.  https://doi.org/10.1039/c3np70051h CrossRefPubMedGoogle Scholar
  185. 185.
    Liu KKC, Sakya SM, O’Donnell CJ, Flick AC, Ding HX (2012) Synthetic approaches to the 2010 new drugs. Bioorg Med Chem 20(3):1155–1174.  https://doi.org/10.1016/j.bmc.2011.12.049 CrossRefPubMedGoogle Scholar
  186. 186.
    Newland AM, Li JX, Wasco LE, Aziz MT, Lowe DK (2013) Brentuximab vedotin: a CD30-directed antibody-cytotoxic drug conjugate. Pharmacotherapy 33(1):93–104.  https://doi.org/10.1002/phar.1170 CrossRefPubMedGoogle Scholar
  187. 187.
    Gerber HP, Koehn FE, Abraham RT (2013) The antibody-drug conjugate: an enabling modality for natural product-based cancer therapeutics. Nat Prod Rep 30(5):625–639.  https://doi.org/10.1039/c3np20113a CrossRefPubMedGoogle Scholar
  188. 188.
    Ansell SM (2011) Brentuximab vedotin: delivering an antimitotic drug to activated lymphoma cells. Expert Opin Investig Drugs 20(1):99–105.  https://doi.org/10.1517/13543784.2011.542147 CrossRefPubMedGoogle Scholar
  189. 189.
    Pettit GR, Kamano Y, Herald CL et al (1987) Antineoplastic agents 136. The isolation and structure of a remarkable marine animal antineoplastic constituent – Dolastatin 10. J Am Chem Soc 109(22):6883–6885.  https://doi.org/10.1021/Ja00256a070 CrossRefGoogle Scholar
  190. 190.
    Maderna A, Doroski M, Subramanyam C et al (2014) Discovery of cytotoxic Dolastatin 10 analogues with N-terminal modifications. J Med Chem 57(24):10527–10543.  https://doi.org/10.1021/jm501649k CrossRefPubMedGoogle Scholar
  191. 191.
    Pettit GR, Singh SB, Hogan F et al (1989) Antineoplastic agents 189. The absolute-configuration and synthesis of natural (-)-Dolastatin-10. J Am Chem Soc 111(14):5463–5465.  https://doi.org/10.1021/Ja00196a061 CrossRefGoogle Scholar
  192. 192.
    Luesch H, Moore RE, Paul VJ, Mooberry SL, Corbett TH (2001) Isolation of dolastatin 10 from the marine cyanobacterium Symploca species VP642 and total stereochemistry and biological evaluation of its analogue symplostatin 1. J Nat Prod 64(7):907–910.  https://doi.org/10.1021/np010049y CrossRefPubMedGoogle Scholar
  193. 193.
    Senter PD, Sievers EL (2012) The discovery and development of brentuximab vedotin for use in relapsed Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Nat Biotechnol 30(7):631–637.  https://doi.org/10.1038/nbt.2289 CrossRefPubMedGoogle Scholar
  194. 194.
    FDA (2016) ClinicalTrials.gov. https://clinicaltrials.gov/. Accessed 30 Dec 2016
  195. 195.
    EMA (2016) EU clinical trials register. https://wwwclinicaltrialsregistereu/ctr-search/search. Accessed 30 Dec 2016
  196. 196.
    Leibbrandt A, Meier C, Konig-Schuster M et al (2010) Iota-Carrageenan is a potent inhibitor of influenza A virus infection. PLoS One 5(12).  https://doi.org/10.1371/journal.pone.0014320 PubMedPubMedCentralCrossRefGoogle Scholar
  197. 197.
    Eccles R, Meier C, Jawad M, Weinmullner R, Grassauer A, Prieschl-Grassauer E (2010) Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: a randomized, double-blind, placebo-controlled exploratory study in volunteers with early symptoms of the common cold. Resp Res 11.  https://doi.org/10.1186/1465-9921-11-108
  198. 198.
    Gonzalez ME, Alarcon B, Carrasco L (1987) Polysaccharides as antiviral agents – antiviral activity of Carrageenan. Antimicrob Agents Chemother 31(9):1388–1393PubMedPubMedCentralCrossRefGoogle Scholar
  199. 199.
