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

doi:10.3390/md14110197

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

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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 language	English
Article number	197
Journal	Marine Drugs
Volume	14
Issue number	11
DOIs	https://doi.org/10.3390/md14110197
Publication status	Published - 27 Oct 2016

Bibliographical 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 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.

Keywords

makaluvamine
Zyzzya
oxidative stress
neurons
marine sponge
nrf2

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Evaluation of the Antioxidant Activity of the Marine Pyrroloiminoquinone Makaluvamines
© 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
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Cite this

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title = "Evaluation of the Antioxidant Activity of the Marine Pyrroloiminoquinone Makaluvamines",

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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author = "Eva Alonso and Rebeca Alvari{\~n}o and Marta Leir{\'o}s and Tabudravu, {Jioji N} and Klaus Feussner and Dam, {Miriam A} and Rateb, {Mostafa E} and Marcel Jaspars and Botana, {Luis M}",

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{\textquoteright}s Seventh Framework Programme managed by REA—Research Executive Agency (FP7/2007-2013) under grant agreement 312184 PHARMASEA.",

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AU - Alonso, Eva

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AU - Leirós, Marta

AU - Tabudravu, Jioji N

AU - Feussner, Klaus

AU - Dam, Miriam A

AU - Rateb, Mostafa E

AU - Jaspars, Marcel

AU - Botana, Luis M

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.

AB - 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.

KW - makaluvamine

KW - Zyzzya

KW - oxidative stress

KW - neurons

KW - marine sponge

KW - nrf2

U2 - 10.3390/md14110197

DO - 10.3390/md14110197

M3 - Article

C2 - 27801775

SN - 1660-3397

VL - 14

JO - Marine Drugs

JF - Marine Drugs

IS - 11

M1 - 197

ER -

Evaluation of the Antioxidant Activity of the Marine Pyrroloiminoquinone Makaluvamines

Abstract

Bibliographical note

Keywords

UN SDGs

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