Examinando por Autor "Alderete, Joel B."
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Ítem Chlorin e6-Conjugated Mesoporous Titania Nanorods as Potential Nanoplatform for Photo-Chemotherapy(Multidisciplinary Digital Publishing Institute (MDPI), 2024-06) Vélez-Peña, Estefanía; Jiménez, Verónica A.; Manzo-Merino, Joaquín; Alderete, Joel B.; Campos, Cristian H.Photodynamic therapy (PDT) has developed as an efficient strategy for cancer treatment. PDT involves the production of reactive oxygen species (ROS) by light irradiation after activating a photosensitizer (PS) in the presence of O2. PS-coupled nanomaterials offer additional advantages, as they can merge the effects of PDT with conventional enabling-combined photo-chemotherapeutics effects. In this work, mesoporous titania nanorods were surface-immobilized with Chlorin e6 (Ce6) conjugated through 3-(aminopropyl)-trimethoxysilane as a coupling agent. The mesoporous nanorods act as nano vehicles for doxorubicin delivery, and the Ce6 provides a visible light-responsive production of ROS to induce PDT. The nanomaterials were characterized by XRD, DRS, FTIR, TGA, N2 adsorption–desorption isotherms at 77 K, and TEM. The obtained materials were tested for their singlet oxygen and hydroxyl radical generation capacity using fluorescence assays. In vitro cell viability experiments with HeLa cells showed that the prepared materials are not cytotoxic in the dark, and that they exhibit photodynamic activity when irradiated with LED light (150 W m−2). Drug-loading experiments with doxorubicin (DOX) as a model chemotherapeutic drug showed that the nanostructures efficiently encapsulated DOX. The DOX-nanomaterial formulations show chemo-cytotoxic effects on Hela cells. Combined photo-chemotoxicity experiments show enhanced effects on HeLa cell viability, indicating that the conjugated nanorods are promising for use in combined therapy driven by LED light irradiation.Ítem Comprehensive analysis of crystal structure, spectroscopic properties, quantum chemical insights, and molecular docking studies of two pyrazolopyridine compounds: potential anticancer agents(Royal Society of Chemistry, 2023-11) Polo-Cuadrado, Efraín; López-Cuellar, Lorena; Acosta-Quiroga, Karen; Rojas-Peña, Cristian; Brito, Iván; Cisterna, Jonathan; Trilleras, Jorge; Alderete, Joel B.; Duarte, Yorley; Gutiérrez, MargaritaIn this study, two pyrazolo[3,4-b]pyridine derivatives (4a and 4b) were grown using a slow evaporation solution growth technique and characterized by FT-IR, HRMS, 1H/13C NMR spectroscopy, and X-ray crystallography. The 4a and 4b structures crystallized in monoclinic and triclinic systems with space groups P21/n and P1̄, respectively. Theoretical calculations were performed at the DFT/B3LYP level for the optimized geometries. The results were in excellent agreement with the experimental data (spectroscopic and XRD). This investigation encompasses molecular modeling studies including Hirshfeld surface analysis, energy framework calculations, and frontier molecular orbital analysis. Intermolecular interactions within the crystal structures of the compounds were explored through Hirshfeld surface analysis, which revealed the notable presence of hydrogen bonding and hydrophobic interactions. This insight provides valuable information on the structural stability and potential solubility characteristics of these compounds. The research was extended to docking analysis with eight distinct kinases (BRAF, HER2, CSF1R, MEK2, PDGFRA, JAK, AKT1, and AKT2). The results of this analysis demonstrate that both 4a and 4b interact effectively with the kinase-binding sites through a combination of hydrophobic interactions and hydrogen bonding. Compound 4a had the best affinity for proteins; this is related to the fact that the compound is not rigid and has a small size, allowing it to sit well at any binding site. This study contributes to the advancement of kinase inhibitor research and offers potential avenues for the development of new therapeutic agents for cancer treatment. © 2023 The Royal Society of Chemistry.Ítem Molecular modeling simulation studies reveal new potential inhibitors against HPV E6 protein(PLoS ONE, 2019-03) Ricci-López, Joel; Vidal-Limon, Abraham; Zunñiga, Matías; Jiménez, Verónica A.; Alderete, Joel B.; Brizuela, Carlos A.; Aguila, SergioHigh-risk strains of human papillomavirus (HPV) have been identified as the etiologic agent of some anogenital tract, head, and neck cancers. Although prophylactic HPV vaccines have been approved; it is still necessary a drug-based treatment against the infection and its oncogenic effects. The E6 oncoprotein is one of the most studied therapeutic targets of HPV, it has been identified as a key factor in cell immortalization and tumor progression in HPV-positive cells. E6 can promote the degradation of p53, a tumor suppressor protein, through the interaction with the cellular ubiquitin ligase E6AP. Therefore, preventing the formation of the E6-E6AP complex is one of the main strategies to inhibit the viability and proliferation of infected cells. Herein, we propose an in silico pipeline to identify small-molecule inhibitors of the E6-E6AP interaction. Virtual screening was carried out by predicting the ADME properties of the molecules and performing ensemble-based docking simulations to E6 protein followed by binding free energy estimation through MM/PB(GB)SA methods. Finally, the top-three compounds were selected, and their stability in the E6 docked complex and their effect in the inhibition of the E6-E6AP interaction was corroborated by molecular dynamics simulation. Therefore, this pipeline and the identified molecules represent a new starting point in the development of anti-HPV drugs.