بسم هللا الرحمن الرحيم PHG 322 PHARMACOGONSY II LECTURE 6 PRESENTED BY ASSISTANT PROF. DR. EBTESAM ALSHEDDI 6 kingdoms of marine organisms • Bacteria are single-celled organisms that reproduce by splitting in two. Bacteria live throughout the marine environment. They play a crucial role in ecosystems, breaking down organic material and making nutrients available for the phytoplankton. • Protozoans are single-celled organisms that are generally much larger than bacteria. They may be autotrophic or heterotrophic. In the marine environment, this kingdom is well represented and includes amoebae. • Chromists range from very small organisms such as diatoms (a type of phytoplankton) to seaweeds. Most chromists photosynthesise but there are some significant differences that have led scientists to classify them separately to plants, for example, they use a different kind of chlorophyll. • Fungi rely on breaking down organic material as they are not able to make their own food. There are very few fungi in the marine environment. • Plants are multi-cellular and autotrophic – they use photosynthesis to produce food using sunlight. Plants are much more widespread on land and in freshwater, and there are only a few types that thrive in the marine environment, for example, eel grass and mangroves. Seaweeds were previously classed as plants before they were reclassified as chromists. • Animals are typically large and multi-cellular. They are heterotrophic and rely on other organisms for food. Animals in the marine environment include jellyfish, sponges, sea spiders, bryozoans, mussels, sea stars, fish and whales. Sources of marine bioactive compounds include: Marine algae (= Seaweeds) 3 Marine bacteria and fungi Marine invertebrates Marine algae • Grow almost exclusively in the shallow waters at the edge of the world's oceans • Seaweeds are plants because they use the sun's energy to produce carbohydrates from carbon dioxide and water. • They are simpler than the land plants mainly because they absorb the nutrients that they require from the surrounding water and have no need for roots or complex conducting tissues • Seaweed draws an extraordinary wealth of mineral elements from the sea which includes sodium, calcium, magnesium, potassium, chlorine, sulfur and phosphorus; the micronutrients include iodine, iron, zinc, copper, selenium, molybdenum, fluoride, manganese, boron, nickel and cobalt • vitamins like carotenes (provitamin A); vitamin C, B12 along with higher proportion of essential fatty acids than land plants. Marine algae (cont.): Can be classified into three broad groups based on their color: (= Phaeophyceae) (= Rhodophyceae) Brown seaweeds Red seaweeds (= Chlorophyceae) Green seaweeds Are usually large Are usually smaller Also small Range from: - Giant size (20 m long) Range from: - Few centimeters to about 1 m in length Similar in size to red seaweeds - 5 Thick, leatherlike seaweeds from 2 – 4 m long Small species 30 – 60 cm long Not always red, sometimes purple Brown algae Red algae Green algae Seaweeds are also called “macroalgae”. This distinguishes them from “microalgae” which are: - Microscopic in size - Often unicellular and - Are best known by the “blue-green” algae that contaminate rivers and streams. Cyanobacteria (blue-green algae) are microorganisms that structurally resemble bacteria (they lack a nucleus and organelles ). However, unlike other bacteria, cyanobacteria contain chlorophyll a and conduct oxygenic photosynthesis Phycology (from Greek, phykos, "seaweed” and -logia) is the 7 scientific study of algae. Sources of bioactive compounds (cont.): 2) Marine bacteria and fungi: Of considerable importance as new promising sources of biologically active products. Up till now, only a small number of microorganisms have been investigated, yet a huge number of active substances have been isolated e.g. some antibiotics. 8 • It was surprising to find that many bioactive compounds, reported from marine invertebrates are produced by their microbial symbionts • Interestingly microorganisms associated with marine invertebrates are proved valuable candidates for drug discovery program Sources of bioactive compounds (cont.): 3) Marine invertebrates: They are animals that inhabit a marine environment and are, lacking a vertebral column. In order to protect themselves, they may have evolved a shell or a hard exoskeleton, but this is not always the case. Bioactive metabolites have been isolated from many invertebrates among these are: marine sponges, jellyfish, tunicates, bryozoans, sea hare and others. 10 Marine sponges: They are sessile animals that filter water through their porous bodies. They ingest food particles and dissolved materials. Marine sponges known to be a very rich source of terpenoids , halogenated alkaloids and Polyacetylenenic alcohols Jellyfish: They are free-swimming animal. The body of the jellyfish consists of more than 95% of water and less than 5% of organic matter. When removed from water, they collapse completely. 11 Tunicates: Their body is a sack with two siphons through which water enters and exits. Water is filtered inside the sack- shaped body. Bryozoans: They are living for the most part in colonies of interconnected individuals. 12 Sea hare: The common name is derived from: - The two long rhinophores that project upwards from their heads → They resemble the ears of a hare 13 Biomedical potential of marine natural products: In recent years, published reviews clearly indicate the tremendous potential of marine organisms as a source of new pharmaceuticals. Classes of bioactive compounds include: 1) Antiviral substances 2) Cytotoxic compounds 3) Antiparasitic compounds 4) Anticoagulants 14 Classes of bioactive compounds include: (cont.) 5) Antimicrobial agents 6) Anti-inflammatory compounds 7) Toxins 15 Some of the commercialized products Vidarabine • Also known Ara-A • From sponge • Nucleoside it combines a adenosine base with an arabinose sugar • Antiviral (herpes virus) cytarabine • also known as Ara-C (Arabinofuranosyl Cytidine). • From sponge • it combines a cytosine base with an arabinose sugar • Anticancer Kainic acid • Anthelmintic • From seaweed Ziconotide • From cone snail • Peptide • Analgesic Eribulin • From sponge • Anticancer • Macrolide Lovaza • From fish • Omega-3-fatty acid • Hypertriglyceride Trabectedin • From tunicate • Alkaloid • Anticancer Antiviral compounds • From sponge • The search for new antiviral agents from marine sources particularly sponges yielded several promising therapeutic leads. 1. Ara-A (Adenine arabinoside): • Vidarabine or Ara-A is a synthetic analogue of spongouridine with improved antiviral activity. • Spongouridine isolated from the Caribbean sponge Tethya crypta • Vidarabine is an inhibitor of viral DNA synthesis • Active against Herpes viruses Antiviral • 2- Avarol and avarone • • • • a sesquiterpenoid hydroquinone or quinone isolated from the marine sponge Disidea avara inhibitory effect on the replication of the etiologic agent of Acquired Immune Deficiency Syndrome (AIDS) Avarol Avarone Antiviral • From tunicate • 1- Patellazole B: A thiazole-containing macrolide. It showed very potent in vitro activity against Herpes simplex viruses. It was isolated from the tunicate Lissoclinum patella. Antiviral • 2- Didemnins • • • • are cyclic depsipeptide compounds isolated from a tunicate (sea-squirt) of the genus Trididemnum Active against herpes simplex virus type 1 Didemnin B also showed antitumor activity antiviral • 3- Eudistomins • Isolated from Eudistoma olivaceum • A family of β-carbolines Antiviral • From seaweed • 1- sulphated fucan • • • • isolated from the brown seaweed Cystoseira indica Are polysaccharide have potent antiviral activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) Antiviral • 2- Sphingosine derivative • an 18-carbon amino alcohol