    Rao MN, Shinnar AE, Noecker LA et al (2000) Aminosterols from the dogfish shark Squalus-acanthias. J Nat Prod 63(5):631–635.  https://doi.org/10.1021/Np990514f CrossRefPubMedGoogle Scholar
  200. 200.
    Noguchi T, Arakawa O (2008) Tetrodotoxin – distribution and accumulation in aquatic organisms, and cases of human intoxication. Mar Drugs 6(2):220–242.  https://doi.org/10.3390/md20080011 CrossRefPubMedPubMedCentralGoogle Scholar
  201. 201.
    Pettit GR, Herald CL, Doubek DL, Herald DL, Arnold E, Clardy J (1982) Anti-neoplastic agents 86. Isolation and structure of bryostatin-1. J Am Chem Soc 104(24):6846–6848.  https://doi.org/10.1021/Ja00388a092 CrossRefGoogle Scholar
  202. 202.
    Martin MJ, Coello L, Fernandez R et al (2013) Isolation and first total synthesis of PM050489 and PM060184, two new marine anticancer compounds. J Am Chem Soc 135(27):10164–10171.  https://doi.org/10.1021/ja404578u CrossRefPubMedGoogle Scholar
  203. 203.
    Feling RH, Buchanan GO, Mincer TJ, Kauffman CA, Jensen PR, Fenical W (2003) Salinosporamide A: a highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus Salinospora. Angew Chem Int Ed 42(3):355.  https://doi.org/10.1002/anie.200390115 CrossRefGoogle Scholar
  204. 204.
    Fenical W, Jensen PR, Cheng XC (2000) Halimide, a cytotoxic marine natural product, and derivatives thereof. Google PatentsGoogle Scholar
  205. 205.
    Kem W, Soti F, Wildeboer K et al (2006) The nemertine toxin anabaseine and its derivative DMXBA (GTS21): chemical and pharmacological properties. Mar Drugs 4(3):255–273.  https://doi.org/10.3390/Md403255 CrossRefPubMedCentralGoogle Scholar
  206. 206.
    Thomas NV, Kim SK (2013) Beneficial effects of marine algal compounds in cosmeceuticals. Mar Drugs 11(1):146–164.  https://doi.org/10.3390/md11010146 CrossRefPubMedPubMedCentralGoogle Scholar
  207. 207.
    Kijjoa ASP (2004) Drugs and cosmetics from the sea. Mar Drugs 2:2CrossRefGoogle Scholar
  208. 208.
    Kim YH, Chung CB, Kim JG et al (2008) Anti-wrinkle activity of ziyuglycoside I isolated from a Sanguisorba officinalis root extract and its application as a cosmeceutical ingredient. Biosci Biotechnol Biochem 72(2):303–311.  https://doi.org/10.1271/bbb.70268 CrossRefPubMedGoogle Scholar
  209. 209.
    Raposo MF, de Morais RM, Bernardo de Morais AM (2013) Bioactivity and applications of sulphated polysaccharides from marine microalgae. Mar Drugs 11(1):233–252.  https://doi.org/10.3390/md11010233 CrossRefPubMedGoogle Scholar
  210. 210.
    LIPOTEC (2016) LIPOTEC CATALOGUE. In: LIPOTEC. http://www.lipotec.com. Accessed 7 Jan 2017
  211. 211.
  212. 212.
    Gupta S, Abu-Ghannam N (2011) Bioactive potential and possible health effects of edible brown seaweeds. Trends Food Sci Technol 22(6):315–326.  https://doi.org/10.1016/j.tifs.2011.03.011 CrossRefGoogle Scholar
  213. 213.
    Li Y-X, Wijesekara I, Li Y, Kim S-K (2011) Phlorotannins as bioactive agents from brown algae. Process Biochem 46(12):2219–2224CrossRefGoogle Scholar
  214. 214.
    Wijesekara I, Pangestuti R, Kim S-K (2011) Biological activities and potential health benefits of sulfated polysaccharides derived from marine algae. Carbohydr Polym 84(1):14–21.  https://doi.org/10.1016/j.carbpol.2010.10.062 CrossRefGoogle Scholar
  215. 215.
    Lee JC, Hou MF, Huang HW et al (2013) Marine algal natural products with anti-oxidative, anti-inflammatory, and anti-cancer properties. Cancer Cell Int 13(1):55.  https://doi.org/10.1186/1475-2867-13-55 CrossRefPubMedPubMedCentralGoogle Scholar
  216. 216.
