Person: Marco Contelles, José Luis
Loading...
First Name
José Luis
Last Name
Marco Contelles
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Area
Química Orgánica
Identifiers
7 results
Search Results
Now showing 1 - 7 of 7
Item Nucleobase-Derived Nitrones: Synthesis and Antioxidant and Neuroprotective Activities in an In Vitro Model of Ischemia–Reperfusion(International Journal of Molecular Sciences, 2022) Chamorro, Beatriz; Głowacka, Iwona E.; Gotkowska, Joanna; Gulej, Rafał; Hadjipavlou Litina, Dimitra; López Muñoz, Francisco; Marco Contelles, José Luis; Piotrowska, Dorota G.; Oset Gasque, María JesúsHerein, we report the synthesis, antioxidant, and neuroprotective properties of some nucleobase-derived nitrones named 9a–i. The neuroprotective properties of nitrones, 9a–i, were measured against an oxygen-glucose-deprivation in vitro ischemia model using human neuroblastoma SH-SY5Y cells. Our results indicate that nitrones, 9a–i, have better neuroprotective and antioxidant properties than α-phenyl-N-tert-butylnitrone (PBN) and are similar to N-acetyl-L-cysteine (NAC), a well-known antioxidant and neuroprotective agent. The nitrones with the highest neuroprotective capacity were those containing purine nucleobases (nitrones 9f, g, B = adenine, theophylline), followed by nitrones with pyrimidine nucleobases with H or F substituents at the C5 position (nitrones 9a, c). All of these possess EC50 values in the range of 1–6 μM and maximal activities higher than 100%. However, the introduction of a methyl substituent (nitrone 9b, B = thymine) or hard halogen substituents such as Br and Cl (nitrones 9d, e, B = 5-Br and 5-Cl uracil, respectively) worsens the neuroprotective activity of the nitrone with uracil as the nucleobase (9a). The effects on overall metabolic cell capacity were confirmed by results on the high anti-necrotic (EC50′s ≈ 2–4 μM) and antioxidant (EC50′s ≈ 0.4–3.5 μM) activities of these compounds on superoxide radical production. In general, all tested nitrones were excellent inhibitors of superoxide radical production in cultured neuroblastoma cells, as well as potent hydroxyl radical scavengers that inhibit in vitro lipid peroxidation, particularly, 9c, f, g, presenting the highest lipoxygenase inhibitory activity among the tested nitrones. Finally, the introduction of two nitrone groups at 9a and 9d (bis-nitronas 9g, i) did not show better neuroprotective effects than their precursor mono-nitrones. These results led us to propose nitrones containing purine (9f, g) and pyrimidine (9a, c) nucleobases as potential therapeutic agents for the treatment of cerebral ischemia and/or neurodegenerative diseases, leading us to further investigate their effects using in vivo models of these pathologies.Item The Antioxidant Additive Approach for Alzheimer’s Disease Therapy: New Ferulic (Lipoic) Acid Plus Melatonin Modified Tacrines as Cholinesterases Inhibitors, Direct Antioxidants, and Nuclear Factor (Erythroid-Derived 2)-Like 2 Activators(Journal of Medicinal Chemistry, 2016) Benchekroun, Mohamed; Romero Hernández, Alejandro; Egea, Javier; León Martínez, Rafael; Michalska Dziama, Patrycja; Buendía, Izaskun; Jimeno, María Luisa; Jun, Daniel; Janockova, Jana; Sepsova, Vendula; Soukup, Ondrej; Bautista-Aguilera, Oscar M.; Refouvelet, Bernard; Ouari, Olivier; Marco Contelles, José Luis; Ismaili, LhassaneNovel multifunctional tacrines for Alzheimer’s disease were obtained by Ugi-reaction between ferulic (or lipoic acid), a melatonin-like isocyanide, formaldehyde, and tacrine derivatives, according to the antioxidant additive approach in order to modulate the oxidative stress as therapeutic strategy. Compound 5c has been identified as a promising permeable agent showing excellent antioxidant properties, strong cholinesterase inhibitory activity, less hepatotoxicity than tacrine, and the best neuroprotective capacity, being able to significantly activate the Nrf2 transcriptional pathway.- Project number: 165
