Browsing by Author "Espinosa Bustos, Christian Marcelo"

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    2-Phenylaminonaphthoquinones and related compounds : synthesis, trypanocidal and cytotoxic activities
    (2014) Sieveking, Ivan; Thomas Riveros, Pablo Ignacio; Estévez, Juan C.; Quiñones, Natalia; Cuéllar, Mauricio A.; Villena, Juan; Espinosa Bustos, Christian Marcelo; Fierro Huerta, Angélica; Tapia Apati, Ricardo; Salas, Cristian A.
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    3D-QSAR Design of New Bcr-Abl Inhibitors Based on Purine Scaffold and Cytotoxicity Studies on CML Cell Lines Sensitive and Resistant to Imatinib
    (2025) Cabezas, David; Delgado Aguilar, Thalía; Sepúlveda Sánchez, Guisselle Alexandra; Krňávková, Petra; Vojáčková, Veronika; Kryštof, Vladimír; Strnad, Miroslav; Nicolás Ignacio, Silva Reyes; Echeverría, Javier; Espinosa Bustos, Christian Marcelo; Mellado, Guido; Luo, Jiao; Mella, Jaime; Salas Sánchez, Cristian Osvaldo
    Bcr-Abl inhibitors such as imatinib have been used to treat chronic myeloid leukemia (CML). However, the efficacy of these drugs has diminished due to mutations in the kinase domain, notably the T315I mutation. Therefore, in this study, new purine derivatives were designed as Bcr-Abl inhibitors based on 3D-QSAR studies. Methods: A database of 58 purines that inhibit Bcr-Abl was used to construct 3D-QSAR models. Using chemical information from these models, a small group of new purines was designed, synthesized, and evaluated in Bcr-Abl. Viability assays were conducted on imatinib-sensitive CML cells (K562 and KCL22) and imatinib-resistant cells (KCL22-B8). In silico analyses were performed to confirm the results. Results: Seven purines were easily synthesized (7a–g). Compounds 7a and 7c demonstrated the highest inhibition activity on Bcr-Abl (IC50 = 0.13 and 0.19 μM), surpassing the potency of imatinib (IC50 = 0.33 μM). 7c exhibited the highest potency, with GI50 = 0.30 μM on K562 cells and 1.54 μM on KCL22 cells. The GI50 values obtained for non-neoplastic HEK293T cells indicated that 7c was less toxic than imatinib. Interestingly, KCL22-B8 cells (expressing Bcr-AblT315I) showed greater sensitivity to 7e and 7f than to imatinib (GI50 = 13.80 and 15.43 vs. >20 μM, respectively). In silico analyses, including docking and molecular dynamics studies of Bcr-AblT315I, were conducted to elucidate the enhanced potency of 7e and 7f. Thus, this study provides in silico models to identify novel inhibitors that target a kinase of significance in CML.
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    A convenient and simple synthesis of N-arylpirrolopyrimidines using boronic acids and promoted by copper (II) acetate
    (2017) Espinosa Bustos, Christian Marcelo; Villegas Menares, Alondra Elena; Salas Sánchez, Cristián Osvaldo
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    Comparative Study of Phenolic Content and Antioxidant and Hepatoprotective Activities of Unifloral Quillay Tree (Quillaja saponaria Molina) and Multifloral Honeys from Chile
    (2024) Núñez Pizarro, Paula; Montenegro Rizzardini, Gloria; Núñez Quijada, Gabriel Israel; Andía Kohnenkampf, Marcelo Edgardo; Espinosa Bustos, Christian Marcelo; de Camargo, Adriano Costa; Oyarzún Isamitt, Juan Esteban; Bridi, Raquel
    Honey is a natural sweet element that bees make with flower nectar, revered for its distinct flavor, nutritional value, and potential health benefits. Chilean beekeeping has a diverse range of honey varieties, many of which are unique. The quillay (Quillaja saponaria Molina, soapbark tree) is a Chilean endemic tree whose honey has not been studied in depth. We characterized various Chilean honeys with different botanical origins, with a particular focus on quillay tree honey, analyzing its total phenolic and flavonoid content and its antioxidant activities. Cytotoxicity and hepatoprotective activity were also evaluated using HuH-7 cells. The Spearman correlation between the percentage of quillay pollen in the honey samples and the total phenolic content (R = 0.72; p < 0.05), plus the oxygen radical absorbance capacity, suggests that compounds from quillay contribute to the overall antioxidant capacity of honey. Unifloral quillay honey extracts also protect hepatic cells from oxidative damage induced by peroxyl radicals generated by AAPH. This analysis sheds light on the potential of quillay tree honey, underscoring its significance as a natural source of bioactive phenolic compounds with possible hepatoprotective effects.
