title: Evaluation of the Antioxidant Activity of the Marine Pyrroloiminoquinone Makaluvamines.
abstract: Makaluvamines are pyrroloiminoquinones isolated fromZyzzyasponges. 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 ap-hydroxystyryl without a double bond seems to be the most active structure with a complete antioxidant effect in neuronal cells.
authors: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo 27002, Spain. eva.alonso@usc.es.
authors: Eva
authors: E
authors: Alonso
authors: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo 27002, Spain. rebeca.alvarino@usc.es.
authors: Rebeca
authors: R
authors: Alvariño
authors: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo 27002, Spain. marta.leiros@usc.es.
authors: Marta
authors: M
authors: Leirós
authors: Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, MestonWalk, Aberdeen AB24 3UE, UK. j.tabudravu@abdn.ac.uk.
authors: Jioji N
authors: JN
authors: Tabudravu
authors: Institute of Applied Sciences, University of the South Pacific, P.O. Box 1168, Suva, Fiji. Feussner_k@usp.ac.fj.
authors: Klaus
authors: K
authors: Feussner
authors: Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, MestonWalk, Aberdeen AB24 3UE, UK. miriam.dam@abdn.ac.uk.
authors: Miriam A
authors: MA
authors: Dam
authors: Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, MestonWalk, Aberdeen AB24 3UE, UK. Mostafa.rateb@uws.ac.uk.
authors: Mostafa E
authors: ME
authors: Rateb
authors: Marine Biodiscovery Centre, Department of Chemistry, University of Aberdeen, MestonWalk, Aberdeen AB24 3UE, UK. m.jaspars@abdn.ac.uk.
authors: Marcel
authors: M
authors: Jaspars
authors: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo 27002, Spain. luis.botana@usc.es.
authors: Luis M
authors: LM
authors: Botana
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D011161:Porifera / Q000737:chemistry*; D011247:Pregnancy; D061251:Primary Cell Culture; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology*; D047608:Pyrroloiminoquinones / Q000494:pharmacology*; D015363:Quinolones / Q000737:chemistry* / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; D011758:Pyrroles; D047608:Pyrroloiminoquinones; D015363:Quinolones; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D005978:Glutathione
keywords: Zyzzya; makaluvamine; marine sponge; neurons; nrf2; oxidative stress