Ítem PAMAM-grafted TiO2 nanotubes as novel versatile materials for drug delivery applications(Elsevier Ltd, 2016-08) Torres, Cecilia C.; Campos, Cristian H.; Diáz, Carola; Jiménez, Verónica A.; Vidal, Felipe; Guzmán, Leonardo; Alderete, Joel B.PAMAM-grafted TiO2 nanotubes (PAMAM-TiO2NT) have been synthesized and evaluated as new drug nanocarriers, using curcumin (CUR), methotrexate (MTX), and silibinin (SIL) as model therapeutic compounds. TiO2NT were surface-modified using a silane coupling agent and subsequently conjugated with PAMAM dendrimer of the third generation. The characterization of PAMAM-TiO2NT nanomaterials was performed by FTIR, TEM, N2 adsorption-desorption isotherms, XRD, and TGA techniques, which accounted for a 2.6 wt.% of PAMAM grafting in the prepared materials. The drug loading capacity, drug release properties, and cytotoxicity of PAMAM-TiO2NT showed a significant improvement compared to pristine TiO2NT, thus revealing the promising properties of these new materials for drug delivery purposes. © 2016 Elsevier B.V. All rights reserved.Ítem Regioselective cyclocondensations with thiobarbituric acid: spirocyclic and azocine products, X-ray characterization, and antioxidant evaluation(Royal Society of Chemistry, 0025-03) Polo-Cuadrado, Efraín; Acosta-Quiroga, Karen; Rojas-Peña, Cristian; Rodriguez-Nuñez, Yeray A; Blanco-Acuña, Edgard Fabián; Lopez, Jhon J.; Brito, Iván; Cisterna, Jonathan; Alderete, Joel B.; Gutiérrez, MargaritaMulticomponent cyclocondensations of 5-amino-3-methyl-1-phenyl-1H-pyrazole (AMPZ), thiobarbituric acid, and p-formaldehyde under conventional thermal heating or ultrasonic irradiation were studied. Treatment of the reaction mixture in ethanol in an ultrasonic bath for 3 h produced azocine compound 4b, while the same mixture in ethanol under reflux conditions for 15 h produced spiro compound 4a. This work encompasses intricate experimental details, X-ray diffraction measurements, and multifaceted computational analyses employing methods such as the density functional theory and Hirshfeld surface analysis. Crystallographic investigations revealed the molecular structure of the compound and clarified its interactions involving hydrogen bonds and weak intermolecular forces. This article describes the synthesis and characterization of a novel spirocyclic compound. The study also evaluated the antioxidant potential in vitro using the DPPH and ABTS methods. The results showed that these compounds showed the best free radical scavenging ability, even in very small amounts, and that even at very low concentrations, these compounds showed excellent radical scavenging potential. Surprisingly, these compounds exhibited strong (ABTS+) radical scavenging activities, mainly attributed to the HAT mechanism, indicating their potential as therapeutic agents. Facile multipurpose, three-component selective procedures for new spiroheterocycles have been proposed, presenting intriguing perspectives in the field of medicine, particularly in the field of antioxidants. The geometric values of the computationally optimized structure were calculated using the density functional theory in LC-BLYP/6-31(d), aligned with the X-ray diffraction data, reinforcing the precision of our findings. © 2025 The Royal Society of ChemistryÍtem Visible light-activated mesoporous black titania nanorods for enhanced chemo-photodynamic cancer therapy(Editions de Sante, 2025-04) Vélez-Peña, Estefanía; Jiménez, Verónica A.; Manzo-Merino, Joaquín; Melin, Victoria; Contreras, David; Alderete, Joel B.; Campos, Cristian H.Developing photoactive nanomaterials with drug-encapsulating properties is a relevant task for dual therapy applications aimed at overcoming the current limitations of conventional cancer treatments. In this work, we report the synthesis and evaluation of mesoporous black titania nanorods as novel visible-light responsive platforms for dual chemo-phototherapy. Nanorods were obtained by hydrothermal synthesis and photo-sensitized by titanium reduction via thermal decomposition of sodium borohydride at 400 °C under an argon atmosphere. The materials were characterized by X-ray diffraction, transmission electron microscopy, N2 adsorption-desorption isotherms, X-ray photoelectron spectroscopy, electron paramagnetic resonance, and UV–vis diffuse reflectance spectroscopy. ROS generation experiments confirmed that aqueous dispersions of black titania nanorods produce hydroxyl radicals (HO•) under visible light LED irradiation (150 W m−2, 15 min). The materials exhibited moderate phototoxic activity against HeLa cells under visible light LED irradiation (150 W m−2, 15 min) with cell viabilities ∼70 % at dispersion concentrations of 300 μg mL−1, while no cytotoxic effects were observed in dark incubation conditions. Black titania nanorods efficiently encapsulated doxorubicin and released the drug in quantities suitable to exert chemotoxic effects against HeLa cells in the dark, with cell viabilities of ∼60 % at 500 μg mL−1 dispersion concentrations and 24 h of incubation. Doxorubicin-loaded nanorods were evaluated in dual chemo-phototherapy experiments consisting of 12 h of dark incubation, 15 min of visible light LED irradiation, and 12 h of post-irradiation dark incubation. Our experiments showed a marked potentiation of antiproliferative effects compared with individual chemo or phototoxicity experiments, with cell viabilities ∼30 % at dispersion concentrations of 400 μg mL−1. Our findings highlight the potential of black titania nanorods as intrinsically photoactive materials with drug-encapsulating properties for dual chemo-phototherapy applications.