http://hdl.handle.net/10366/123990 2026-04-23T09:08:32Z 2026-04-23T09:08:32Z Hernández García, Ángela Patricia Díez, Paula García García, Pablo Anselmo Pérez Andrés, Martín Veselinova Marinova, Anzhela García Jambrina, Pablo San Feliciano Martín, Arturo Díez Martín, David Fuentes García, Manuel Castro González, María Ángeles http://hdl.handle.net/10366/156817 2025-04-30T20:45:38Z 2023-01-01T00:00:00Z

[EN]New lignohydroquinone conjugates (L-HQs) were designed and synthesized using the hybridization strategy, and evaluated as cytotoxics against several cancer cell lines. The L-HQs were obtained from the natural product podophyllotoxin and some semisynthetic terpenylnaphthohydroquinones, prepared from natural terpenoids. Both entities of the conjugates were connected through different aliphatic or aromatic linkers. Among the evaluated hybrids, the L-HQ with the aromatic spacer clearly displayed the in vitro dual cytotoxic effect derived from each starting component, retaining the selectivity and showing a high cytotoxicity at short (24 h) and long (72 h) incubation times (4.12 and 0.0450 µM, respectively) against colorectal cancer cells. In addition, the cell cycle blockade observed by flow cytometry studies, molecular dynamics, and tubulin interaction studies demonstrated the interest of this kind of hybrids, which docked adequately into the colchicine binding site of tubulin despite their large size. These results prove the validity of the hybridization strategy and encourage further research on non-lactonic cyclolignans.

2023-01-01T00:00:00Z Arias-Hidalgo, Carlota Juanes Velasco, Pablo Landeira Viñuela, Alicia García-Vaquero, Marina L. Montalvillo Álvarez, Enrique Góngora Fernández, Rafael Hernández García, Ángela Patricia Fuentes García, Manuel http://hdl.handle.net/10366/155216 2025-04-30T20:45:38Z 2022-01-01T00:00:00Z

[EN]In single-cell analysis, biological variability can be attributed to individual cells, their specific state, and the ability to respond to external stimuli, which are determined by protein abundance and their relative alterations. Mass spectrometry (MS)-based proteomics (e.g., SCoPE-MS and SCoPE2) can be used as a non-targeted method to detect molecules across hundreds of individual cells. To achieve high-throughput investigation, novel approaches in Single-Cell Proteomics (SCP) are needed to identify and quantify proteins as accurately as possible. Controlling sample preparation prior to LC-MS analysis is critical, as it influences sensitivity, robustness, and reproducibility. Several nanotechnological approaches have been developed for the removal of cellular debris, salts, and detergents, and to facilitate systematic sample processing at the nano- and microfluidic scale. In addition, nanotechnology has enabled high-throughput proteomics analysis, which have required the improvement of software tools, such as DART-ID or DO-MS, which are also fundamental for addressing key biological questions. Single-cell proteomics has many applications in nanomedicine and biomedical research, including advanced cancer immunotherapies or biomarker characterization, among others; and novel methods allow the quantification of more than a thousand proteins while analyzing hundreds of single cells.

2022-01-01T00:00:00Z Hernández García, Ángela Patricia Micaelo, Ania Piñol, Rafael García-Vaquero, Marina L. Aramayona, José J. Criado, Julio J. Rodriguez, Emilio Sánchez Gallego, José Ignacio Landeira Viñuela, Alicia Juanes Velasco, Pablo Díez, Paula Góngora Fernández, Rafael Jara-Acevedo, Ricardo Orfao de Matos Correia e Vale, José Alberto Miana-Mena, Javier Muñoz, María Jesús Villanueva, Sergio Millán, Ángel Fuentes García, Manuel http://hdl.handle.net/10366/155213 2025-04-30T20:45:39Z 2022-01-01T00:00:00Z