Item Página web orientada a la evaluación “in silico” de nuevas sustancias con interés biológico IV(2021) Ramos Alonso, Eva; Romero Martínez, Manuel Alejandro; García Cantón, Carolina; Marco Contelles, José Luis; Pita Pita, Rene; Rodríguez Martín, Abigail; Rodríguez Talavera, María Item Neuroprotection by Phytoestrogens in the Model of Deprivation and Resupply of Oxygen and Glucose In Vitro: The Contribution of Autophagy and Related Signaling Mechanisms(Antioxidants, 2020) Abbruzzese, Giuseppe; Morón Oset, Javier; Díaz Castroverde, Sabela; García Font, Nuria; Roncero Romero, Cesáreo; López Muñoz, Francisco; Marco Contelles, José Luis; Oset Gasque, María JesúsPhytoestrogens can have a neuroprotective effect towards ischemia-reperfusion-induced neuronal damage. However, their mechanism of action has not been well described. In this work, we investigate the type of neuronal cell death induced by oxygen and glucose deprivation (OGD) and resupply (OGDR) and pinpoint some of the signaling mechanisms whereby the neuroprotective effects of phytoestrogens occur in these conditions. First, we found that autophagy initiation affords neuronal protection upon neuronal damage induced by OGD and OGDR. The mammalian target of rapamycin/ribosomal S6 kinase (mTOR/S6K) pathway is blocked in these conditions, and we provide evidence that this is mediated by modulation of both the 50 AMP-activated protein kinase (AMPK) and phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathways. These are dampened up or down, respectively, under OGDR-induced neuronal damage. In contrast, the MAPK-Erk kinase/extracellular signal-regulated kinase (MEK/ERK) pathway is increased under these conditions. Regarding the pathways affected by phytoestrogens, we show that their protective properties require autophagy initiation, but at later stages, they decrease mitogen-activated protein kinase (MAPK) and AMPK activation and increase mTOR/S6K activation. Collectively, our results put forward a novel mode of action where phytoestrogens play a dual role in the regulation of autophagy by acting as autophagy initiation enhancers when autophagy is a neuroprotective and pro-survival mechanism, and as autophagy initiation inhibitors when autophagy is a pro-death mechanism. Finally, our results support the therapeutic potential of phytoestrogens in brain ischemia by modulating autophagy.- Project number: 150
Item Página web orientada a la evaluación in silico de nuevas sustancias con interés biológico (parte V)(2022) Ramos Alonso, Eva; Romero Martínez, Manuel Alejandro; García Cantón, Carolina; Pita Pita, Rene; Rodríguez Martín, Abigail; Rodríguez Talavera, María; Marco Contelles, José Luis - Project number: 190
Item Página web orientada a la evaluación in silico de nuevas sustancias con interés biológico (parte VI)(2023) Ramos Alonso, Eva; Marco Contelles, José Luis; Pita Pita, Rene; Rodríguez Martín, Abigail; Rodriguez Talavera, María; Egea, Javier; Paramo Muñoz, Ana; Ríos, Cristóbal de los; Romero Martínez, Manuel Alejandro; García Cantón, CarolinaEn la línea de las ediciones anteriores, los resultados obtenidos con el proyecto "INSILITOX" han sido muy positivos. Por esta razón, el equipo se ha propuesto continuar optimizando la página web añadiendo nuevos recursos que apoyen la formación de los estudiantes, tanto de Grado como de Posgrado, en este entorno multilingüe de aprendizaje virtual adaptativo. - Project number: 101
Item Página web orientada a la evaluación “in silico” de nuevas sustancias con interés biológico. Parte III(2020) Ramos Alonso, Eva; Romero Martínez, Manuel Alejandro; Rodríguez Martín, Abigail; Rodríguez Talavera, María; Marco Contelles, José Luis; García Cantón, Carolina; Pita Pita, Rene