الفهرس 
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Abstract
Marine microorganisms, especially fungi have a crucial impact in the pharmaceutical as well as the agricultural industries as a result of their tendency to produce a large array of natural products with a unique diversity of chemical structure that proves their potential for specific medicinal and agrochemical applications. Furthermore, most of those fungal-derived secondary metabolites show biological activities in pharmaceutically relevant bioassays which furnish potential lead candidates that could be optimized to yield effective therapeutic and bioactive agents.
The aim of this dissertation was the investigation of natural products from fungi isolated out from marine sources. Three marine-derived, coral-derived, fungal strains, Scopulariopsis Sp., Alternaria sp. and Gliomastix sp. were selected as biological sources. The fungi were grown mainly on solid rice medium as well as, in some cases, solid beans medium for a period of four to six weeks. Chemical investigations of the obtained extracts were then carried out through different chromatographic separation techniques in order to isolate the secondary metabolites. Moreover, structure elucidation was performed using different spectroscopic techniques, including mass spectrometry (MS) and nuclear magnetic resonance (NMR) experiments. The stereochemistry of chiral compounds was determined by comparison of their optical rotation with the literature or by ECD calculations. Finally, the isolated compounds were subjected to bioactivity assays, including antibacterial and cytotoxicity assays.
Furthermore, in order to activate silent biosynthetic gene clusters, different methods were employed to culture selected fungal strains. Fermentation on different culture media as well as co-cultivation with bacteria successfully induced the production of some secondary metabolites that were not isolated from the axenic culture.
1. Scopulariopsis sp.
Scopulariopsis sp. was isolated from Red Sea hard coral, Stylophora sp. Twenty-nine compounds were isolated when the fungus cultured on solid rice medium. These compounds belong to xanthones, sesquiterpenes, alkaloids and polyketides. Six compounds were identified as new natural products.
The first approach to trigger silent biosynthetic gene clusters was performed through cultivation of Scopulariopsis sp. in different media other than rice medium, resulted in the accumulation of a different nineteen natural products on fermentation of the same strain on solid beans medium compared to the rice culture.
Meanwhile, the second approach was carried out through co-cultivation with the bacteria S. lividans or B. subtilis on solid rice containing YM media resulted in the production of an additional metabolite, alternariol (49), when cultivated with S. lividans that was not found compared to the axenic cultures of Scopulariopsis sp. However, co-cultivation with B. subtilis failed to induce changes in fungal natural product accumulation in contrast to co-cultures with Streptomyces sp.
2. Alternaria sp.
Fifteen known compounds were isolated from the fungus Alternaria sp., which was isolated from the Red Sea hard coral, Stylophora sp. when cultivated on solid rice medium.
3. Gliomastix sp.
Fifteen compounds were isolated from the solid rice cultures of Gliomastix sp. that was isolated from the Red Sea hard coral, Stylophora sp. These compounds mainly include hydroquinone and hydroquinone glycosides as well as one sulfur-containing alkaloid. Eight compounds of which were identified as new natural products. One of the new hydroquinone derivatives, gliomastin A (64) showed a potent cytotoxic activity against different cell lines while gliomastin C (66) exhibited a selective antitubercular activity.
Co-cultivation of Gliomastix sp. with S. lividans or B. subtilis on solid rice containing YM media resulted in the production of an additional metabolites as well as suppression of some of the major metabolites observed in the axenic rice culture when cultivated with S. lividans on comparison to the axenic culture. However, co-cultivation with B. subtilis failed to induce changes in fungal natural product production.
In conclusion, a total of seventy-eight compounds were isolated and identified from three different marine-derived fungal strains, in which, eighteen were identified as new natural products. Both known and new compounds were tested for their biological activities using different bioassay systems. Different culture approaches successfully triggered the accumulation of distinct metabolites compared to axenic controls.
Furthermore, two of the major fungal metabolites isolated here in this work were also obtained from the host coral crude extract through analysis of this extract, which illustrated the possible relationship existing between the host organism, Red Sea hard coral Stylophora sp., and the isolated fungal strains.