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Overview of Marine-Derived Medicines
The ocean constitutes more than 70% of planet Earth and represents the largest habitat on our planet.1 In this enormous area, only 5% of the seabed has been explored in some way and less than 0.01% has been exhaustively studied.1
In recent decades, the marine environment has been the subject of great attention from researchers, as it is abundant in compounds relevant to many industries, such as pharmaceuticals, cosmetics, and nutraceuticals, among others.2 This habitat is very competitive and aggressive and therefore requires the production of potent active molecules that can be used to create vaccines, medicines, and supplements, including polyunsaturated fatty acids (PUFAs), polysaccharides, minerals and vitamins, enzymes, and bioactive peptides.1 Furthermore, marine natural resources have an enormous diversity of molecular targets with remarkable selectivity, which increases their pharmacological and therapeutic power.1 Medicine has been exploring the benefits of marine organisms for thousands of years, as their secondary metabolites constitute a vast library of relevant bioactivity².
The ocean is the largest source of potential medicines, with over a million chemical substances already discovered to date³.
Challenges and solutions in ocean exploration
Although significant biological activities have been demonstrated for various health problems², many challenges remain in exploring the potential of marine organisms for medicinal purposes, since the lack of accessibility to deep-sea areas is a barrier to the collection, research, and development of many new and extremely potent marine active components³. Furthermore, the fact that marine resources live in extreme conditions leads to variations in the metabolites produced³. However, reliable autonomous diving techniques have been improved, allowing for an increasing collection of deep-sea marine organisms³. Furthermore, the evolution of mariculture and aquaculture techniques, the optimization of screening programs, and the development of scalable methods for obtaining and separating metabolites are factors that have facilitated the use of these biomasses3. This has led to a large increase in the discovery of new marine products and their testing in clinical trials3. In addition, there is an increase in patent applications for isolated agents with therapeutic activity from marine microorganisms, phytoplankton, algae, sponges, cnidarians, bryozoans, mollusks, tunicates, echinoderms, mangroves, and other plants3. Regarding patents related to marine natural products, approximately 200 were issued for industrial applications between 1969 and 1995, and 45 for therapeutic applications between 2015 and June 2018.
About marine organisms and bioactive compounds
Marine organisms are divided into marine bacteria, cyanobacteria, microalgae, macroalgae, marine fungi, marine invertebrates, and marine fish. The study of these organisms has significantly increased the number of known natural products and plays an important role in the creation of new medicines and the development of the pharmaceutical industry worldwide. Marine compounds have already demonstrated various therapeutic activities, including antibacterial, antiviral, antimalarial, anti-inflammatory, immunosuppressive, analgesic, antioxidant, antitumor, and cardiovascular health-promoting properties.
Pharmaceutical Applications of Marine Bioactive Compounds – A Brief Overview
It was in 1940 that the cephalosporin class of antibiotics was discovered, with cephalosporin C, an antibiotic related to penicillin and produced from the fungus Acremonium chrysogenum, found in the Mediterranean Sea, near Sardinia1,4. But it was only in the 1950s that the boom in the development of marine medicines occurred, marked by Werner Bergmann’s discovery of spongothymidine and spongoiridine, derived from the Caribbean sponge Tectitethya crypta (formerly known as Cryptotethia crypta)2, 9, 10. This gave rise to cytarabine (also known as Ara-C, Cytosar-U®), the first marine-derived drug placed on the market, an anticancer drug that was approved by the US Food and Drug Administration (FDA) only in 1969, for the treatment of leukemia8 10. Later, in 1976, vidarabine (Ara-A, Vira-A®), an antiviral drug derived from arabinose nucleosides isolated from the shallow-water marine sponge Tethya crypta, off the coast of Florida, was approved for the treatment of Herpes simplex virus1 4 10. After that, for different reasons, such The emergence of simple and economically viable synthetic combinations and the failure of some clinical developments caused investment from large pharmaceutical companies to decline at a certain point, leading to skepticism within the scientific community regarding the exploration of new natural products.
