- New cytotoxic cerebrosides from the red sea cucumber Holothuria spinifera supported by in-silico studies
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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.
- Abdelhameed, Reda F.A.,Eltamany, Enas E.,Hal, Dina M.,Ibrahim, Amany K.,AboulMagd, Asmaa M.,Al-Warhi, Tarfah,Youssif, Khayrya A.,Abd El-Kader, Adel M.,Hassanean, Hashim A.,Fayez, Shaimaa,Bringmann, Gerhard,Ahmed, Safwat A.,Abdelmohsen, Usama Ramadan
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- Synthesis of (2S,3R,4E)-1-O-(β-D-Glucopyranosyl)-N--4-icosasphingenine, a New Esterified Cerebroside Isolated from Human and Pig Epidermis
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(2S,3R,4E)-1-O-(β-D-Glucopyranosyl)-N--4-icosasphingenine (1) was synthesized from D-glucose, L-serine, 15-pentadecanolide, an linoleic acid.The high-field 1H-NMR spectrum of 1 was identical with that of the esterified cere
- Mori, Kenji,Matsuda, Hiroyuki
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p. 529 - 535
(2007/10/02)
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- Process for the preparation of sphingosine derivatives
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The invention relates to a new process for the preparation of the sphingosine derivatives described in European Patent Application No. 146,810, of the formula: STR1 It comprises protecting D-galactose in the 4,6-position and oxidizing it to the corresponding D-threose protected in the 2,4-position, condensing an aliphatic chain (R3) onto the latter by a Wittig reaction, converting the free hydroxyl group into a azido group and splitting off the protective group, protecting the resulting 2-azido-1,3-dihydroxy compound selectively in the 1-position and blocking it in the 3-position, liberating the 1-hydroxy group again, glycosidating the resulting compound or the abovementioned 2-azido-1,3-dihydroxy compound with the 0-trifluoro- or 0-trichloro-acetimade or the 1-halogen derivative of a 2,3,4,6-0-tetraacyl-D-glucose, splitting off the acyl groups of these and the protective group in the 3-position, converting the azido group into an amino group and acylating the amino compound with a fatty acid R1 --OH. The process gives the compounds of the therapeutically more active D series in a high yield in relatively few stages without resolving diastereomers.
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- Stereochemistry Associated with the Addition of 2-(Trimethylsilyl)thiazole to Differentially Protected α-Amino Aldehydes. Applications toward the Synthesis of Amino Sugars ans Sphingosines
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The stereochemistry and synthetic utility of the addition of 2-(trimethylsilyl)thiazole (2-TST, 1) to various N-protected α-amino aldehydes is described.The reactions of 1 with N-Boc-L-serinal acetonide (2) and N-Boc-L-threoninal acetonide (3) are essential anti diastereoselective (ds = 85-90percent) in agreement with the Felkin-Anh model for asymmetric induction, whereas the reactions with O-benzyl-NH-Boc-L-serinal (4) and NH-Boc-L-phenylalaninal (5) are syn diastereoselective (ds = 80percent).The reversal of diastereoselectivity is interpreted on the basis of a proton-bridged cyclic Cram model for asymmetric induction.Te anti-adduct derived the N-Boc-L-serinal acetonide (2) was subjected to thiazol-to-formyl unmasking to give a one-carbon higher homologue (i. e., the O,N-protected β-amino-α-hydroxy aldehyde 6a).This material serves as a precursor to ribo- and arabino-4-amino-4-deoxypentoses via a further one-carbon-chain elongation with 2-TST and to a C20 sphingosine via Wittig olefination.The above ribo-amino sugar was transformed via sequential Wittig olefination and reduction into a C18 phytosphingosine.
- Dondoni, Alessandro,Fantin, Giancarlo,Fogagnolo, Marco,Pedrini, Paola
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p. 1439 - 1446
(2007/10/02)
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- An efficient, stereoselective synthesis of 4-E- and 4-Z-D-erythro-sphingenine and related compounds from 2-amino-2-deoxy-D-glucose.
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Efficient, stereoselective synthesis of 4-E- and 4-Z-D-erythro-sphingenines having C16, C18, and C20 carbon-chains was achieved in 13 steps, starting from allyl 2-benzyloxycarbonylamino-2-deoxy-alpha-D-glucopyranoside. 2-Amino-1,6-di-O-tert- butyldiphenylsilyl-2-N,3-O-carbonyl-2-deoxy-D -allitol was used as the key intermediate.
- Sugawara,Narisada
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p. 125 - 138
(2007/10/02)
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- Synthesis of Sphingosines, 4. - Synthesis of erythro-Sphingosines via Their Azido Derivatives
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The 2,4-O-protected D-threoses 3a and 3b were obtained from D-galactose and D-xylose, respectively, in two-step procedures.Wittig reaction in the presence of an excess of lithium bromide afforded the trans-enetriols 4aA, 4aB, and 4bA.Triflate activation of the unprotected 2-hydroxy group, azide group introduction, and cleavage of the O-protective groups yielded the azidosphingosines 6A,B which provide after azide group reduction the D-erythro-sphingosines 7A,B.For the glycosphingolipid synthesis through azidosphingosine glycosylation, compound 6A was transformed by 1-O tritylation, 3-O protection, and subsequent 1-O detritylation into the 3-O-protected azidosphingosines 11α-11γ.
- Zimmermann, Peter,Schmidt, Richard R.
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p. 663 - 668
(2007/10/02)
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- SYNTHESIS OF D-ERYTHRO-SPHINGOSINES
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2,4-Di-O-protected D-threose, readily available from D-galactose, is a versatile intermediate for D-erythro-sphingosine syntheses via trans-selective Wittig reaction, azide introduction at the unprotected hydroxylic group, and subsequent azide reduction.
- Schmidt, Richard R.,Zimmermann, Peter
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p. 481 - 484
(2007/10/02)
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