الفهرس | Only 14 pages are availabe for public view |
Abstract Truly, natural products have been the foremost fruitful source of advancing new drugs. The broad aim of this thesis was to conduct a phytochemical and biological study of the plant Thymelaea hirsuta, Family: Thymelaeaceae as well as the Red Sea soft coral Sarcophytonglaucum, Family: Alcyoniidae collected from Red Sea at the Egyptian coasts. The phytochemical investigation of T. hirsura led to the isolation of a new triflavanone compound (10) in addition to nine previously reported compounds. These include five dicoumarinyl ethers first reported from Thymelaea: daphnoretin methyl ether (3), rutamontine (4), neodaphnoretin (5), acetyldaphnoretin (6), and edgeworthin (7); two flavonoids: genkwanin (2) and trans tiliroside (9); p-hydroxy benzoic acid (1) and β sitosterol glucoside (8), in addition to the isolation of ten compounds from the soft coral S. glaucum including: palmitic acid (11), stearic acid (12), (24S)-24-methyl cholesterol (13), batyl alcohol (14), heptadecanoic acid pentadecyl ester (15), sarcophine(16), (+)-7α, 8β-dihydroxydeepoxysarcophine (17), uracil (18), thymine (19) and a ceramide (20). As cancer is one of the most dangerous factors threatening the human health, in this study in-vitrocytotoxicity of eight of the isolates of T. hirsuta was tested against Vero and HepG2 cell lines using Sulphorhodamine-B (SRB) assay. Compounds 3,6and10exhibited remarkable cytotoxic activities against HepG2 cells with IC50 values of 12.3,9.4 and 8.6μM, they exhibited non-toxic activities against the Vero cells. Additionally, compound 10 further exhibited promising cytotoxic activity against both MCF-7 and HCT-116 cells with IC50 values of 4.26 and 9.6 μM using MTT assay. Compound 10 significantly stimulated apoptotic breast cancer cell death with 14.97-fold arresting the cell cycle at Pre-G1 with 40.57% population. Finally, its apoptosis-inducing activity was further validated through activation of BAX and Caspase-9 and inhibition of BCL2 levels. In-silico molecular docking experiments revealed a good binding mode profile of the isolates toward Ras activation/Pathway mitogen-activated protein kinase (MAPK), a common molecular pathway in the development and progression of liver tumors. The potential in-vitrocytotoxicity of the soft coral S.glaucumextract and three marine isolates were measured against HepG2 and MCF7 and all of the tested samples showed a good anticancer activity against both hepatic and breast cancer. Chemical profiling of extract of T. hirsuta was achieved by LC-ESI-TOF-MS/MS analysis. Thirty -eight hits mainly phenolics were detected. The unfolding of the global COVID-19 pandemic and the lack of specific treatment call for use of all sources to find a treatment for this scourge. In the prevailing study, the use of molecular docking, we perceive new probably inhibitors of (SARS-CoV-2) through compounds isolated from T. hirsuta and also among metabolomics. The extract ofS. glaucum was tested also against the protozoan parasite Leishmania donovani, using pentamidine and amphotericin B as controls, indicated that this marine has antileishmanial activity. |