There are also many excipients of marine origin on the market. Examples include agar, derived from the red algae Gelidium amansii; alginates, derived from the brown algae Laminaria hyperborea; carrageenans, derived from red algae of the genera Kappaphycus and Eucheuma; fucoidans, derived from brown algae such as Fucus vesiculosus and Sargassum stenophyllum; and chitosan, derived from the exoskeletons of arthropods and crustaceans.<sup>5</sup> Some of these, particularly alginates, are extremely important in the manufacture of medicines, since synthetic substances to replace them have rarely been discovered.<sup>5</sup> In addition, marine collagen from fish has emerged as a versatile and sustainable resource, an alternative to mammalian collagen, due to its lower risk of transmissible diseases to humans, as it can be obtained from waste from the fish processing industry, making the sector more sustainable,<sup>6</sup> and is also free from ethical and religious issues.
Marine Biotechnology Today
Recently, large-scale marine biotechnology projects have been launched outside the EU (e.g., in Norway and South Korea), while in the US institutional funding has decreased in recent years.2 In the EU, the Horizon 2020 program has invested heavily in marine research and innovation, and there are several ongoing marine biotechnology projects based on drug discovery, for example: MAREX – Exploring marine resources for bioactive compounds: from discovery to sustainable production and industrial applications (2010-2014); BAMMBO – Sustainable production of biologically active molecules of marine origin (2011–2014); PharmaSea – Increasing value and flow in the marine biodiscovery pipeline (2012–2016); SeaBioTech – From the seabed to the test bench: harnessing the potential of marine microbes for industrial biotechnology (2012–2016)2. The French ECIMAR program studied marine chemical ecology as an indicator of biodiversity, and the SPECIAL and SPONGES projects specialized in research on marine sponges, while SWAFAX and HYFFI specialized in bioactive compounds from seaweed.2
Obstacles for the pharmaceutical industry
One of the main barriers to the development of drugs from marine organisms is the lack of permanent availability of sufficient quantities of compounds in the marine environment, guaranteeing sustainable use.1 7 This has already interrupted the development of several highly promising marine compounds.1 Another barrier is the fact that, most of the time, the compound of interest is present in small quantities and is difficult to isolate,1 7 as is the case with the extraction of marine invertebrates.1 The difficulty in sustainably harvesting from the marine environment could be solved by breeding marine organisms under ideal conditions,7 exploring mariculture and aquaculture.1 However, it is not yet possible to artificially cultivate many organisms of pharmacological interest, especially microorganisms, due to a lack of knowledge of living conditions in the natural environment and adaptation to cultivation methods.
Co-cultivation of several organisms can be a solution in some cases, as it allows mimicking the complexity found in the natural environment1.
Genetic techniques to increase the yield of production of substances of interest have been optimized to achieve the isolation and expression of genes from organisms that cannot be cultivated. As mentioned earlier, there are several challenges in the identification, development, and commercialization of drugs.
However, there are numerous substances in pre-clinical and clinical trials for the treatment of various diseases, and here the class of antitumor drugs stands out.
It is still necessary to develop technologies that allow for the correct and meticulous assessment of the biodiversity available in the oceans to overcome the obstacles to the development of marine-derived drugs. Advanced molecular techniques have enabled the taxonomic and physiological characterization of organisms, and sampling techniques have been presented as a solution for accessing organism samples to facilitate the cultivation of marine species. However, limitations still exist in the knowledge of organisms and their metabolites for the large-scale implementation of artificial cultivation.
The role of B2E in the sector’s development
At B2E, we act as facilitators of innovation, taking innovative ideas to higher levels of maturity and valuation in different markets, while simultaneously establishing the necessary translation efforts between academic and industrial languages, thus galvanizing the relationship between these sectors. B2E is strategically positioned to stimulate the sustainable development of the Brazilian Blue Bioeconomy, acting specifically in the area of marine biotechnology, as well as in aquaculture and the valorization of marine living resources, B2E is a valuable player in stimulating R&D in marine-derived medicines, acting as a bridge between Portuguese research and national and international markets. In fact, for B2E’s three areas of action, we aim to stimulate the internationalization of national scientific and technological capacity.
