الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
The oceans cover over 70% of the earth’s surface and contain over 300,000 described species of plants and animals. The ocean is also the source of structurally unique natural products with diverse pharmacological activities. Sponges are aquatic animals that occur in all oceans and also in fresh water and have a wide distribution from tropical to temperate to arctic regions. Recently sponges and sponge-associated microorganisms become a valuable sources for structurally unique metabolites with anti-inflammatory, antitumor, immunosuppressive or neurosuppressive, antiviral, antimalarial, antibiotic, or anti-biofilm activities.
The present study included three parts:
Part one (Phytochemical and Biological Screening of Callyspongia siphonella Levi, 1965 Collected from the Red Sea):
In this part, chemical investigation of secondary metabolites produced by the Red sea sponge Callyspongia siphonella (Levi, 1965) furnished two brominated oxindole alkaloids (1, 2) from a natural source for the first time, two sipholane triterpenes (3, 4), five steroidal compounds (5-9) and the fatty acid petroselenic acid (10). Furthermore, the fatty acids content of the sponge was characterized by GC-MS for the first time. Compound 1 and 2 showed antibacterial activity against gram-positive bacteria Staphylococcus aureus and Bacillus subtilis (MIC = 32 and 16 µg/mL), (MIC = 64 and 16 µg/mL), respectively. Also they displayed moderate anti-biofilm activity in Pseudomonas aeruginosa PA01 (49.32% and 41.76% inhibition, respectively).
Part two (Production of induced bioactive phenolic metabolites in the Callyspongia siphonella derived fungus Penicillium brevicompactum using epigenetic modifiers):
In this part we found that treatment of the marine derived fungus P. brevicompactum with HDACs inhibitors (nicotinamide and sodium butyrate) resulted in induction of phenolic metabolites production. Fungal extracts obtained from these treatments and mainly from nicotinamide treatment, exhibited antioxidant and antibacterial activities. Processing of nicotinamide treatment led to isolation of nine (1-9) phenolic compounds, however, sodium butyrate treatment led to the isolation of two compounds (10, 11). Compounds 1 and 2 showed the highest antibacterial activity against tested Gram-positive bacteria. On the other hand, compounds 4 and 5 showed the highest antibacterial activity against tested Gram-negative bacteria. In addition, compounds (4-6) exhibited potent in vitro free radical scavenging, and antiproliferative activities. A pharmacophore model was carried out using compounds 4-6, validation of this model was shown through testing the antioxidant activity of gallic acid and compares it with the prediction power of the model. Testing of the compounds 1-11, as well as gallic acid for their antiproliferative activities against HepG2 cancer cell line showed that, compounds 4-6 which exhibited the highest antioxidant activity in DPPH assay are also active as antiproliferative agents. Consequently, these findings suggest similar mechanism of action of these compounds. This study showed that nicotinamide treatment is a potential tool for the induction of cryptic genes for bioactive phenolic secondary metabolites production in fungi. Additionally, each HDACs inhibitor affected the fungal biosynthetic machinery in different ways.
Part three (Production of induced bioactive secondary metabolites by co-cultivation of sponge-associated actinomycetes, Saccharomonospora sp. UR22 and Dietzia sp. UR66):
In this part of our work, we report on another example of the induction of two new bioactive secondary metabolites 22 and 23 along with other three known metabolites 24-26 in response to microbial co-cultivation of two marine actinomycetes, Saccharomonospora sp. UR22 and Dietzia sp. UR66, derived from the Red sea sponge Callyspongia siphonella. The HPLC and TLC chromatograms of the two monocultures together with the co-culture derived extracts showed that compounds 22-26 were produced only during the co-fermentation of both microbes. On the other hand, axenic culture of Saccharomonospora sp. UR22 led to isolation of a set of known microbial metabolites (27-32). Compounds 22 and 24 exhibited potent antiproliferative activities towards HL-60 and HT-29. Based on previous reports on similar compounds and docking study in the ATP-binding site of Pim-1 kinase and the in-vitro Pim-1 kinase assay results we suggested that both compounds 22 and 24 mediated their cytotoxicity by inhibiting the well-known oncoprotein Pim-1 kinase. These findings highlighted the co-cultivation approach as an effective strategy to enhance the chemical diversity of the secondary metabolites hidden in the genomes of the marine actinomycetes.