    SEPPIC (2016) SEPPIC CATALOGUE. In: SEPPIC GROUP. http://www.seppic.com/products-@/3701/view-3708-category.html. Accessed 6 Jan 2016
  217. 217.
    CODIF (2016) DERMOCHLORELLA-D. In: CODIF. http://www.codif-tn.com/en/principesactifs/dermochlorella-d/. Accessed 6 Jan 2017
  218. 218.
    Stolz P, Obermayer B (2005) Manufacturing microalgae for skin care. Cosmet Toilet 120:7Google Scholar
  219. 219.
    GREENSEA (2016) An unlimited mine of innovation. In: GREENSEA. http://greensea.fr/en/active-ingredients. Accessed 6 Jan 2017
  220. 220.
    ALGENIST (2016) Patented breakthrough ingredient. In: ALGENIST. https://algenist.borderfree.com/-ingredient. Accessed 6 Jan 2017
  221. 221.
    FRUTAROM (2016) Frutarom. https://products.frutarom.com/apex/f?p=105:1:0. Accessed 6 Jan 2017
  222. 222.
    Chi Z, Fang Y (2005) Exopolysaccharides from marine bacteria. J Ocean Univ China 4(1):67–74.  https://doi.org/10.1007/s11802-005-0026-2 CrossRefGoogle Scholar
  223. 223.
    Nichols CA, Guezennec J, Bowman JP (2005) Bacterial exopolysaccharides from extreme marine environments with special consideration of the southern ocean, sea ice, and deep-sea hydrothermal vents: a review. Mar Biotechnol (New York, NY) 7(4):253–271.  https://doi.org/10.1007/s10126-004-5118-2 CrossRefGoogle Scholar
  224. 224.
    Cambon-Bonavita MA, Raguenes G, Jean J, Vincent P, Guezennec J (2002) A novel polymer produced by a bacterium isolated from a deep-sea hydrothermal vent polychaete annelid. J Appl Microbiol 93(2):310–315PubMedCrossRefGoogle Scholar
  225. 225.
    Raguenes G, Christen R, Guezennec J, Pignet P, Barbier G (1997) Vibrio diabolicus sp. nov., a new polysaccharide-secreting organism isolated from a deep-sea hydrothermal vent polychaete annelid, Alvinella pompejana. Int J Syst Bacteriol 47(4):989–995.  https://doi.org/10.1099/00207713-47-4-989 CrossRefPubMedGoogle Scholar
  226. 226.
    Raguenes G, Pignet P, Gauthier G et al (1996) Description of a new polymer-secreting bacterium from a deep-sea hydrothermal vent, Alteromonas macleodii subsp. fijiensis, and preliminary characterization of the polymer. Appl Environ Microbiol 62(1):67–73PubMedPubMedCentralGoogle Scholar
  227. 227.
    Raguenes GH, Peres A, Ruimy R et al (1997) Alteromonas infernus sp. nov., a new polysaccharide-producing bacterium isolated from a deep-sea hydrothermal vent. J Appl Microbiol 82(4):422–430PubMedCrossRefGoogle Scholar
  228. 228.
    Rougeaux HG, Guezennec J, Carlson RW, Kervarec N, Pichon R, Talaga P (1999) Structural determination of the exopolysaccharide of Pseudoalteromonas strain HYD 721 isolated from a deep-sea hydrothermal vent. Carbohydr Res 315:12CrossRefGoogle Scholar
  229. 229.
    Vincent P, Pignet P, Talmont F et al (1994) Production and characterization of an exopolysaccharide excreted by a deep-sea hydrothermal vent bacterium isolated from the Polychaete Annelid Alvinella pompejana. Appl Environ Microbiol 60(11):4134–4141PubMedPubMedCentralGoogle Scholar
  230. 230.
    Weiner R, Langille S, Quintero E (1995) Structure, function and immunochemistry of bacterial exopolysaccharides. J Ind Microbiol 15(4):339–346PubMedCrossRefGoogle Scholar
  231. 231.
    Desbruyeres DL, Laubier L (1980) Alvinella pompejana gen. sp. nov., aberrant Ampharetidae from East Pacific Rise hydrothermal vents. Oceanol Acta 3:267–274Google Scholar
  232. 232.
