In this study isolates from Thymelaea hirsuta, a wild plant from the Sinai Peninsula of Egypt, were identified and their selective cytotoxicity levels were evaluated. Phytochemical examination of the ethyl acetate (EtOAc) fraction of the methanolic (MeOH) extract of the plant led to the isolation of a new triflavanone compound (1), in addition to the isolation of nine previously reported compounds. These included five dicoumarinyl ethers found in Thymelaea: daphnoretin methyl ether (2), rutamontine (3), neodaphnoretin (4), acetyldaphnoretin (5), and edgeworthin (6); two flavonoids: genkwanin (7) and trans-tiliroside (8); p-hydroxy benzoic acid (9) and β sitosterol glucoside (10). Eight of the isolated compounds were tested for in vitro cytotoxicity against Vero and HepG2 cell lines using a sulforhodamine-B (SRB) assay. Compounds 1, 2 and 5 exhibited remarkable cytotoxic activities against HepG2 cells, with IC50 values of 8.6, 12.3 and 9.4 μM, respectively, yet these compounds exhibited non-toxic activities against the Vero cells. Additionally, compound 1 further exhibited promising cytotoxic activity against both MCF-7 and HCT-116 cells, with IC50 values of 4.26 and 9.6 μM, respectively. Compound 1 significantly stimulated apoptotic breast cancer cell death, resulting in a 14.97-fold increase and arresting 40.57% of the cell population at the Pre-G1 stage of the cell cycle. 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 towards Ras activation/pathway mitogen-activated protein kinase (Ras/MAPK); a common molecular pathway in the development and progression of liver tumors.
Truthfully, natural products have been the principal productive source of advancing new drugs. The broad aim of this work was to conduct a phytochemical and biological study of the Red Sea soft coral Sarcophyton glaucum, Family: Alcyoniidae collected from Red Sea at the Egyptian coasts. The phytochemical investigation from the soft coral S. glaucum led to the isolation of ten compounds including: palmitic acid (1), stearic acid (2), (24S)-24-methyl cholesterol (3), batyl alcohol (4), heptadecanoic acid pentadecyl ester (5), sarcophine ( 6), (+)-7α, 8βdihydroxydeepoxysarcophine (7), uracil (8), thymine (9) and a ceramide (10). As cancer is one of the most hazardous factors threatening the human life, in this study the potential in-vitro cytotoxicity of the soft coral S. glaucum extract and three marine isolates were measured against HepG2 and MCF7 using Sulphorhodamine-B (SRB) assay and all of the tested samples showed a good cytotoxic activities against both hepatic and breast cancer. The extract of S. glaucum was tested also against the protozoan parasite Leishmania donovani, using pentamidine and amphotericin B as controls and showed antileishmanial activity.
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