New Medicines from the Sea Flashcards
Definition for a drug
A drug is any substance presented for treating, curing or preventing disease in human beings or in animals.
A drug may also be used for making a medical diagnosis or for restoring, correcting, or modifying physiological functions (e.g., the contraceptive pill).
Definition for a pharmaceutical
A pharmaceutical = a medicinal drug
Definition for a natural product
A natural product is a low molecular weight compound produced by living organisms, usually a secondary metabolite with biologically active properties
Why is there an increasing effort into searching for new medicines in the sea?
There is intense interest in searching for new medicines from marine organisms because:
There is great biodiversity (and therefore chemical diversity) in the oceans
Many compounds are biologically active since they are soluble in water (whihc they need to be to disperse through the body), and produced to provide specific biological functions such as
Chemical defense
Chemical attack eg. For immobilising prey
Chemical communication
What percentage of marketed drugs are derived form natural products?
Over 50% of marketed drugs are derived from natural products
Extracted
Produced by synthesis using np as templates or starting materials
Who was Ernst Haeckel?
Eminent German naturalist artist and philosopher
Discovered, described and named thousands of new species (1850s to 1880s)
Coined the terms
Ecology, Phylum, Phylogeny
What are some of Haeckels sucesses?
Haeckel also proposed the idea that all multicellular animals derived from a theoretical two-layered (ectoderm and endoderm) animal, the Gastraea, a theory that provoked much discussion. He engaged in much valuable research on marine invertebrates, such as the radiolarians, jellyfish, calcareous sponges, and medusae, and wrote a series of monographs on these groups based largely on specimens brought back by the Challenger Expedition of 1872 to 1876.
He was the first to divide the animal kingdom into unicellular and multicellular animals. An ardent Darwinist, Haeckel made several zoological expeditions and founded the Phyletic Museum at Jena and the Ernst Haeckel Haus, which contains his books, records, and other effects.
Give some examples of new phyla being discovered.
Loricifera tiny rotifer like animals which live amongst grains of sand (1983)
Cicliophora – weird tiny animal living on the end of a lobsters lips discovered in 1995.
2006 Xenoturbellid worm
What drug leads are being developed from marine sources to tackle HIV?
Natural products with anti-HIV activity from marine organisms.
Tziveleka et al 2003
Marine biodiversity also offers some possible leads for new drugs to treat the human immunodeficiency virus (HIV).
Currently, more than 150 natural products with promising levels of anti-HIV activity have been isolated from marine organisms.
These include
- cyanovirin-N, a protein from a blue green alga; various sulfated polysaccharides extracted from seaweeds (i.e. Nothogenia fastigiata and Aghardhiella tenera);
- the peptides tachyplesin and polyphemusin, which are highly abundant in hemocyte debris of the horseshoe crabs Tachypleus tridentatus and Limulus polyphemus;
- sponge metabolites such as avarol, avarone, ilimaquinone and several phloroglucinols;
- and a number of metabolites from marine fungi such as equisetin, phomasetin, and integric acid.
- Researchers are also examining the possibility of developing new drugs for treating HIV- and AIDS-related conditions from marine sponges [37].
What is aquapharm?
The company’s goal is to harness this resource to rapidly develop next generation pharmaceuticals and novel, naturally derived functional food and personal care ingredients and products.
Founded in Scotland in 2000, Aquapharm Bio-Discovery is one of the first UK marine biotechnology companies that provides new ‘bio-prospecting’ approaches to source novel natural products from marine microbes.
Started by Andrew Spragg in 2000
Has raised more than £7m financing
Recent refinancing with £4m
Marine fungal peptide
Review of mangroves
study
- Bibi et al (2019)
- 27/84 mangrove species were found to be traditionally used, but not all were validated. The most common pharmacological uses from mangroves are as antioxidants, antimicrobials and antidiabetics.
- Tha plants are mostly used in Asian countries.
- Acanthus ilicifolius is used to treat a plethora of illnesses, such as athma, leprosy, snake bites and more, depending on which bit of the plant is used. There is also a ribose derivative from this species which is called 2-benzoxazoline, which exhibited antiviral and antitumor activities
- Rhizophora mucronata is found in East Africa, Australia and the Indian ocean, and is made of up to 70% tannins. This high percentage of tannins, which produce novel proteins, are responsible for aiding treatment of many health issues, such as rheumatoid arthritis, diabetes and high blood pressure. In New Guinea, its used to cute and treat fertility and menstruation disorders.
- R. mucronata is considered to be an excellent anti-diabetic due to the presence of phenolics, flavonoids, gallic acid, quercetin and coumarin. The bioactive compounds in the species are able to boost insulin production and reduce the blood sugar level.
Marine pharmacology
review
Malve (2016) – Exploring the ocean for new drug developments: Marine pharmacology
- Review of the drugs developed from the marine origin and potential new sources.
- The modern-day focus on marine pharmacology is on microbes, and the active substances they produce can be used to treat severe human diseases.
- Marine natural products are normally secondary metabolites, meaning they have no primary function for the producer relating to growth and reproduction.
