Chemical and Biological Evaluation of Bioactive Secondary Metabolites Isolated from Endophytic Fungi of Hedera helix L. Plant / By Sarah Mohamed Osama Saeed; supervisor Prof. Dr. Moshera M. El-Sherei Professor of Pharmacognosy Faculty of Pharmacy Cairo University, Prof. Dr. Osama M. Salama Late Professor of Pharmacognosy Vice President Future University in Egypt, Prof. Dr. Osama M. Salama Late Professor of Pharmacognosy Vice President Future University in Egypt, Assoc. Prof. Marwa M. Rafaat Associate Professor of Microbiology Faculty of Pharmacy Future University in Egypt, Dr. Mokhtar M. Bishr Technical Director, Plant Manager of Arab Co. For Pharmaceuticals & Medicinal Plants (Mepaco).

Under the Supervision of Prof. Dr. Moshera M. El-Sherei Professor of harmacognosy Faculty of Pharmacy Cairo University Prof. Dr. Osama M. Salama Late Professor of Pharmacognosy Vice President Future University in Egypt Prof. Dr. Dalia A. M. Al-Mahdy Professor of Pharmacognosy Faculty of Pharmacy Cairo University Pharmacognosy Department Faculty of Pharmacy Cairo University Egypt 2024 Assoc. Prof. Marwa M. Rafaat Associate Professor of Microbiology Faculty of Pharmacy Future University in Egypt Dr. Mokhtar M. Bishr Technical Director, Plant Manager of Arab Co. For Pharmaceuticals & Medicinal Plants (Mepaco)

For the Degree of Doctor of Philosophy in Pharmaceutical Sciences (Pharmacognosy).

Master Degree of Pharmacognosy - Faculty of Pharmacy- Cairo University 2019.

Includes bibliographical references.

The demand for new and useful compounds to help and relieve people in
all aspects of their lives is constantly increasing. Drug resistance in bacteria, the
emergence of life-threating viruses, the enormous spreading of cancer, recurring
disease problems in organ transplant recipients, and the massive increase in the
incidence of fungal infections in the world's population all highlight our inability
to deal with those medical issues. Owing to all these facts, there is a need to
explore new and useful bioactive compounds to provide assistance and relief in
all aspects of human conditions. Thus, the aim of this study was to screen the
well-known medicinal plant Hedera helix L. for its endophytic fungi and to
investigate their potential antimicrobial activities as well as their L-asparaginase
production ability. Bio-guided fractionation approach was conducted to isolate
the pure compounds from the most active fungal fraction. Out of total 6 different
isolated endophytic fungal strains, only Aspergillus cejpii showed the highest
activity against all tested microbial strains. The bio-guided fractionation of the
DCM: MeOH fraction led to the isolation of spiculisporic acid. The compound
showed good antimicrobial activities with minimum inhibitory concentration
(MIC) values ranging from 3.9-31.25 μg/mL against all tested strains.
Concerning the L-asparaginase enzyme production, Fusarium solani
showed highest L-ASNase production (22.76 IU/ml/hr) and thus was selected for
additional characterization and optimization studies on maximizing its
productivity in addition to evaluating its subsequent cytotoxicity towards acute
monocytic leukemia (THP1) and Human Skin Fibroblast (HSF) cell lines where
it revealed promising cytotoxic activity against acute monocytic leukemia with
IC50 = 3.66 μg/ml with low cytotoxicity against tested normal Human Skin
Fibroblast cell line.

Text in English, abstracts in English and Arabic.