Browsing by Author "Faundez, Mario"

Now showing 1 - 11 of 11
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    Design, synthesis, cytotoxicity and 3D-QSAR analysis of new 3,6-disubstituted-1,2,4,5-tetrazine derivatives as potential antitumor agents
    (2017) Cañete Molina, Álvaro; Espinosa Bustos, Christian Marcelo; González Castro, Marcos; Faundez, Mario; Mella, Jaime; Tapia Apati, Ricardo; Cabrera Caballero, Alan Raúl; Brito, Iván; Aguirre, Adam; Salas Sánchez, Cristián Osvaldo
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    Effect of alpha lipoic acid on leukotriene A(4) hydrolase
    (2017) Torres, M.; Fierro Huerta, Angélica; Pessoa Mahana, Carlos David; Romero, J.; Cabrera, G.; Faundez, Mario
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    In vitro activity and mechanism of action against the protozoan parasite Trypanosoma cruzi of 5-nitrofuryl containing thiosemicarbazones
    (2004) Aguirre, Gabriela; Boiani, Lucia; Cerecetto, Hugo; Fernandez, Marcelo; Gonzalez, Mercedes; Denicola, Ana; Otero, Lucia; Gambino, Dinorah; Rigol, Carolina; Faundez, Mario; Olea-Azar, Claudio
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    Melatonin protects the cytochrome P450 system through a novel antioxidant mechanism
    (ELSEVIER IRELAND LTD, 2010) Eugenia Letelier, Maria; Jara Sandoval, Jose; Molina Berrios, Alfredo; Faundez, Mario; Aracena Parks, Paula; Aguilera, Felipe
    Melatonin, an endogenous hormone, is used as an antioxidant drug in doses quite higher than the endogenous circulating levels of this hormone. Hepatic endoplasmic reticulum contains the cytochrome P450 (CYP450) system, which catalyzes one biotransformation pathway of melatonin; this organelle is also one of the main sources of reactive oxygen species in cells. Therefore, we proposed that the antioxidant activity of this hormone may have a biological relevance in the organelle where it is biotransformed. To evaluate this postulate, we used Fe3+/ascorbate, an oxygen free radical generating system that leads to lipid peroxidation, loss of protein-thiol content, and activation of UDP-glucuronyltransferase in rat liver microsomes. We found that mM concentrations of melatonin prevented all these oxidative phenomena. We also found that Fe3+/ascorbate leads to structural alterations in the CYP450 monooxygenase, the enzyme that binds the substrate in the CYP450 system catalytic cycle, probably through direct oxidation of the protein, and also inhibited p-nitroanisole O-demethylation, a reaction catalyzed by the CYP450 system. Notably, melatonin prevented both phenomena at mu M concentrations. We provide evidence suggesting that melatonin may be oxidized by oxygen free radicals. Thus, we postulate that melatonin may be acting as an oxygen free radical scavenger, and Fe3+/ascorbate-modified melatonin would be directly protecting the CYP450 system through an additional specific mechanism. Pharmacological relevance of this phenomenon is discussed. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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    Microwave Assisted Synthesis of Novel Six-Membered 4-C, 4-O and 4-S Lactams Derivatives: Characterization and in vitro Biological Evaluation of Cytotoxicity and Anticoagulant Activity
    (2017) Núñez Navarro, Nicolás Ernesto; Segovia Bonnemaison, Gerardine Francoise; Burgos, Renato; Lagos, Carlos; Fuentes, Nataly; Faundez, Mario; Zacconi, Flavia C. M.
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    NADPH oxidase activity: Spectrophotometric determination of superoxide using pyrogallol red
    (2017) Cortes, J.; Torres, M.; Campos, M.; Romero, J.; Letelier, M.; Pessoa Mahana, Carlos David; Chung, H.; Faundez, Mario
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    New imidoyl-indazole platinum (II) complexes as potential anticancer agents: Synthesis, evaluation of cytotoxicity, cell death and experimentaltheoretical DNA interaction studies
    (2017) Cabrera Caballero, Alan Raúl; Espinosa Bustos, Christian Marcelo; Faundez, Mario; Meléndez Rojel, Jaime Gumercindo; Jaque Olmedo, Pablo César; Daniliuc, Constantin G.; Aguirre Ducler, Adam Jesús; Rojas Guerrero, René; Salas Sánchez, Cristián Osvaldo
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    New Pyridone-Based Derivatives as Cannabinoid Receptor Type 2 Agonists
    (MDPI, 2021) Faundez Parraguez, Manuel; Alarcon Miranda, Carlos; Cho, Young Hwa; Pessoa Mahana, Hernan; Gallardo Garrido, Carlos; Chung, Hery; Faundez, Mario; Pessoa Mahana, David
    The activation of the human cannabinoid receptor type II (CB2R) is known to mediate analgesic and anti-inflammatory processes without the central adverse effects related to cannabinoid receptor type I (CB1R). In this work we describe the synthesis and evaluation of a novel series of N-aryl-2-pyridone-3-carboxamide derivatives tested as human cannabinoid receptor type II (CB2R) agonists. Different cycloalkanes linked to the N-aryl pyridone by an amide group displayed CB2R agonist activity as determined by intracellular [cAMP] levels. The most promising compound 8d exhibited a non-toxic profile and similar potency (EC50 = 112 nM) to endogenous agonists Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) providing new information for the development of small molecules activating CB2R. Molecular docking studies showed a binding pose consistent with two structurally different agonists WIN-55212-2 and AM12033 and suggested structural requirements on the pyridone substituents that can satisfy the orthosteric pocket and induce an agonist response. Our results provide additional evidence to support the 2-pyridone ring as a suitable scaffold for the design of CB2R agonists and represent a starting point for further optimization and development of novel compounds for the treatment of pain and inflammation.
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    Novel FXa Inhibitor identification through integration of ligand- and structure-based approaches
    (2017) Lagos, C.; Segovia Bonnemaison, Gerardine Francoise; Núñez Navarro, Nicolás Ernesto; Faundez, Mario; Zacconi, Flavia C. M.
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    Synthesis, binding assays, cytotoxic activity and docking studies of benzimidazole and benzothiophene derivatives with selective affinity for the CB2 cannabinoid receptor
    (2016) Romero Parra, Javier Hernán; Mella Raipán, Jaime Alberto; Palmieri, Vittoria; Allarà, Marco; Torres Torres, María José; Pessoa Mahana, Hernán; Iturriaga Vásquez, Patricio; Escobar, Rossy; Faundez, Mario; Di Marzo, Vicenzo; Pessoa Mahana, Carlos David
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    Trypanosoma cruzi: In vitro effect of aspirin with nifurtimox and benznidazole
    (ACADEMIC PRESS INC ELSEVIER SCIENCE, 2010) Lopez Munoz, Rodrigo; Faundez, Mario; Klein, Sebastian; Escanilla, Sebastian; Torres, Gloria; Lee Liu, Dasfne; Ferreira, Jorge; Kemmerling, Ulrike; Orellana, Myriam; Morello, Antonio; Ferreira, Arturo; Maya, Juan D.
    Nifurtimox and benznidazole are the only active drugs against Trypanosoma cruzi; however, they have limited efficacy and severe side effects. During primoinfection, T cruzi infected macrophages mount an antiparasitic response, which the parasite evades through an increase of tumor growth factor beta and PGE(2) activation as well as decreased iNOS activity. Thus, prostaglandin synthesis inhibition with aspirin might increase macrophage antiparasitic activity and increase nifurtimox and benznidazole effect.