The spirolide content of massive cultures of Alexandrium ostenfeldii1 collected along the North-western Adriatic coasts of Italy in November 2003 was determined by Liquid Chromatography- Mass Spectrometry and 1D- and 2D-NMR techniques. Among the detected spirolides, three resulted major compounds and were unambiguously identified as 13-desmethyl spirolide C2, 13,19-didesmethyl spirolide C3 and 27-hydroxy-13,19-didesmethyl spirolide C4. During our ongoing studies on Adriatic A. ostenfeldii, we have recently succeeded in elucidating the full relative stereochemistry of 13,19-didesmethyl spirolide C through NMR- and Molecular Modeling-based techniques. Besides this, our studies have also contributed to shed some light upon 13,19-didesmethyl spirolide C conformational behavior in solution. This could pave the way towards a more in-depth comprehension of spirolide mechanism of action. In fact, so far pharmacological studies have identified spirolides as fast-acting toxins5, as in the mouse bioassay they induce rapid onset of symptoms akin to those reported for the acute toxicity of paralytic shellfish poisoning (PSP) toxins, followed by death within minutes from the intraperitoneal injection. It has been shown that spirolides affect Ca2+ channels and hypothesized that their pharmacophore is represented by the uncommon cyclic imine moiety. Beyond this information, though, spirolide toxicity is far from being totally and unambiguously defined. 1) Ciminiello, P., Dell'Aversano, C., Fattorusso, E., Magno, S., Tartaglione, L., Cangini, M., Pompei, M., Guerrini, F., Boni, L., Pistocchi, R. (2006). Toxicon 47, 597-604. 2) T. Hu, I. W. Burton, A. D. Cembella, J. M. Curtis, M. A. Quilliam, J. A. Walter and J. L. C. Wright, J. Nat. Prod., 2001, 64, 308. 3) S. L. MacKinnon, J. A. Walter, M. A. Quilliam, A. D. Cembella, P. LeBlanc, I. W. Burton, W. R. Hardstaff and N. I. Lewis, J. Nat. Prod., 2006, 69, 983. 4) P. Ciminiello, C. Dell'Aversano, E. Fattorusso, M. Forino, L. Grauso, L. Tartaglione, F. Guerrini, and R. Pistocchi, J. Nat. Prod., 2007, 70, 1878. 5) Richard, D., Arsenault, E., Cembella, A., Quilliam, M. A. (2000) In Intergovernmental Oceanographic Commission of UNESCO: Harmful Algal Blooms 2000. (Hallegraeff, G. M., Blackburn, S. I., Bolch, C. J., Lewis, R. J., Eds.) pp. 383-386.
Full relative stereochemistry assignment and conformational analysis of 13,19-didesmethyl spirolide C via NMR- and Molecular Modeling-based techniques. A step towards the comprehension of spirolide mechanism of action / Grauso, L.; Ciminiello, Patrizia; Catalanotti, Bruno; Dell'Aversano, Carmela; DELLO IACOVO, Emma; Fattorusso, Caterina; Fattorusso, E.; Forino, Martino; Leo, A.; Tartaglione, Luciana. - (2009), pp. 81-81. (Intervento presentato al convegno 6th European Conference on Marine Natural Products tenutosi a Porto, Portugal nel 19-23 luglio).
Full relative stereochemistry assignment and conformational analysis of 13,19-didesmethyl spirolide C via NMR- and Molecular Modeling-based techniques. A step towards the comprehension of spirolide mechanism of action.
L. Grauso;CIMINIELLO, PATRIZIA;CATALANOTTI, BRUNO;DELL'AVERSANO, CARMELA;DELLO IACOVO, EMMA;FATTORUSSO, CATERINA;FORINO, MARTINO;TARTAGLIONE, LUCIANA
2009
Abstract
The spirolide content of massive cultures of Alexandrium ostenfeldii1 collected along the North-western Adriatic coasts of Italy in November 2003 was determined by Liquid Chromatography- Mass Spectrometry and 1D- and 2D-NMR techniques. Among the detected spirolides, three resulted major compounds and were unambiguously identified as 13-desmethyl spirolide C2, 13,19-didesmethyl spirolide C3 and 27-hydroxy-13,19-didesmethyl spirolide C4. During our ongoing studies on Adriatic A. ostenfeldii, we have recently succeeded in elucidating the full relative stereochemistry of 13,19-didesmethyl spirolide C through NMR- and Molecular Modeling-based techniques. Besides this, our studies have also contributed to shed some light upon 13,19-didesmethyl spirolide C conformational behavior in solution. This could pave the way towards a more in-depth comprehension of spirolide mechanism of action. In fact, so far pharmacological studies have identified spirolides as fast-acting toxins5, as in the mouse bioassay they induce rapid onset of symptoms akin to those reported for the acute toxicity of paralytic shellfish poisoning (PSP) toxins, followed by death within minutes from the intraperitoneal injection. It has been shown that spirolides affect Ca2+ channels and hypothesized that their pharmacophore is represented by the uncommon cyclic imine moiety. Beyond this information, though, spirolide toxicity is far from being totally and unambiguously defined. 1) Ciminiello, P., Dell'Aversano, C., Fattorusso, E., Magno, S., Tartaglione, L., Cangini, M., Pompei, M., Guerrini, F., Boni, L., Pistocchi, R. (2006). Toxicon 47, 597-604. 2) T. Hu, I. W. Burton, A. D. Cembella, J. M. Curtis, M. A. Quilliam, J. A. Walter and J. L. C. Wright, J. Nat. Prod., 2001, 64, 308. 3) S. L. MacKinnon, J. A. Walter, M. A. Quilliam, A. D. Cembella, P. LeBlanc, I. W. Burton, W. R. Hardstaff and N. I. Lewis, J. Nat. Prod., 2006, 69, 983. 4) P. Ciminiello, C. Dell'Aversano, E. Fattorusso, M. Forino, L. Grauso, L. Tartaglione, F. Guerrini, and R. Pistocchi, J. Nat. Prod., 2007, 70, 1878. 5) Richard, D., Arsenault, E., Cembella, A., Quilliam, M. A. (2000) In Intergovernmental Oceanographic Commission of UNESCO: Harmful Algal Blooms 2000. (Hallegraeff, G. M., Blackburn, S. I., Bolch, C. J., Lewis, R. J., Eds.) pp. 383-386.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