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    Design, synthesis, biological evaluation and binding mode modeling of benzimidazole derivatives targeting the cannabinoid receptor type 1
    (2015) Espinosa Bustos, Christian Marcelo; Lagos, Carlos F.; Romero Parra, Javier Hernán; Zárate Méndez, Ana María; Mella Raipán, Jaime Alberto; Pessoa Mahana, Hernán; Recabarren Gajardo, Gonzalo; Iturriaga Vásquez, Patricio; Tapia Apati, Ricardo; Pessoa Mahana, Carlos David
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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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    dsDNA sensing capabilities of metallopolymers electrochemically deposited from ruthenium-pyrrole and - thiophene complexes
    (2019) Valle de la Cortina, María Angélica del; González Del Castillo, Beatriz; Espinosa Bustos, Christian Marcelo; Ramirez, A.M.; Gacitúa Santelices, Manuel Alejandro; Hernandez, L.A.
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    Enrofloxacin behavior in presence of soil extracted organic matter : an electrochemical approach
    (2017) Antilen, Mónica; Valencia, C.; Peralta, E.; Canales, C.; Espinosa Bustos, Christian Marcelo; Escudey, M.
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    Evaluation of the Membrane Permeability (PAMPA and Skin) of Benzimidazoles with Potential Cannabinoid Activity and their Relation with the Biopharmaceutics Classification System (BCS)
    (2011) Alvarez Figueroa, María Javiera; Pessoa Mahana, Carlos David; Palavecino-Gonzalez, M. Elisa; Mella Raipán, Jaime Alberto; Espinosa Bustos, Christian Marcelo; Lagos-Munoz, Manuel E.
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    First Report on Cationic Triphenylphosphonium Compounds as Mitochondriotropic H3R Ligands with Antioxidant Properties
    (2024) Werner T.; Añazco Martínez, Tito Alonso; Osses-Mendoza P.; Castro-Alvarez A.; Salas Sánchez, Cristián Osvaldo; Bridi R.; Stark H.; Espinosa Bustos, Christian Marcelo
    Neurodegenerative diseases are a major public health problem due to the aging population and multifaceted pathology; therefore, the search for new therapeutic alternatives is of the utmost importance. In this sense, a series of six 1-(3-phenoxypropyl)piperidines alkyl-linked to a triphenylphosphonium cation derivative were synthesized as H3R ligands with antioxidant properties to regulate excessive mitochondrial oxidative stress and contribute to potential new therapeutic approaches for neurodegenerative diseases. Radioligand displacement studies revealed high affinity for H3R with Ki values in the low to moderate two-digit nanomolar range for all compounds. Compound 6e showed the highest affinity (Ki H3R = 14.1 nM), comparable to that of pitolisant. Antioxidative effects were evaluated as radical-scavenging properties using the ORAC assay, in which all derivatives showed low to moderate activity. On the other hand, cytotoxic effects in SH-SY5Y neuroblastoma cells were investigated using the colorimetric alamar blue assay, which revealed significant effects on cell viability with an unequivocally structure–toxicity relationship. Finally, docking and molecular simulation studies were used to determine the H3R binding form, which will allow us to further modify the compounds to establish a robust structure-activity relationship and find a lead compound with therapeutic utility in neurodegenerative diseases.
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    Fluorescence properties of aurone derivatives: an experimental and theoretical study with some preliminary biological applications
    (2017) Espinosa Bustos, Christian Marcelo; Cortes Arriagada, Diego; Soto Arriaza, Marco; Robinson Duggon, José Luis; Pizarro, Nancy; Cabrera Caballero, Alan Raúl; Fuentealba Patiño, Denis Alberto; Salas Sánchez, Cristián Osvaldo
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    Hepatoprotective species from the Chilean medicinal flora : Junellia spathulata (Verbenaceae)
    (2021) Bridi, Raquel; Lino von Poser, G.; Gómez, Miguel; Andía Kohnenkampf, Marcelo Edgardo; Oyarzún Isamitt, Juan Esteban; Núñez, P.; Vasquez Arias, A. J.; Espinosa Bustos, Christian Marcelo
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    Nature-inspired pyrrolo[2,3-d]pyrimidines targeting the histamine H-3 receptor
    (2019) Frank, A.; Meza-Arriagada, F.; Salas Sánchez, Cristián Osvaldo; Espinosa Bustos, Christian Marcelo; Stark, H.
