الفهرس 
AcknowledgmentOnly 14 pages are availabe for public view
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Abstract
Natural products play a highly significant role in drug discovery, which has been reviewed recently. The oceans, which is called ”the mother origin of life” cover over 70% of the earth’s surface and contain over 300,000 described species of plants and animals. The oceans have been the source of structurally unique natural products with diverse pharmacological activities. The diversity in species is extraordinarily rich on coral reefs, where there are around 1,000 species per m2 in some areas, and the Indo-Pacific Ocean has the world’s greatest tropical marine biodiversity.
Part I: Chemical and Biological Investigation of the marine sponge Phyllospongia lamellosa collected from the Red Sea Hurghada, Egypt. Sponges are the largest source of new marine natural products reported annually and they have been providing a vast of bioactive compounds for the pharmaceutical industry since the 1950s. Sponges are well represented in the marine environment, with over 7000 species described, ranging from shallow-water to those inhabiting depths of over 8000 m, with some deep-water species. So our study concerned with isolation of active metabolites from Phyllospongia lamellosa.
Chapter I: Chemical Investigation
Chemical investigation of the dichloromethane fraction using column chromatography and preparative HPLC afforded; five new scalarane sesterterpenes named ; phyllospongins A–E (1-3 and 7-8), besides four known derivatives isolated for the first time from this genus, 12α-acetoxy-20,24-dimethyl-25-norscalar-16-en-24-one (4), 12α-acetoxy-24,25-epoxy-24-hydroxy-20,24-dimethylscalarane (5) and scalardysin-A (6), 12α-acetoxy-13β,18β-cyclobutan-20,24-dimethyl-24-oxoscalar-16-en-25β-ol (9). The structures of the isolated compounds were identified using different spectroscopic techniques 1D and 2D.
GC/MS analysis for fatty acids constituents was carried out on n-hexane fraction. Pentadecanoic acid, 14-methyl, methyl ester was the major saturated fatty acids constituents in Phyllospongia lamellosa 18.39%. As well, 9-Hexadecenoic acid, methyl ester was the major unsaturated fatty acid 11.59%.
Chapter II: Biological studies
Screening for the isolated compounds cytotoxic activities against human breast cancer cell line (MCF-7), human colon cancer cell line (HCT-116) and human liver cancer cell line (HePG-2). Results of cytotoxic screening revealed that compounds 2, 3, 6, 7 and 8 had potent cytotoxic activity against HCT-116 with compound 7 as potent as doxorubicin while 8 showed cytotoxic activity against MCF-7 comparable to Doxorubicin.
Antibacterial screening was evaluated against the Gram-positive strains Staphylococcus aureus ATCC25923, and Bacillus subtilis NCTC2116 and the Gram-negative strains Escherichia coli ATCC25922 and Vibrio parahemolyticus NCTC10441, using the agar diffusion method. Results of antibacterial screening showed that all the compounds had inhibitory activity against Gram-positive strains with compounds 7, 8 and 9 showing the most potent activity (~ 1.7-3.3 μg/ml) in comparison with the other compounds which showed weak activity.
Part II: Chemical and Biological Investigation of the Soft Corals Lobophytum pauciflorum collected from the Red Sea, Hurghada, Egypt. Soft corals are found worldwide, more in tropical than temperate reefs, mainly in middepths of 5-30 meters, temperature varied from 24- 35oC and pH 8.2- 8.4. Soft corals of the genus Lobophytum, a marine invertebrate of the subclass Alcyonaria, are rich source of diterpenes, lipids, sesquiterpenes and hydroxylated steroids. Cembrane diterpenes previously isolated from Lobophytum species; have shown diverse biological activities as cytotoxic, antiarthritic, anti-inflammatory and antibacterial. Previous works encourage us to collect the marine soft coral Lobophytum pauciflorum from the Red Sea, Hurghada, Egypt for phytochemical and biological screening.
Chapter I: Chemical Investigation
Chemical investigation of using chromatographic separation and purification through silica gel for column and sephadex LH-20 with n-hexane, ethyl acetate and methanol; yielded six known metabolites; heptadecan-1-ol, nephthenol, gorgost-5-en-3β-ol, palmitic acid, Stearic acid and Batilol (10-15).
GC/MS analysis for fatty acids constituents was carried out on n-hexane fraction. Hexadecanoic acid, methyl ester was the major saturated fatty acids constituent 25.01%. As well, 7,10-Hexadecadienoic acid, methyl ester was the major unsaturated fatty acid of 5.38%.
GC/MS analysis of Lobophytum pauciflorum fatty acid constituents confirmed the presence of the isolated compounds [palmetic acid (13) and stearic acid (14)].
Chapter II: Biological Studies
Antimicrobial screening was evaluated against Gram +ve (Bacillus subtilis, Streptococcus faecalis, Staphyllococcus aureus) and Gram –ve (Escherichia coli, Neisseria gonorrhoeae, Pseudomonas aeruginosa) using disc agar diffusion method. The Results showed that n-hexane and ethyl acetate showed remarkable inhibitory activity against Bacillus subtilis compared with Tetracycline also ethyl acetate showed remarkable inhibitory activity against Staphyllococcus aureus. Testing MIC for the isolated compounds resulted in inhibitory activity for micro-organisms ranging from 50 µg/ml to 25 µg/ml with compounds (10, 11, 12-15).
In vitro anti-inflammatory screening for different fractions showed that n-hexane, dichloromethane fractions showed significant anti-inflammatory activity against COX-1 and COX-2 in addition to ethyl acetate fraction compared with Indomethacin and Celecoxib. As well, compounds (11 and 12) showed significant anti-inflammatory activity against COX-1 and COX-2 compared with Indomethacin and Celecoxib.
Part III: Isolation, Chemical Profiling of Marine derived microorganisms and Biological Screening.
Microorganisms, and in particular the bacteria, showed a deep effect on developing chemistry and medical science. Since the discovery of penicillin in 1929, extensive studies of mainly soil derived bacteria and fungi revealed that microorganisms are a rich source of structurally-unique, bioactive substances.
Chapter I: Microbial Isolation and Chemical Investigation
Isolation and purification of microorganisms from different marine samples collected from the Red Sea, Hurghada, Egypt using different agar media resulted in isolation of pure seven microorganisms. Preparation of different extracts for antimicrobial screening.
Chemical profiling for microorganisms extracts using LC-HRESIMS Analysis. Chemical profiling results recommend large scale fermentation more than 40 L for Cladiella sp. and Phyllospongia lamellosa derived microorganisms to isolate and identify the remarkable hits that may lead to isolation of new derivative or new lead compounds. These constituents may provide the scientific evidences for antimicrobial activities of the microorganisms extracts.
NMR analysis of the ethyl acetate extract of Phyllospongia lamellosa derived microorganisms resulted in identification of the phthalate derivative Di-(2-ethylhexyl) phthalate.
Chapter II: Biological Studies
Antibacterial screening was carried out on the ethyl acetate and methanol extracts using agar diffusion method. The results showed varied inhibitory activity against Gram +ve (Bacillus subtilis and Staphyllococcus aureus), Gram –ve (Escherichia coli) and fungi (Candida albicans). Phyllospongia derived microorganisms (12O) ethyl acetate extract showed remarkable inhibitory activity against both Gram +ve and Gram –ve bacteria with no effect on fungi while (12Y) extracts showed antifungal activity. Cladiella derived micro-organisms (8Y) ethyl acetate extract showed only inhibitory activity against Gram +ve bacteria while Black sponge derived microorganism (3Y) showed antifungal against Candida albicans.