الفهرس 
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Abstract
Urospermum picroides was collected and identified from different areas El-Omayed Biosphere Reserve area in North coast, Alexandria, Egypt. Two endophytic fungi were isolated, identified and designated as F.oxysporum (DF) and P.herbarum (DP) according to the results of molecular identification based on phylogenetic tree analysis according to DNA sequence data and NCBI. After measuring optimization parameters for both endophytic fungi (DF and DP), it was found that PDA medium, dextrose as carbon source, pH 5.5 and 25 ºC were the optimum parameters for both isolated endophytic fungi. It was noticed that extracellular metabolites (EMDF and EMDP) have the most antimicrobial activity compared to intracellular metabolites of both DF and DP endophytic fungi. Results showed high antimicrobial activities of extracellular metabolites of DF (EMDF) with MIC (350μg/ml) against S.aureus, B.cereus, C.tropicalis and T.mentagrophytes. Also, for (EMDP) MIC (350μg/ml) was found against S.aureus, Salmonella sp, C.tropicalis, C.albicans and T.mentagrophytes. Electron microscope was used to investigate the mechanism of action of the most effective extracts of EMDP on B.cereus and C.albicans and of EMDF on Trichophyton mentagrophytes. In C.albicans, the cells had undergone distinct morphological and cytological alternations and appeared shrinked compared with un treated cells. Also, B.cereus treated cells appeared to be shrinked, degradation of cell walls and the cells were depressed from the middle. Moreover, several changes in hyphae of treated Trichophyton mentagrophytes it appeared shrinked with rough surface, a flat ribbon – shaped structure with demolition of cell wall, cell wall thickening and disordered hyphal tip. Evaluation of medicinal properties was done for EMDF and EMDP by measuring their antioxidant and antitumor activities. These extracts showed high antioxidant activities (24.5% and 51.7%), respectively. Also, this is the first study to investigate the antitumor activity of EADF and EADP against human liver cancer cell line which then confirmed by upregulation of p53, BaX (2.14 and 2.2), respectively and down regulation of Bcl2 (0.16) using quantitative reverse transcriptase polymerase chain reaction technique (RT-qPCR). Finally, identification of active metabolites of these two extracts (EMDF and EMDP) were done by using GC-MS spectroscopy which revealed that the most active compound was Diisooctyl phthalate in (EMDF) and Benzoic acid, 3, 5-bis (1, 1-dimethylethyl)-4-hydroxy-methyl ester in (EMDP). These compounds may play an important role in antimicrobial, antioxidant and antitumor activities of (EMDF) and (EMDP).