Abdelhafez, Omnia HeshamFahim, John RefaatEl Masri, Ramy RSalem, M. AlarabyDesoukey, Samar YehiaAhmed, SafwatKamel, Mohamed SalahPimentel-Elardo, Sheila MarieNodwell, Justin RAbdelmohsen, Usama Ramadan2021-07-172021-07-172021-06https://doi.org/10.1039/d1ra03045khttp://repository.msa.edu.eg/xmlui/handle/123456789/4621Soft corals belonging to the family Nephtheidae have been appreciated as marine sources of diverse metabolites with promising anticancer potential. In view of that, the current work investigates the anti- proliferative potential of the crude extract, different fractions, and green synthesized silver nanoparticles (AgNPs) of the Red Sea soft coral, Nephthea sp. against a panel of tumor cell lines. The metabolic pool of the soft coral under study was also explored via an LC-HR-ESI-MS metabolomics approach, followed by molecular docking analysis of the characterized metabolites against the target proteins, EGFR, VEGFR, and HER2 (erbB2) that are known to be involved in cancer cell proliferation, growth, and survival. Overall, the n- butanol fraction of Nephthea sp. exhibited the highest inhibitory activities against MCF7 (breast cancer) and A549 (lung cancer) cell lines, with interesting IC50 values of 2.30 0.07 and 3.12 0.10 mg ml 1 , respectively, whereas the maximum growth inhibition of HL60 (leukemia) cells was recorded by the total extract (IC50 ¼ 2.78 0.09 mg ml 1 ). More interestingly, the anti-proliferative potential of the total soft coral extract was evidently improved when packaged in the form of biogenic AgNPs, particularly against A549 and MCF7 tumor cells, showing IC50 values of 0.72 0.06 and 9.32 0.57 mg ml 1 , respectively. On the other hand, metabolic profiling of Nephthea sp. resulted in the annotation of structurally diverse terpenoids, some of which displayed considerable binding affinities and molecular interactions with the studied target proteins, suggesting their possible contribution to the anti-proliferative properties of Nephthea sp. via inhibition of tyrosine kinases, especially the EGFR type. Taken together, the present findings highlighted the relevance of Nephthea sp. to future anticancer drug discovery and provided a base for further work on the green synthesis of a range of bioactive NPs from marine soft corals.en-USlunng cancersilver nanoparticlesArticlehttps://doi.org/10.1039/d1ra03045k