الفهرس 
Introduction
Chapter I : Isolation of compounds from Clonostachys roseaOnly 14 pages are availabe for public view
 |  | from | 258 |  |  |
| | | from | 258 | | |
Abstract
Since the discovery of penicillin G, fungi have been considered as promising sources for drug discovery. One of the main advantages of exploring fungi for production of bioactive secondary metabolites is the huge diversity in the sources of fungi, for example soil-derived fungi, marine-derived fungi and plant endophytic fungi. However, the rediscovery rate of known compounds from fungi is a serious problem facing natural product chemistry as gene clusters responsible for biosynthesis of secondary metabolites often remain silent under laboratory culture conditions. Thus, only a fraction of fungal metabolites compared to its genetic potential can usually be detected in the extracts. To overcome this, OSMAC (One Strain Many Compounds) approach was adopted by altering the culture media in an attempt to activate the silent biosynthetic gene clusters present in this fungus. In addition, co-culture strategies are another approach aiming at an induction of silent biogenetic gene clusters through mimicking the natural microbial ecosystem where there is competition for nutrients with other microorganisms.
In the present study, fungi from each of the aforementioned sources were studied. The soil-derived fungal strain Clonostachys rosea, the sponge-associated fungal strain Aspergillus versicolor and the endophytic fungi Ulocladium chartarum and Ulocladium botrytis. OSMAC approach was applied on Clonostachys rosea by cultivation of different media. Co-culture technique was implemented with Aspergillus versicolor through co-culture with Bacillus subtilis.
Part I
Isolation and structure elucidation of secondary metabolites of different cultures of Clonostachys rosea
Chapter I: Isolation of compounds from Clonostachys rosea
Chapter II: Structure elucidation of compounds isolated from Clonostachys rosea
Part II
Isolation and structure elucidation of secondary metabolites of the marine-derived fungus Aspergillus versicolor co-cultivated with Bacillus subtilis
Chapter I: Isolation of secondary metabolites of the marine-derived fungus Aspergillus versicolor co-cultivated with Bacillus subtilis
Chapter II: Structure elucidation of compounds isolated from Aspergillus versicolor co-cultivated with Bacillus subtilis
Part III
Biological and microbiological studies
Chapter I: Biological activties of the isolated compounds
Compounds isolated from Clonostachys rosea
Compounds isolated from Aspergillus versicolor
Chapter II: Evaluation of biological activities of different extracts of the fungi
Ulocladium chartarum and Ulocladium botrytis
1-Ulocladium chartarum total phenol content and antioxidant activity
2-Ulocladium botrytis total phenol content and antioxidant activity
3-Antimicrobial activity of different extracts of Ulocladium chartarum and Ulocladium botrytis
4-Antileishmanial activity of different extracts of Ulocladium chartarum and Ulocladium botrytis
5-Anti-trypanosomal activity of different extracts of Ulocladium chartarum and Ulocladium botrytis
6-Antimalarial activity of different extracts of Ulocladium chartarum and Ulocladium botrytis
Part I
Isolation and structure elucidation of secondary metabolites of different cultures of Clonostachys rosea
Chapter I: Isolation of compounds from Clonostachys rosea
The soil derived fungal strain Clonostachys rosea isolated from a soil sample from Indonesia was cultivated on rice medium (axenic culture) and the crude EtOAc extract was phytochemically investigated. The extract was subjected to liquid-liquid fractionation followed by various chromatographic techniques; VLC, Sephadex LH-20 and finally semi-preparative HPLC purification. Five compounds have been isolated from the axenic culture.
Changing the culture medium into beans, as an application of OSMAC approach, led to the isolation of three compounds by various chromatographic techniques.
Chapter II: Structure elucidation of compounds isolated from Clonostachys rosea
Structures of the isolated compounds from different cultures of Clonostachys rosea (Compounds 1-8) were elucidated on the basis of 1D, 2D-NMR spectral data and HRESIMS together with comparison with the available literature. Five new compounds (compounds 1-3, 4, 8) in addition to three known compounds (5-7). Compounds (1-3) were proved to be three new cyclic peptides, compound (4) was a new γ-lactam derivative and compound (8) is a new furanone derivative.
Part II
Isolation and structure elucidation of secondary metabolites of the marine-derived fungus Aspergillus versicolor co-cultivated with Bacillus subtilis
Chapter I: Isolation of secondary metabolites of the marine-derived fungus Aspergillus versicolor co-cultivated with Bacillus subtilis
The crude EtOAc extract of the co-culture was fractionated by vacuum liquid chromatography to yield to yield 19 fractions. Different chromatographic separation techniques, (smaller VLC columns, Sephadex LH-20 and semipreparative HPLC) were applied on the promising fractions leading to the isolation of twenty four compounds.
Chapter II: Structure elucidation of compounds isolated from Aspergillus versicolor co-cultivated with Bacillus subtilis
Structures of the isolated compounds from the co-culture (Compounds 9-32) were elucidated on the basis of 1D, 2D NMR spectral data and HRESIMS in addition to comparison with the available literature. Three new compounds were identified, a new cyclic pentapeptide, cotteslosin C (10), a new aflaquinolone, 22-epi-aflaquinolone B (11), and a new anthraquinone, isoversicolorin B (16) together with 21 known compounds. It is noteworthy that the new metabolites were only detected in the co-culture extract but not when the fungus was grown under axenic conditions.