    Le Costaouec T, Cerantola S, Ropartz D et al (2012) Structural data on a bacterial exopolysaccharide produced by a deep-sea Alteromonas macleodii strain. Carbohydr Polym 90(1):49–59.  https://doi.org/10.1016/j.carbpol.2012.04.059 CrossRefPubMedGoogle Scholar
  233. 233.
    Thibodeau AT (2006) The applications and functions of new exopolysaccharide “Deepsane” from the deepest oceans. Fragr J 34:7Google Scholar
  234. 234.
    Potts BC, Faulkner DJ, Jacobs RS (1992) Phospholipase A2 inhibitors from marine organisms. J Nat Prod 55(12):1701–1717PubMedCrossRefGoogle Scholar
  235. 235.
    Day DR, Jabaiah S, Jacobs RS, Little RD (2013) Cyclodextrin formulation of the marine natural product pseudopterosin A uncovers optimal pharmacodynamics in proliferation studies of human umbilical vein endothelial cells. Mar Drugs 11:12CrossRefGoogle Scholar
  236. 236.
    Rouhi AM (2003) Betting on natural products for cures. Chem Eng News 81:10Google Scholar
  237. 237.
    Hee SW, Tsai SH, Chang YC et al (2012) The role of nocturnin in early adipogenesis and modulation of systemic insulin resistance in human. Obesity (Silver Spring, MD) 20(8):1558–1565.  https://doi.org/10.1038/oby.2012.37 CrossRefGoogle Scholar
  238. 238.
    Stubblefield JJ, Terrien J, Green CB (2012) Nocturnin: at the crossroads of clocks and metabolism. Trends Endocrinol Metab 23(7):326–333.  https://doi.org/10.1016/j.tem.2012.03.007 CrossRefPubMedPubMedCentralGoogle Scholar
  239. 239.
    Ivatt RJ (1984) The biology of glycoproteins. Plenum Press, New York, NYCrossRefGoogle Scholar
  240. 240.
    Gottschalk A (1972) Glycoproteins: their composition, structure and function. Elsevier, New York, NYGoogle Scholar
  241. 241.
    Senaratne LS, Park PJ, Kim SK (2006) Isolation and characterization of collagen from brown backed toadfish (Lagocephalus gloveri) skin. Bioresour Technol 97(2):191–197.  https://doi.org/10.1016/j.biortech.2005.02.024 CrossRefPubMedGoogle Scholar
  242. 242.
    Pettit RK (2011) Culturability and secondary metabolite diversity of extreme microbes: expanding contribution of deep sea and deep-sea vent microbes to natural product discovery. Mar Biotechnol 13(1):1–11.  https://doi.org/10.1007/s10126-010-9294-y CrossRefPubMedGoogle Scholar
  243. 243.
    Harvey A (2000) Strategies for discovering drugs from previously unexplored natural products. Drug Discov Today 5(7):294–300.  https://doi.org/10.1016/S1359-6446(00)01511-7 CrossRefPubMedGoogle Scholar
  244. 244.
    Lallier LE, McMeel O, Greiber T, Vanagt T, Dobson ADW, Jaspars M (2014) Access to and use of marine genetic resources: understanding the legal framework. Nat Prod Rep 31(5):612–616.  https://doi.org/10.1039/c3np70123a CrossRefPubMedPubMedCentralGoogle Scholar
  245. 245.
    Dias DA, Urban S, Roessner U (2012) A historical overview of natural products in drug discovery. Metabolites 2(2):303–336PubMedPubMedCentralCrossRefGoogle Scholar
  246. 246.
    Cragg GM, Katz F, David JNA, Rosenthal J (2012) The impact of the United Nations Convention on Biological Diversity on natural products research. Nat Prod Rep 29(12):1407–1423.  https://doi.org/10.1039/c2np20091k CrossRefPubMedPubMedCentralGoogle Scholar
  247. 247.
    Aruoma OI (2006) The impact of food regulation on the food supply chain. Toxicology 221(1):119–127.  https://doi.org/10.1016/j.tox.2005.12.024 CrossRefPubMedGoogle Scholar
  248. 248.
    Byrne D (2003) Health nutrition and labeling. Food Sci Technol 17:26–28Google Scholar
  249. 249.
