STRATEGIES FOR THE DISCOVERY OF MARINE DRUGS

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Coral reef

Coral reefs are among the most productive and biologically diverse ecosystems on Earth (Odum and Odum, 1955. The coral reef ecosystem is a diverse collection of species that interact with each other and the physical environment. The sun is the initial source of energy for this ecosystem (Figure 2.5). Through photosynthesis, phytoplankton, algae, and other plants convert light energy into chemical energy (Kadow, 2001). A coral polyp is a tubular saclike animal with a central mouth surrounded by one or more rings of gelatinous tentacles. Depending on the species, coral polyps measure anywhere from a few millimeters to several centimeters in diameter. Those small animals are extremely simple, composed of just two layers of cells. Corals often live in colonies, which also vary in size. Small colonies of only 25 cm exist alongside larger coral colonies reaching a height of 3-4 meters. The end opposite the tentacles, called the base, is attached to a substrate. The tentacles contain microscopic stinging capsules called nematocysts. A nematocyst is a globular structure containing a venom-filled thread with a minute barb at its tip. A tiny sensor projects outside the nemocyst. When the sensor is stimulated physically or chemically, the capsule explodes and ejects the thread with considerable force and speed. The barb penetrates the victim’s skin and injects the venom. The external stimulus causes the mouth to open and the food particles are swept into the stomach cavity by the nematocyst filament, tentacles, or cilia ( Jones et al., 1973).
Most reef-building corals have a mutually beneficial relationship with microscopic unicellular algae called zooxanthellae that live within the cells of the coral’s gastrodermis. As much as 90% of the organic material the algae manufacture photo synthetically is transferred to the host coral tissue. The mutualistic relationship between corals and their algal endosymbionts is a key factor in the evolutionary success of hermatypic (reef building) corals (Muller-Parker and D‘Elia, 1997). Reefs are considered « medicine cabinets » of the future. it Considered « medicine cabinets » of the future, coral reef organisms hold great promise for pharmaceuticals including anti-cancer and anti-inflammatory drugs. The pharmaceutical industry has discovered potentially useful substances with anticancer, AIDS inhibiting, antimicrobial, anti-inflammatory and anticoagulating properties among the seaweeds, sponges, molluscs, corals soft-corals (order Alcyonacea) and gorgonians (order Gorgonacea) and sea anemones of the reefs (Sorokin, 1993; Carte´, 1996; Birkeland, 1997a). It has been claimed that the discovery of prostaglandins in many of the gorgonians in the early 1970s was responsible for the expansion of marine natural products (Carte´, 1996). Many species of seaweed are collected from reefs to be used in the production of agar and carrageenan (Birkeland, 1997a) and as manure (Craik et al., 1990), and coral skeletons have proven to be promising in bone graft operations (Spurgeon, 1992).

Biological activities of the red algae

Some red algae species exhibit both ant nociceptive and anti-inflammatory effects. For example, a methanol extract of Bryothamnion triquetrum (Cavalcante-Silva et al., 1992) had both antinociceptive and anti-inflammatory properties in experiments that used Swiss mice. Antinociceptive activity was examined using an acetic acid-induced writhing test, a hot-plate test, and glutamate-/formalin-induced nociception. Anti-inflammatory effects were assessed by zymosan A-induced peritonitis analysis. Antinociceptive and anti-inflammatory activities have also been reported for a sulfated polysaccharide fraction from Gracilaria caudate ( Chaves et al., 2013), a galactan from Gelidium crinale ( de Sousa et al., 2011), a mucin-binding agglutinin from Hypnea cervicornis (Bitencourt et al., 2008), and a lectin from Pterocladiella capillacea (Silva et al., 2010) .
More recent research on extracts of red marine algae suggest that specific carbohydrates (sulfated polysaccharides) may inhibit both the DNA and RNA of viral infections and may operate both outside and within our infected cells (Baba et al., 1988, Mitsuya et al., 1988, Ueno and Kuno, 1987.) Work done in this area has shown that sulfated polysaccharide compounds suppressed retroviral replication and inhibited viral reverse transcriptases (Solomon et al., 1966, Schaffrath et al., 1976). A study done by Neushul (1990) showed that nearly all 39 species of marine red algae, including the family Halymeniaceae, also contained and exhibited an inhibitory substance that suppressed retroviral replication and inhibited viral reverse transcriptases. Studies by Nakashima et al., (1987, 1988) support the hypothesis that a common immunomodulatory cell wall carbohydrate, like carrageenan, is a type of heparin receptor molecule, binding to a cell and triggering a specific cellular response sequence. Carrageenan may also be internalized into infected cells, thus inhibiting the virus. It also may inhibit fusion between infected cells Neushul (1990), Gonzales et al., (1987) suggesting that sulfated polysaccharides inhibit a step in viral replication subsequent to viral internalization but prior to the onset of late viral protein synthesis.

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CHAPTER 1
CHAPTER 2
2.1 THE HUMAN IMMUNODEFICIENCY VIRUS (HIV).
2.2 CANCER
2.3. NATURAL PRODUCTS AS SOURCE OF BIOLOGICALLY ACTIVE COMPOUNDS.
2.4 MARINE ORGANISMS AS NATURAL SOURCE FOR BIOACTIVE COMPOUNDS
2.5. SCREENING TECHNIQUE OF MARINE ORGANISMS
2.6. RED SEA ECOSYSTEM
2.7. STRATEGIES FOR THE DISCOVERY OF MARINE DRUGS
2.8. THE ROLE OF LIPOPHILICITY IN DRUG DEVELOPMENT
2.9. COMMON DRUG DISCOVERY TECHNIQUES
2.10. Analytical techniques
2.11. HYPOTHESIS
2.12. PURPOSE AND OBJECTIVE OF THE STUDY
2.13. SCREENING STRATEGY
2.14. OUTPUTS
CHAPTER 3
3.1. BACKGROUND
3.2. METHODS
3.3. RESULTS AND DISCUSSION
3.4. CONCLUSION
3.5. AUTHORS‘ CONTRIBUTIONS
CHAPTER 4
4.1. INTRODUCTION
4.2. EXPERIMENTAL SECTION
4.4. CONCLUSIONS   ACKNOWLEDGMENTS
CHAPTER 5
5.1. INTRODUCTION
5.2. AREA OF THE STUDY
5.3. METHODS
5.4. RESULTS
5.5. DISCUSSION
5.6. CONCLUSIONS
CHAPTER 6
6.1. OVERVIEW
6.2. CHAPTER 3. THE RANDOM SCREENING OF MARINE ORGANISMS
6.3. CHAPTER 4. ISOLATION AND BIOLOGICAL EVALUATION L. ARBOREUM METABOLITES:
6.4. CHAPTER 5: SEASONAL EVALUATION OF THE ACTIVE TRITERPENE ISOLATED FROM L. ARBOREUM AND ITS ECOLOGICAL CONSEQUENCES.
6.5. REVISITING HYPOTHESIS
6.6. HYPOTHESIS ACCEPTED
6.7. FUTURE WORK
6.8. OTHER INVESTIGATIONS
6.9. CONCLUSION
APPENDIX
8.1. ADDITIONAL INFORMATION FOR CHAPTER 3
8.2. ADDITIONAL INFORMATION FOR CHAPTER 4
8.3. ADDITIONAL INFORMATION FOR CHAPTER 5
GLOSSARY

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