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Isolation and assessment of the in vitro anti-tumor activity of smenothiazole A and B, chlorinated thiazole-containing peptide/polyketides from the Caribbean sponge, Smenospongia aurea.

Esposito G, Teta R, Miceli R, Ceccarelli LS, Della Sala G, Camerlingo R, Irollo E, Mangoni A, Pirozzi G, Costantino V - Mar Drugs (2015)

Bottom Line: The study of the secondary metabolites contained in the organic extract of Caribbean sponge Smenospongia aurea led to the isolation of smenothiazole A (3) and B (4), hybrid peptide/polyketide compounds.Assays performed using four solid tumor cell lines showed that smenothiazoles exert a potent cytotoxic activity at nanomolar levels, with selectivity over ovarian cancer cells and a pro-apoptotic mechanism.

View Article: PubMed Central - PubMed

Affiliation: The NeaNat Group, Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy. germana.esposito@unina.it.

ABSTRACT
The study of the secondary metabolites contained in the organic extract of Caribbean sponge Smenospongia aurea led to the isolation of smenothiazole A (3) and B (4), hybrid peptide/polyketide compounds. Assays performed using four solid tumor cell lines showed that smenothiazoles exert a potent cytotoxic activity at nanomolar levels, with selectivity over ovarian cancer cells and a pro-apoptotic mechanism.

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Related in: MedlinePlus

HR-ESI-MS-HPLC analysis of Marfey’s derivatives from smenothiazole A (3): extracted-ion chromatograms at m/z 370.1357 of l-1-fluoro-2-4-dinitrophenyl-5-alanine amide (FDAA)-Val from 3 (a); of authentic l-FDAA-l-Val (b); and of authentic d-FDAA-l-Val (c); extracted-ion chromatograms at m/z 368.1201 of l-FDAA-Pro from 3 (d); of authentic l-FDAA-l-Pro (e); and of authentic d-FDAA-l-Pro (f).
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marinedrugs-13-00444-f004: HR-ESI-MS-HPLC analysis of Marfey’s derivatives from smenothiazole A (3): extracted-ion chromatograms at m/z 370.1357 of l-1-fluoro-2-4-dinitrophenyl-5-alanine amide (FDAA)-Val from 3 (a); of authentic l-FDAA-l-Val (b); and of authentic d-FDAA-l-Val (c); extracted-ion chromatograms at m/z 368.1201 of l-FDAA-Pro from 3 (d); of authentic l-FDAA-l-Pro (e); and of authentic d-FDAA-l-Pro (f).

Mentions: The configuration of the two double bonds was established from the NOESY spectrum. Specifically, the 14E and 18E configurations were based, respectively, on the NOESY correlations between H-19 and H2-20 and between H3-15 and H2-17. Marfey’s analysis [9] was used to determine the configuration of the two amino acids. Because of the propensity for racemization at the α carbon of thiazole-modified amino acid [10], Compound 3 was subjected to ozonolysis prior to hydrolysis and derivatization with the l-enantiomer of Marfey’s reagent (FDAA, or 1-fluoro-2-4-dinitrophenyl-5-alanine amide; see the Experimental Section for details). Only 4 μg of Compound 3 were subjected to degradation, and the obtained derivatives were analyzed by high resolution ESIMS-HPLC to make the analysis as sensitive and specific as possible. In spite of the low amounts used, the extracted-ion chromatograms at m/z 370.1357 (FDAA-Val) and 368.1201 (FDAA-Pro) were almost devoid of noise (Figure 4). Both amino acids were found to have the l configuration on the basis of the retention times of their respective Marfey’s derivatives.


Isolation and assessment of the in vitro anti-tumor activity of smenothiazole A and B, chlorinated thiazole-containing peptide/polyketides from the Caribbean sponge, Smenospongia aurea.

Esposito G, Teta R, Miceli R, Ceccarelli LS, Della Sala G, Camerlingo R, Irollo E, Mangoni A, Pirozzi G, Costantino V - Mar Drugs (2015)

HR-ESI-MS-HPLC analysis of Marfey’s derivatives from smenothiazole A (3): extracted-ion chromatograms at m/z 370.1357 of l-1-fluoro-2-4-dinitrophenyl-5-alanine amide (FDAA)-Val from 3 (a); of authentic l-FDAA-l-Val (b); and of authentic d-FDAA-l-Val (c); extracted-ion chromatograms at m/z 368.1201 of l-FDAA-Pro from 3 (d); of authentic l-FDAA-l-Pro (e); and of authentic d-FDAA-l-Pro (f).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4306946&req=5

marinedrugs-13-00444-f004: HR-ESI-MS-HPLC analysis of Marfey’s derivatives from smenothiazole A (3): extracted-ion chromatograms at m/z 370.1357 of l-1-fluoro-2-4-dinitrophenyl-5-alanine amide (FDAA)-Val from 3 (a); of authentic l-FDAA-l-Val (b); and of authentic d-FDAA-l-Val (c); extracted-ion chromatograms at m/z 368.1201 of l-FDAA-Pro from 3 (d); of authentic l-FDAA-l-Pro (e); and of authentic d-FDAA-l-Pro (f).
Mentions: The configuration of the two double bonds was established from the NOESY spectrum. Specifically, the 14E and 18E configurations were based, respectively, on the NOESY correlations between H-19 and H2-20 and between H3-15 and H2-17. Marfey’s analysis [9] was used to determine the configuration of the two amino acids. Because of the propensity for racemization at the α carbon of thiazole-modified amino acid [10], Compound 3 was subjected to ozonolysis prior to hydrolysis and derivatization with the l-enantiomer of Marfey’s reagent (FDAA, or 1-fluoro-2-4-dinitrophenyl-5-alanine amide; see the Experimental Section for details). Only 4 μg of Compound 3 were subjected to degradation, and the obtained derivatives were analyzed by high resolution ESIMS-HPLC to make the analysis as sensitive and specific as possible. In spite of the low amounts used, the extracted-ion chromatograms at m/z 370.1357 (FDAA-Val) and 368.1201 (FDAA-Pro) were almost devoid of noise (Figure 4). Both amino acids were found to have the l configuration on the basis of the retention times of their respective Marfey’s derivatives.

Bottom Line: The study of the secondary metabolites contained in the organic extract of Caribbean sponge Smenospongia aurea led to the isolation of smenothiazole A (3) and B (4), hybrid peptide/polyketide compounds.Assays performed using four solid tumor cell lines showed that smenothiazoles exert a potent cytotoxic activity at nanomolar levels, with selectivity over ovarian cancer cells and a pro-apoptotic mechanism.

View Article: PubMed Central - PubMed

Affiliation: The NeaNat Group, Dipartimento di Farmacia, Università degli Studi di Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy. germana.esposito@unina.it.

ABSTRACT
The study of the secondary metabolites contained in the organic extract of Caribbean sponge Smenospongia aurea led to the isolation of smenothiazole A (3) and B (4), hybrid peptide/polyketide compounds. Assays performed using four solid tumor cell lines showed that smenothiazoles exert a potent cytotoxic activity at nanomolar levels, with selectivity over ovarian cancer cells and a pro-apoptotic mechanism.

Show MeSH
Related in: MedlinePlus