- Marine molecules used in medicine can be accepted by humans with minimal manipulations needed.
- India has many institutes along its 8000km diverse coastline, including the National Institute of Oceanology, Goa and Central Drug Research Institute, Lucknow, which are all working towards finding new drugs from marine sources.
• This review classifies the actions of the different types of drugs, including: antibacterial drugs; anti-inflammatory drugs; neuroprotective drugs; antiparasitic drugs; antiviral drugs; analgesic drugs; antimicrobial drugs and antimalarial drugs.
• EG. South Indian green seaweed Ulva reticulata has been shown to be successful as a neuroinhibitory drug, and can inhibit acetyl-and butyryl-cholinesterase’s, which have the same effect as drugs which are currently used to treat Alzheimer’s.
• There are only 3 marine-derived drugs that have been approved for use by the FDA in America. This is cytarabine (ara-C), vidarabine (ara-A) and ziconotide (prialt).
•
• IT explores the different limiting factors for the development of new drugs from marine sources. This includes the supply, the formulation, the pharmacogenetics (may be difficult to understand phenotypic variation in the molecules), and toxicities of the molecule.
jellyfish collagen
Widdowson & Mearns-Spragg et al (2017) - In vivo comparison of jellyfish and collagen sponges as prototype medical devices-
- Jellyfish collagen is safer as it reduces the transmission risk of bovine spongiform encephalopathy (mad cow disease).
- Compare collagen implantable sponges from Rhizostoma Pumlo jellyfish to bovine.
- Good acceptance of the jellyfish collagen. There was no infections/cell death and inflammation dropped throughout the study as the foreign body was reabsorbed into the rat.
- Founded 2015
Collagen – triple helical scaffold
Collagen in jellyfish is very ancestral – so shares characteristics to all types of human collagen
Chemically non-toxic and chemically versatile
- Traditional collagen comes from cow and pig or rat tail – however disease risk means it cannot be transferred to human.
Jellyfish
Complex physiology leads to variation in the product – cow yeild of collagen is hard to contoll
Jellyfish are every simple
- Jellyfish is inert and cleaner than when compared to other collagen, prion and disease free
Jellies taking the nice of finfish – jelly blooms are so big they can restrict movement of finfish
Products
Biomaterial
2D coated collagen plates
Jellagen 3D scaffolds
Collagen hydrogels
- Markets
Biotech and pharmaceutical industry – drug development and cell culture (growth of
More precise – neuroscience
By plating
IN vitro disease models
Cells cultures on jellagen does not create an immune response, or cause upregulation
May allow translation into human cells
Creates a 3D gell, which is a growth medium allowing cells to be studied in a 3D environment
Unique characteristics – biocompatable, batch batch conisstent
Non pro-infalmmatory
Clean and inert
JellaGel
Chemically defined
Provides biocompatable
Able to be worked at room temperature
Tunable
memory and depression
study
Bryostatins are a group of macrolide lactones from the marine organism Bugula neritina that were first collected and provided to JL Hartwell’s anticancer drug discovery group at the National Cancer Institute (NCI) by Jack Rudloe.[1] Bryostatins are potent modulators of protein kinase C. They have been studied in clinical trials as anti-cancer agents, as anti-AIDS/HIV agents and in people with Alzheimer’s disease.
Sun & Alkon (2005)- Dual effects of bryostatin-1 on spatial memory and depression:
• Dementia and depression share aspects of their manifestation and molecular mechanisms.
• Shows that the use of bryostatin-1 improved the memory capacity of rats in a water maze tank.
• It also showed to work as an antidepressant.
• This supported the hypothesis that formation of memories and mood regulation share common and similar neural mechanisms, and that this type of medication may be the most effective way to fight against depression associated with memory loss.
• Reduced PKC activity is associated with Alzheimer’s and suicide victims.
antibacterial sea sponge
study
Afifi & Khabour (2017)- Antibacterial Activity of the Saudi Red Sea Sponges Against Gram-positive Pathogens:
• Sponges from the phylum porifera have the ability to produce a wide range of bioactive secondary metabolites which can be used in drug applications.
• Several medications derived from sponges are currently available in the market whilst there are many others, such as cytarabine, which are undergoing clinical trials.
• This study took extracts from 9 different species of red sea sponge and tested their antibacterial ability against different human and marine bacterial strains.
• They tested the 9 sea sponges against three strains of bacteria: Bacillus subtilis, Staphylococcus aureus and E.coli.
• All tested extracts showed no activity against E.coli
• C. siphonella showed a moderate-good activity against B. subtilis.
• Against marine bacteria, Callyspongia siphonella showed strong activity against Gram-positive Bacillus sp. (11mm inhibition zone) compared to Gram-positive Staphycoccus spp. (9mm inhibition zone).
• Gram-negative pathogens are resistant to sponge bioactive compounds.
• The results showed that the sponges were able to kill bacteria from their natural habitats, meaning they can protect themselves from microbial pathogens in the wild.
• However, was only tested on 3 pathogens. They may have a stronger antimicrobial effect on other pathogen types.
• Could also try different sponge types