    David B, Wolfender JL, Dias DA (2015) The pharmaceutical industry and natural products: historical status and new trends. Phytochem Rev 14(2):299–315.  https://doi.org/10.1007/s11101-014-9367-z CrossRefGoogle Scholar
  250. 250.
    Hughes JP, Rees S, Kalindjian SB, Philpott KL (2011) Principles of early drug discovery. Br J Pharmacol 162(6):1239–1249.  https://doi.org/10.1111/j.1476-5381.2010.01127.x CrossRefPubMedPubMedCentralGoogle Scholar
  251. 251.
    Kingston DGI (2011) Modern natural products drug discovery and its relevance to biodiversity conservation. J Nat Prod 74(3):496–511.  https://doi.org/10.1021/np100550t CrossRefPubMedGoogle Scholar
  252. 252.
    Carter GT (2011) Natural products and Pharma 2011: strategic changes spur new opportunities. Nat Prod Rep 28(11):1783–1789.  https://doi.org/10.1039/c1np00033k CrossRefPubMedGoogle Scholar
  253. 253.
    Perez-Victoria I, Martin J, Reyes F (2016) Combined LC/UV/MS and NMR strategies for the dereplication of marine natural products. Planta Med 82(9–10):857–871.  https://doi.org/10.1055/s-0042-101763 CrossRefPubMedGoogle Scholar
  254. 254.
    Radjasa OK, Vaske YM, Navarro G et al (2011) Highlights of marine invertebrate-derived biosynthetic products: their biomedical potential and possible production by microbial associants. Bioorg Med Chem 19(22):6658–6674.  https://doi.org/10.1016/j.bmc.2011.07.017 CrossRefPubMedPubMedCentralGoogle Scholar
  255. 255.
    Hubert J, Nuzillard J-M, Renault J-H (2015) Dereplication strategies in natural product research: how many tools and methodologies behind the same concept? Phytochem Rev.  https://doi.org/10.1007/s11101-015-9448-7
  256. 256.
    Gaudêncio SP, Pereira F (2015) Dereplication: racing to speed up the natural products discovery process. Nat Prod Rep 32(6):779–810.  https://doi.org/10.1039/c4np00134f CrossRefPubMedGoogle Scholar
  257. 257.
    Michel T, Halabalaki M, Skaltsounis AL (2013) New concepts, experimental approaches, and dereplication strategies for the discovery of novel phytoestrogens from natural sources. Planta Med 79(7):514–532.  https://doi.org/10.1055/s-0032-1328300 CrossRefPubMedGoogle Scholar
  258. 258.
    Petersen F, Amstutz R (2008) Natural compounds as drugs. Birkhäuser, BaselCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Ricardo Calado
    • 1
  • Miguel Costa Leal
    • 2
    • 3
  • Helena Gaspar
    • 3
    • 4
  • Susana Santos
    • 4
  • António Marques
    • 5
    • 6
  • Maria Leonor Nunes
    • 6
    • 7
  • Helena Vieira
    • 8
  1. 1.Departamento de Biologia & CESAM & ECOMAREUniversidade de AveiroAveiroPortugal
  2. 2.Department of Fish Ecology and EvolutionEawag: Swiss Federal Institute of Aquatic Science and Technology, Centre for Ecology, Evolution and BiogeochemistryKastanienbaumSwitzerland
  3. 3.MARE – Centro de Ciências do Mar e do Ambiente, Faculdade de CiênciasUniversidade de LisboaLisboaPortugal
  4. 4.Centro de Química e Bioquímica (CQB), Departamento de Química e Bioquímica, Faculdade de CiênciasUniversidade de LisboaLisboaPortugal
  5. 5.Division of Aquaculture and Seafood UpgradingPortuguese Institute for the Sea and Atmosphere, IPMALisboaPortugal
  6. 6.CIIMAR, Novo Edifício do Terminal de Cruzeiros do Porto de LeixõesMatosinhosPortugal
  7. 7.Universidade Lusófona de Humanidades e TecnologiasLisboaPortugal
  8. 8.Faculdade de Ciências, Biosystems and Integrative Sciences Institute (BioISI), Universidade de Lisboa, Edificio TecLabsLisboaPortugal

Personalised recommendations