[EN]Background: Nowadays, nanoparticles (NPs) have evolved as multifunctional systems combining diferent custom anchorages which opens a wide range of applications in biomedical research. Thus, their pharmacological involve‑ ments require more comprehensive analysis and novel nanodrugs should be characterized by both chemically and biological point of view. Within the wide variety of biocompatible nanosystems, iron oxide nanoparticles (IONPs) present mostly of the required features which make them suitable for multifunctional NPs with many biopharmaceu‑ tical applications. Results: Cisplatin-IONPs and diferent functionalization stages have been broadly evaluated. The potential applica‑ tion of these nanodrugs in onco-therapies has been assessed by studying in vitro biocompatibility (interactions with environment) by proteomics characterization the determination of protein corona in diferent proximal fuids (human plasma, rabbit plasma and fetal bovine serum),. Moreover, protein labeling and LC–MS/MS analysis provided more than 4000 proteins de novo synthetized as consequence of the nanodrugs presence defending cell signaling in dif‑ ferent tumor cell types (data available via ProteomeXchanges with identifed PXD026615). Further in vivo studies have provided a more integrative view of the biopharmaceutical perspectives of IONPs. Conclusions: Pharmacological proteomic profle diferent behavior between species and diferent afnity of protein coating layers (soft and hard corona). Also, intracellular signaling exposed diferences between tumor cell lines

2022-01-01T00:00:00Z Juanes Velasco, Pablo Landeira-Viñuela, Alicia García-Vaquero, Marina L. Lécrevisse, Quentin André Herrero, Raquel Ferruelo, Antonio Góngora Fernández, Rafael Corrales, Fernando Rivas Sanz, Javier de las Lorente, Jose A. Hernández García, Ángela Patricia Fuentes García, Manuel http://hdl.handle.net/10366/155210 2025-04-30T20:45:39Z 2022-01-01T00:00:00Z

[EN]Acute respiratory distress syndrome (ARDS) is a severe pulmonary disease, which is one of the major complications in COVID-19 patients. Dysregulation of the immune system and imbalances in cytokine release and immune cell activation are involved in SARS-CoV-2 infection. Here, the inflammatory, antigen, and auto-immune profile of patients presenting COVID-19-associated severe ARDS has been analyzed using functional proteomics approaches. Both, innate and humoral responses have been characterized through acute-phase protein network and auto-antibody signature. Severity and sepsis by SARS-CoV-2 emerged to be correlated with auto-immune profiles of patients and define their clinical progression, which could provide novel perspectives in therapeutics development and biomarkers of COVID-19 patients. Humoral response in COVID-19 patients’ profile separates with significant differences patients with or without ARDS. Furthermore, we found that this profile can be correlated with COVID-19 severity and results more common in elderly patients.

2022-01-01T00:00:00Z Landeira-Viñuela, Alicia Arias-Hidalgo, Carlota Juanes Velasco, Pablo Alcoceba Sánchez, Miguel Navarro Bailón, Almudena Pedreira, Carlos Eduardo Lécrevisse, Quentin André Díaz Muñoz, Laura Sánchez Santos, José Manuel Hernández García, Ángela Patricia García-Vaquero, Marina L. Góngora Fernández, Rafael Rivas Sanz, Javier de las González, Marcos Orfao de Matos Correia e Vale, José Alberto Fuentes García, Manuel http://hdl.handle.net/10366/155202 2025-04-30T20:45:40Z 2022-01-01T00:00:00Z