Our activity is driven not only by a team of employees with diverse skills, but also by an invaluable network of associates who strategically cover the entire value chain of B2E’s areas of activity – this fruitful interaction with our associates has been successful in propelling us into the spotlight, and the B2E name is beginning to gain some notoriety. Therefore, if you work in biotechnology and would like to boost your business, talk to us!
B2E is a leading company in aquaculture and the valorization of marine living resources. Conclusions: Marine Biotechnology as a Fundamental and Growing Sector
Each year, the number of known marine natural products increases2 8 9. Different factors, such as the development of reliable autonomous diving techniques and deep-sea equipment, human resistance to medications, consumer preferences, or the recognition of the advantages of marine biomass, have motivated the growing interest in research into new alternative medicines from marine living resources in recent years2. This has encouraged the development of new drugs and led to the development of several clinical trials1. Marine invertebrates are one of the main groups of biological organisms that have given rise to secondary metabolites with pharmacological properties and have led to the formulation of new drugs10. Compounds with potential activity in chronic and/or untreated diseases are the most studied for the development of new drugs1. There is increasing investment in research and the emergence of small biotechnology companies that explore the commercialization of these products2, which can be leveraged with the help of B2E.
1. Machado, M., (2019) Organismos Marinhos como Fonte de Novos Fármacos. Thesis, University of Lisbon, Portugal.
2. Kiuru, P., D’Auria, V., Muller, C., Tammela, P., Vu0orela, H., Yli-Kauhaluoma, J. (2014) Exploring Marine Resources for Bioactive Compounds. Planta Med 2014. 80, 1234-1246. DOI: 10.1055/s-0034-1383001
3. Shindre, P., Banerjee, P., Mandhare, A. (2019) Marine natural products as source of new drugs: a patent review (2015-2018). Expert Opinion on Therapeutic Patents. 29, 4, 283-309. ISSN: 1354-3776 (Print) 1744-7674 (Online). DOI: 10.1080/13543776.2019.1598972
4. Sruthi, V., Grace, N., Monica, N., Kumar, V. (2020) Marine pharmacology: an ocean to explore novel drugs. International Journal of Basic & Clinical Pharmacology. 9, 5, 822-828. pISSN 2319-2003 | eISSN 2279-0780. DOI: 10.18203/2319-2003.ijbcp20201767
5. Sabalingam, S., Jayasuriya, W. (2019) Pharmaceutical Excipients of Marine and Animal origin: A Review. Biological and Chemical Research. 6, 184-196. ISSN 2312-0088
6. Salvatore, L., Gallo, N., Natali, M., Campa, L., Lunetti, P., Madaghiele, M., Blasi, F., Corallo, A., Capobianco, L, Sannino, A. (2020) Marine collagen and its derivatives: Versatile and sustainable bio-resources for healthcare. Materials Science & Engineering C. 113 – 110963. DOI: 10.1016/j.msec.2020.110963
7. Alves, A., Sousa, E., Kijjoa, A., Pinto, M. (2020) Marine-Derived Compounds with Potential Use as Cosmeceuticals and Nutricosmetics. Molecules. 25, 2536. DOI: 10.3390/molecules25112536
8. Dyshlovoy, S., Honecker, F. (2020) Marine Compounds and Cancer: The First Two Decades of XXI Century. Marine Drugs. 18, 20. DOI: 10.3390/md18010020
9. Stonik, V. (2009) Marine Natural Products: A Way to New Drugs. ACTA NATURAE. 2
10. Perdicaris, S., Vlachogianni, T., Valavanidis, A. (2013) Bioactive Natural Substances from Marine Sponges: New Developments and Prospects for Future Pharmaceuticals. Natural Products Chemistry & Research. 1, 3. DOI: 10.4172/2329-6836.1000114
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