Abdelhameed RFA et al. (2020), New Cytotoxic Cerebrosides from the Red Sea Cuc...

ECB-ART-49698

Mar Drugs 2020 Aug 01;188:. doi: 10.3390/md18080405.

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New Cytotoxic Cerebrosides from the Red Sea Cucumber Holothuria spinifera Supported by In-Silico Studies.

Abdelhameed RFA , Eltamany EE , Hal DM , Ibrahim AK , AboulMagd AM , Al-Warhi T , Youssif KA , Abd El-Kader AM , Hassanean HA , Fayez S , Bringmann G , Ahmed SA , Abdelmohsen UR .

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Bioactivity-guided fractionation of a methanolic extract of the Red Sea cucumber Holothuria spinifera and LC-HRESIMS-assisted dereplication resulted in the isolation of four compounds, three new cerebrosides, spiniferosides A (1), B (2), and C (3), and cholesterol sulfate (4). The chemical structures of the isolated compounds were established on the basis of their 1D NMR and HRMS spectral data. Metabolic profiling of the H. spinifera extract indicated the presence of diverse secondary metabolites, mostly hydroxy fatty acids, diterpenes, triterpenes, and cerebrosides. The isolated compounds were tested for their in vitro cytotoxicities against the breast adenocarcinoma MCF-7 cell line. Compounds 1, 2, 3, and 4 displayed promising cytotoxic activities against MCF-7 cells, with IC50 values of 13.83, 8.13, 8.27, and 35.56 µM, respectively, compared to that of the standard drug doxorubicin (IC50 8.64 µM). Additionally, docking studies were performed for compounds 1, 2, 3, and 4 to elucidate their binding interactions with the active site of the SET protein, an inhibitor of protein phosphatase 2A (PP2A), which could explain their cytotoxic activity. This study highlights the important role of these metabolites in the defense mechanism of the sea cucumber against fouling organisms and the potential uses of these active molecules in the design of new anticancer agents.

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References [+] :

Abdelhameed, New Cytotoxic Natural Products from the Red Sea Sponge Stylissa carteri. 2020, Pubmed

	Figure 1. Chemical structures of spiniferoside A1âA3.
	Figure 2. Chemical structure of the newly discovered compound 2, spiniferoside B.
	Figure 3. Chemical structure of compound 3, spiniferoside C.
	Figure 4. Chemical structure of compound 4, cholesterol-3-O-sulfate.
	Figure 5. Dereplicated metabolites from Holothuria spinifera.
	Figure 6. Crystal structure of the predicted docking pose (in blue) of (A) compound 2 and (B) compound 3 with the SET oncoprotein (PDB code: 2E50).