[EN]Chronic lymphocytic leukemia (CLL) is a lymphoid neoplasm characterized by the accumulation of mature B cells. The diagnosis is established by the detection of monoclonal B lymphocytes in peripheral blood, even in early stages [monoclonal B-cell lymphocytosis (MBLhi)], and its clinical course is highly heterogeneous. In fact, there are well-characterized multiple prognostic factors that are also related to the observed genetic heterogenicity, such as immunoglobulin heavy chain variable region (IGHV) mutational status, del17p, and TP53 mutations, among others. Moreover, a dysregulation of the immune system (innate and adaptive immunity) has been observed in CLL patients, with strong impact on immune surveillance and consequently on the onset, evolution, and therapy response. In addition, the tumor microenvironment is highly complex and heterogeneous (i.e., matrix, fibroblast, endothelial cells, and immune cells), playing a critical role in the evolution of CLL. In this study, a quantitative profile of 103 proteins (cytokines, chemokines, growth/regulatory factors, immune checkpoints, and soluble receptors) in 67 serum samples (57 CLL and 10 MBLhi) has been systematically evaluated. Also, differential profiles of soluble immune factors that discriminate between MBLhi and CLL (sCD47, sCD27, sTIMD-4, sIL-2R, and sULBP-1), disease progression (sCD48, sCD27, sArginase-1, sLAG-3, IL-4, and sIL-2R), or among profiles correlated with other prognostic factors, such as IGHV mutational status (CXCL11/I-TAC, CXCL10/IP-10, sHEVM, and sLAG-3), were deciphered. These results pave the way to explore the role of soluble immune checkpoints as a promising source of biomarkers in CLL, to provide novel insights into the immune suppression process and/or dysfunction, mostly on T cells, in combination with cellular balance disruption and microenvironment polarization leading to tumor escape.

2022-01-01T00:00:00Z Hernández García, Ángela Patricia Juanes Velasco, Pablo Landeira-Viñuela, Alicia Bareke, Halin Montalvillo Álvarez, Enrique Góngora Fernández, Rafael Fuentes García, Manuel http://hdl.handle.net/10366/155197 2025-04-30T20:45:40Z 2021-01-01T00:00:00Z

[EN]Immunogenic cell death (ICD) elicited by cancer therapy reshapes the tumor immune microenvironment. A long-term adaptative immune response can be initiated by modulating cell death by therapeutic approaches. Here, the major hallmarks of ICD, endoplasmic reticulum (ER) stress, and damage-associated molecular patterns (DAMPs) are correlated with ICD inducers used in clinical practice to enhance antitumoral activity by suppressing tumor immune evasion. Approaches to monitoring the ICD triggered by antitumoral therapeutics in the tumor microenvironment (TME) and novel perspective in this immune system strategy are also reviewed to give an overview of the relevance of ICD in cancer treatment.

2021-01-01T00:00:00Z Hernández García, Ángela Patricia Díez, Paula García García, Pablo Anselmo Miguel del Corral, José M. Pérez Andrés, Martín Díez Martín, David San Feliciano Martín, Arturo Fuentes García, Manuel Castro González, María Ángeles http://hdl.handle.net/10366/155195 2025-04-30T20:45:40Z 2018-03-08T00:00:00Z

[EN]A new family of molecular hybrids, between cyclolignans related to podophyllic aldehyde and several diterpenylnaphthohydroquinones (DNHQ), was prepared and its biological activity evaluated in several human solid tumor cell lines, which are representative of the most prevalent solid tumors in the Western world. Both cyclolignan and quinone fragments were linked through aliphatic or aromatic spacers. The new hybrid family was evaluated for its cytotoxicity, and it was found that the hybrids were several times more potent against the osteosarcoma cell line MG-63 than against MCF-7 and HT-29 cell lines. The presence of an aromatic ring in the linker gave the most potent and selective agent, improving the cytotoxicity of the parent compounds. Cell cycle studies demonstrated that this hybrid induces a strong and rapid apoptotic effect and arrests cells at the G2/M phase of the cell cycle, in the same way that the parent compound podophyllic aldehyde does.

