Evaluation of the Antioxidant Activity of the Marine Pyrroloiminoquinone Makaluvamines

被引:15
作者
Alonso, Eva [1 ]
Alvarino, Rebeca [1 ]
Leiros, Marta [1 ]
Tabudravu, Jioji N. [2 ]
Feussner, Klaus [3 ]
Dam, Miriam A. [2 ]
Rateb, Mostafa E. [2 ]
Jaspars, Marcel [2 ]
Botana, Luis M. [1 ]
机构
[1] Univ Santiago de Compostela, Fac Vet, Dept Farmacol, Lugo 27002, Spain
[2] Univ Aberdeen, Dept Chem, Marine Biodiscovery Ctr, Aberdeen AB24 3UE, Scotland
[3] Univ South Pacific, Inst Appl Sci, POB 1168, Suva, Fiji
关键词
makaluvamine; Zyzzya; oxidative stress; neurons; marine sponge; nrf2; OXIDATIVE STRESS; NATURAL-PRODUCTS; A-BETA; METABOLITES; DISEASES;
D O I
10.3390/md14110197
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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.
引用
收藏
页数:12
相关论文
共 34 条
[1]   Scavenging effects of phenolic compounds on reactive oxygen species [J].
Aboul-Enein, Hassan Y. ;
Kruk, Irena ;
Kladna, Aleksandra ;
Lichszteld, Krzysztof ;
Michalska, Teresa .
BIOPOLYMERS, 2007, 86 (03) :222-230
[2]  
Ajith Thekkuttuparambil A, 2015, Curr Aging Sci, V8, P235
[3]   13-Desmethyl spirolide-C is neuroprotective and reduces intracellular Aβ and hyperphosphorylated tau in vitro [J].
Alonso, Eva ;
Vale, Carmen ;
Vieytes, Mercedes R. ;
Laferla, Frank M. ;
Gimenez-Llort, Lydia ;
Botana, Luis M. .
NEUROCHEMISTRY INTERNATIONAL, 2011, 59 (07) :1056-1065
[4]   The Cholinergic Antagonist Gymnodimine Improves Aβ and Tau Neuropathology in an in Vitro Model of Alzheimer Disease [J].
Alonso, Eva ;
Vale, Carmen ;
Vieytes, Mercedes R. ;
Laferla, Frank M. ;
Gimenez-Llort, Lydia ;
Botana, Luis M. .
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 2011, 27 (06) :783-794
[5]   Pyrroloiminoquinone and related metabolites from marine sponges [J].
Antunes, EM ;
Copp, BR ;
Davies-Coleman, MT ;
Samaai, T .
NATURAL PRODUCT REPORTS, 2005, 22 (01) :62-72
[6]  
BARROWS LR, 1993, ANTI-CANCER DRUG DES, V8, P333
[7]   Design, Synthesis and Evaluation of New Marine Alkaloid-Derived Pentacyclic Structures with Anti-Tumoral Potency [J].
Boucle, Sebastien ;
Melin, Celine ;
Clastre, Marc ;
Guillard, Jerome .
MARINE DRUGS, 2015, 13 (01) :655-665
[8]   Recent Advances in the Treatment of Neurodegenerative Diseases Based on GSH Delivery Systems [J].
Cacciatore, Ivana ;
Baldassarre, Leonardo ;
Fornasari, Erika ;
Mollica, Adriano ;
Pinnen, Francesco .
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2012, 2012
[9]   Makaluvamine P, a new cytotoxic pyrroloiminoquinone from Zyzzya cf. fuliginosa [J].
Casapullo, A ;
Cutignano, A ;
Bruno, I ;
Bifulco, G ;
Debitus, C ;
Gomez-Paloma, L ;
Riccio, R .
JOURNAL OF NATURAL PRODUCTS, 2001, 64 (10) :1354-1356
[10]   Mitochondrial Diseases of the Brain [J].
Chaturvedi, Rajnish K. ;
Beal, M. Flint .
FREE RADICAL BIOLOGY AND MEDICINE, 2013, 63 :1-29