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    New 2,6,9-trisubstituted purine derivatives as Bcr-Abl and Btk inhibitors and as promising agents against leukemia
    (2020) Bertrand, J; Dostalova, H; Krystof, V; Jorda, R; Castro, A; Mella, J; Espinosa Bustos, Christian Marcelo; Zárate Méndez, Ana María; Salas Sánchez, Cristián Osvaldo
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    New aryloxy-quinone derivatives as potential anti-Chagasic agents : synthesis, trypanosomicidal activity, electrochemical properties, pharmacophore elucidation and 3D-QSAR analysis
    (2015) Vázquez, K.; Espinosa Bustos, Christian Marcelo; Soto, J.; Tapia, R.; Varela, J.; Birriel, E.; Segura Segura, Rodrigo; Pizarro, J.; Cerecetto, H.; González, M.; Paulino, M.; Salas, C.
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    New aryloxy-quinone derivatives with promising activity on Trypanosoma cruzi
    (2020) Espinosa Bustos, Christian Marcelo; Vazquez, K; Varela, J; Cerecetto, H; Paulino, M; Segura, R; Pizarro, J; Vera, B; Gonzalez, M; Zárate Méndez, Ana María; Salas, CO
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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 lead elements for histamine H3 receptor ligands in the pyrrolo[2,3-d]pyrimidine class
    (2018) Espinosa Bustos, Christian Marcelo; Frank, Annika; Arancibia Opazo, Sandra; Salas Sánchez, Cristián Osvaldo; Fierro Huerta, Angélica; Stark, Holger
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    Supramolecular Control on the Reactivity of New Quinolin-2(1h)-one derivatives Induced by Micellar systems
    (2025) Quintero Faúndez, Guillermo Esteban; Aliaga Miranda, Margarita Elly; Espinosa Bustos, Christian Marcelo; Pontificia Universidad Católica de Chile. Facultad de Química y de Farmacia
    Six new quinolin-2(1H)-one derivatives (E)-6-methoxy-1-methyl-3-(2-(3-methyl-4-nitroisoxazol-5-yl)vinyl)quinolin-2(1H)-one (MQI), 7-(diethylamino)quinolin-2(1H)-one-3-carbaldehyde (DQD1), 7-(diethylamino)-1-methylquinolin-2(1H)-one-3-carbaldehyde (DQD2), (E)-7-(diethylamino)-3-(3-(3-(4-nitrophenyl)-3-oxoprop-1-en-1-yl)-1-methylquinolin-2(1H)-one (DQD3), (E)-7-(diethylamino)-3-(3-(4-fluorophenyl)-3-oxoprop 1-en-1-yl)-1-methylquinolin-2(1H)-one (DQCh) and (E) 7(Diethylamino)-1-methyl-3-(2-(3-methyl-4-nitroisoxazol-5-yl)vinyl)quinolin-2(1H)-one (DQI) were synthesized and evaluated as colorimetric and fluorescent probes for bisulfite (HSO3) in aqueous micellar solutions. The compound MQI, designed as a Michael acceptor, showed low water solubility but significantly enhanced reactivity toward HSO3 in aqueous cationic micellar solution of cetyltrimethylammonium bromide (CTABr), with rate constants up to 200-fold higher than in zwitterionic systems, such as 3-(N,N-dimethyltetradecylammonium) propanesulfonate (SB3-14). On the other hand, DQD1-3, DQCh, and DQI were developed to improve the fluorescence response of quinoline-2(1H)-one ring. Notably, DQI displayed rare inverse solvatofluorochromism, dependent on solvent polarity, making it only the second reported case of this behavior in organic dyes to date. While DQD3 did not exhibit the appropriate photophysical or reactivity criteria due to the presence of both E/Z isomers, the other derivatives demonstrated the presence of only the E isomer (valid for DQCh and DQI), promising behavior in micellar systems, with binding constants (Ks) in the range of 103−106 M−1. Photophysical studies in water and micellar environments revealed that DQCh had the highest fluorescence quantum yield (𝜙𝑓) and excellent selectivity for HSO3 over other anions and biothiols. Complementarily, DQCh was testedin real sample analysis (white wine samples) with good results, also DFT calculations confirmed the adequate reactivity of the double-bound C-C ,-unsatured. On the other hand, DQI showed a low fluorescence and exhibited fast and selective “turn-off” responses to HSO3 and hypochlorite (ClO). Its reaction was supported by NMR analysis of Michael adduct formation. Overall, this study introduces new quinolin-2(1H)-one-based platforms for selective HSO3 −and/or ClO− sensing, highlighting the importance of aqueous micellar medium in tuning chemical reactivity and fluorescence properties. The findings contribute to developing functional probes for environmental and food analysis in an aqueous micellar solution, avoiding toxic organic solvents.
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    Synthesis and biological characterization of new aryloxyindole-4,9-diones as potent trypanosomicidal agents
    (2014) Tapia Apati, Ricardo; Salas Sánchez, Cristián Osvaldo; Vazquez, K.; Espinosa Bustos, Christian Marcelo; Soto Delgado, J.; Varela, J.; Birriel, E.; Cerecetto, H.; González, M.; Paulino, M.