Evaluation of the Antioxidant Activity of the Marine Pyrroloiminoquinone Makaluvamines

Eva Alonso, Rebeca Alvariño, Marta Leirós, Jioji N Tabudravu, Klaus Feussner, Miriam A Dam, Mostafa E Rateb, Marcel Jaspars, Luis M Botana

Research output: Contribution to journalArticle

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Abstract

Makaluvamines are pyrroloiminoquinones isolated from Zyzzya sponges. Until now, they have been described as topoisomerase II inhibitors with cytotoxic effects in diverse tumor cell lines. In the present work, seven makaluvamines were tested in several antioxidant assays in primary cortical neurons and neuroblastoma cells. Among the alkaloids studied, makaluvamine J was the most active in all the assays. This compound was able to reduce the mitochondrial damage elicited by the well-known stressor H₂O₂. The antioxidant properties of makaluvamine J are related to an improvement of the endogenous antioxidant defenses of glutathione and catalase. SHSY5Y assays proved that this compound acts as a Nrf2 activator leading to an improvement of antioxidant defenses. A low concentration of 10 nM is able to reduce the reactive oxygen species release and maintain a correct mitochondrial function. Based on these results, non-substituted nitrogen in the pyrrole plus the presence of a p-hydroxystyryl without a double bond seems to be the most active structure with a complete antioxidant effect in neuronal cells.

Original languageEnglish
Article number197
JournalMarine Drugs
Volume14
Issue number11
DOIs
Publication statusPublished - 27 Oct 2016

Fingerprint

Pyrroloiminoquinones
Antioxidants
Topoisomerase II Inhibitors
Pyrroles
Porifera
Tumor Cell Line
Neuroblastoma
Alkaloids
Catalase
Glutathione
Reactive Oxygen Species
Nitrogen
Neurons

Keywords

  • makaluvamine
  • Zyzzya
  • oxidative stress
  • neurons
  • marine sponge
  • nrf2

Cite this

Alonso, E., Alvariño, R., Leirós, M., Tabudravu, J. N., Feussner, K., Dam, M. A., ... Botana, L. M. (2016). Evaluation of the Antioxidant Activity of the Marine Pyrroloiminoquinone Makaluvamines. Marine Drugs, 14(11), [197]. https://doi.org/10.3390/md14110197

Evaluation of the Antioxidant Activity of the Marine Pyrroloiminoquinone Makaluvamines. / Alonso, Eva; Alvariño, Rebeca; Leirós, Marta; Tabudravu, Jioji N; Feussner, Klaus; Dam, Miriam A; Rateb, Mostafa E; Jaspars, Marcel; Botana, Luis M.

In: Marine Drugs, Vol. 14, No. 11, 197, 27.10.2016.

Research output: Contribution to journalArticle

Alonso, E, Alvariño, R, Leirós, M, Tabudravu, JN, Feussner, K, Dam, MA, Rateb, ME, Jaspars, M & Botana, LM 2016, 'Evaluation of the Antioxidant Activity of the Marine Pyrroloiminoquinone Makaluvamines', Marine Drugs, vol. 14, no. 11, 197. https://doi.org/10.3390/md14110197
Alonso, Eva ; Alvariño, Rebeca ; Leirós, Marta ; Tabudravu, Jioji N ; Feussner, Klaus ; Dam, Miriam A ; Rateb, Mostafa E ; Jaspars, Marcel ; Botana, Luis M. / Evaluation of the Antioxidant Activity of the Marine Pyrroloiminoquinone Makaluvamines. In: Marine Drugs. 2016 ; Vol. 14, No. 11.
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abstract = "Makaluvamines are pyrroloiminoquinones isolated from Zyzzya sponges. Until now, they have been described as topoisomerase II inhibitors with cytotoxic effects in diverse tumor cell lines. In the present work, seven makaluvamines were tested in several antioxidant assays in primary cortical neurons and neuroblastoma cells. Among the alkaloids studied, makaluvamine J was the most active in all the assays. This compound was able to reduce the mitochondrial damage elicited by the well-known stressor H₂O₂. The antioxidant properties of makaluvamine J are related to an improvement of the endogenous antioxidant defenses of glutathione and catalase. SHSY5Y assays proved that this compound acts as a Nrf2 activator leading to an improvement of antioxidant defenses. A low concentration of 10 nM is able to reduce the reactive oxygen species release and maintain a correct mitochondrial function. Based on these results, non-substituted nitrogen in the pyrrole plus the presence of a p-hydroxystyryl without a double bond seems to be the most active structure with a complete antioxidant effect in neuronal cells.",
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note = "Acknowledgments The research leading to these results received funding from the following FEDER cofounded-grants. From CDTI and Technological Funds, supported by the Ministerio de Econom{\'i}a y Competitividad, AGL2012-40185-CO2-01, AGL2014-58210-R, and the Conseller{\'i}a de Cultura, Educaci{\'o}n e Ordenaci{\'o}n Universitaria, GRC2013-016, and through the Axencia Galega de Innovaci{\'o}n, Spain, ITC-20133020 SINTOX. From CDTI under ISIP Programme, Spain, IDI-20130304 APTAFOOD. From the European Union’s Seventh Framework Programme managed by REA—Research Executive Agency (FP7/2007-2013) under grant agreement 312184 PHARMASEA.",
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AU - Rateb, Mostafa E

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N1 - Acknowledgments The research leading to these results received funding from the following FEDER cofounded-grants. From CDTI and Technological Funds, supported by the Ministerio de Economía y Competitividad, AGL2012-40185-CO2-01, AGL2014-58210-R, and the Consellería de Cultura, Educación e Ordenación Universitaria, GRC2013-016, and through the Axencia Galega de Innovación, Spain, ITC-20133020 SINTOX. From CDTI under ISIP Programme, Spain, IDI-20130304 APTAFOOD. From the European Union’s Seventh Framework Programme managed by REA—Research Executive Agency (FP7/2007-2013) under grant agreement 312184 PHARMASEA.

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N2 - Makaluvamines are pyrroloiminoquinones isolated from Zyzzya sponges. Until now, they have been described as topoisomerase II inhibitors with cytotoxic effects in diverse tumor cell lines. In the present work, seven makaluvamines were tested in several antioxidant assays in primary cortical neurons and neuroblastoma cells. Among the alkaloids studied, makaluvamine J was the most active in all the assays. This compound was able to reduce the mitochondrial damage elicited by the well-known stressor H₂O₂. The antioxidant properties of makaluvamine J are related to an improvement of the endogenous antioxidant defenses of glutathione and catalase. SHSY5Y assays proved that this compound acts as a Nrf2 activator leading to an improvement of antioxidant defenses. A low concentration of 10 nM is able to reduce the reactive oxygen species release and maintain a correct mitochondrial function. Based on these results, non-substituted nitrogen in the pyrrole plus the presence of a p-hydroxystyryl without a double bond seems to be the most active structure with a complete antioxidant effect in neuronal cells.

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KW - marine sponge

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