2018-03-08T00:00:00Z Hernández, Ángela P. Chamorro, Pablo Rodríguez, Mª Lucena Miguel del Corral, José M. García García, Pablo Anselmo Francesch, Andrés San Feliciano, Arturo Castro, Mª Ángeles http://hdl.handle.net/10366/154894 2025-04-30T20:45:41Z 2021-01-01T00:00:00Z

[EN]Terpenylquinones are mixed biogenesis primary or secondary metabolites widespread in Nature with many biological activities, including the antineoplastic cytotoxicity, that have inspired this work. Here, we present a cytotoxic structure-activity relationship of several diterpenylhydroquinone (DTHQ) derivatives, obtained from the natural labdane diterpenoid myrceocommunic acid used as starting material. Different structural modifications, that changed the functionality and stereochemistry of the decalin, have been implemented on the bicyclic core through epoxidation, ozonolysis or decarboxylation, and through induction of biomimetic breaks and rearrangements of the diterpene skeleton. All the isomers generated were completely characterized by spectroscopic procedures. The resulting compounds have been tested in vitro on cultured cancer cells, showing their relevant antineoplastic cytotoxicity, with GI50 values in the μM and sub-μM range. The rearranged compound 8 showed the best cytotoxic results, with GI50 at the submicromolar range, retaining the cytotoxicity level of the parent compounds. In this report, the versatility of the labdane skeleton for chemical transformation and the interest to continue using structural modifications to obtain new bioactive compounds are demonstrated.

2021-01-01T00:00:00Z Martín Garrido, Narciso Rubia, Alfonso G. Nieto García, Carlos Tomás Díez Martín, David http://hdl.handle.net/10366/124098 2025-04-30T20:45:42Z 2010-01-01T00:00:00Z

[ES]Se describe la adición asimétrica de Michael de (R)-N-bencil-N-alfa- metilbencilamiduro de litio al diester ortogonalmente sustituido (2E,7E)-nonadienedioato de hidrogeno y metilo para obtener un aducto de monoadición que por posterior manipulación del doble enlace remanente conduce a una síntesis eficaz de ácido (R)-homopipecolico y monomeros utiles en la sintesis de ácidos péptido nucleicos.

2010-01-01T00:00:00Z Urones, Julio G. Marcos, Isidro S. Garrido, Narciso M. Basabe Barcala, María Pilar Sanfeliciano, Sonia G. Coca, Raquel Díez, David http://hdl.handle.net/10366/124081 2025-04-30T20:45:42Z 1998-12-01T00:00:00Z

[ES] Obtención de análogos de isosorbide en un solo paso a partir de sulfonilbutadienos.

1998-12-01T00:00:00Z Díez, David Núñez, M. G. Beneitez, A. Fernández Moro, Rosalina Marcos, I. S. Basabe Barcala, María Pilar Broughton, H. B. Urones, Julio G. http://hdl.handle.net/10366/124072 2025-04-30T20:45:42Z 2009-01-01T00:00:00Z

[ES] Se describe por primera vez la síntesis de un tetrahidropirano quiral mediante organocatálisis.

2009-01-01T00:00:00Z Urones, Julio G. Marcos, Isidro S. Garrido, Narciso M. Basabe Barcala, María Pilar Bastida, Angel J. Sanfeliciano, Sonia G. Díez, David Goodman, J. M. http://hdl.handle.net/10366/124071 2025-04-30T20:45:42Z 1998-12-01T00:00:00Z

[ES]Reactividad de sulfonas para la obtención de sistemas dienicos.

1998-12-01T00:00:00Z Marcos, Isidro S. Fernández Moro, Rosalina Costales González, María Isabel Basabe Barcala, María Pilar Díez, David http://hdl.handle.net/10366/124025 2025-04-30T20:45:41Z 2013-10-31T00:00:00Z

The natural product sesquiterpenyl indoles are structural hybrids fromfarnesyl pyrophosphate and tryptophan or its precursors, often with unusual and complex structural features,many of themwith interesting biological activities. In this review the compounds of this class known until now are classified, a biosynthetic approach of each group is proposed and a review of the synthesis or synthetic approaches is communicated

2013-10-31T00:00:00Z