Examinando por Autor "Delpiccolo, Carina M. L."

Mostrando 1 - 7 de 7
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    A penicillin derivative exerts an anti-metastatic activity in melanoma cells through the downregulation of integrin αvβ3 and Wnt/β-Catenin pathway
    (Frontiers Media, 2020-02-25) Barrionuevo, Elizabeth; Cayrol, María Florencia; Cremaschi, Graciela Alicia; Cornier, Patricia Griselda; Boggián, Dora Bernarda; Delpiccolo, Carina M. L.; Mata, Ernesto Gabino; Roguin, Leonor P.; Blank, Viviana C.
    The synthetic triazolylpeptidyl penicillin derivative, named TAP7f, has been previously characterized as an effective antitumor agent in vitro and in vivo against B16-F0 melanoma cells. In this study, we investigated the anti-metastatic potential of this compound on highly metastatic murine B16-F10 and human A375 melanoma cells. We found that TAP7f inhibited cell adhesion, migration and invasion in a dose-dependent manner. Additionally, we demonstrated that TAP7f downregulated integrin αvβ3 expression and Wnt/β-catenin pathway, a signaling cascade commonly related to tumor invasion and metastasis. Thus, TAP7f reduced both the enzymatic activity and the expression levels of matrix-metalloproteinases-2 and -9 in a time dependent manner. Moreover, TAP7f inhibited the expression of the transcription factor Snail and the mesenchymal markers vimentin, and N-cadherin, and up-regulated the expression of the epithelial marker E-cadherin, suggesting that the penicillin derivative affects epithelial–mesenchymal transition. Results obtained in vitro were supported by those obtained in a B16-F10-bearing mice metastatic model, that showed a significant TAP7f inhibition of lung metastasis. These findings suggest the potential of TAP7f as a chemotherapeutic agent for the treatment of metastatic melanoma.
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    Antitumor activity of new chemicalcompounds in triple negative mammaryadenocarcinoma models
    (Future Science, 2020-02-23) Giolito, María V.; Camacho, Cristián Matías; Martínez Amezaga, Maitena; Traficante, Carla Inés; Giordano, Rocío A.; Cornier, Patricia Griselda; Mata, Ernesto Gabino; Delpiccolo, Carina M. L.; Boggián, Dora Bernarda; Del Giúdice, Antonela; Mainetti, Leandro; Scharovsky, Olga G.; Rozados, Viviana; Rico, María José
    Aim: According to the need for the development of new anticancer agents, we have synthetized novel bioactive compounds and aimed to determine their antitumor action. Materials & methods: We describe in vitro studies evaluating the effect of 35 novel chemical compounds on two triple negative murine mammary adenocarcinoma tumors. Results & conclusion: Three compounds were selected because of their high antitumor activity and their low toxicity to normal cells. Their effect on tumor cells apoptosis, clonogenicity and migratory capacity, were determined. We found that the selected compounds showed inhibition of viability and clonogenic capacity, and promotion of apoptosis. They also decreased the migratory capacity of tumor cells. The results obtained suggest the likely hood of their future use as antitumor and/or antimetastatic agents. Lay abstract: In spite of the important progress achieved in cancer therapeutics, the percentage of people dying because of cancer is still high. Hence, we need to develop new, effective and nontoxic anticancer agents. We synthetized novel compounds and tested their antitumor effect and toxicity, in order to choose those that are effective and do not affect normal cells and therefore, are suitable for human cancer therapies. We selected three out of 35 compounds that show high antitumor action and low toxicity. Also, we studied the mechanisms by which that effect was achieved. Our next goal is to develop experiments with animals in order to have preclinical data that, hopefully, will lead to the clinical use of one or more of the selected compounds.
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    Desarrollo de métodos one-pot a partir de N-tosiltriazoles hacia la generación de compuestos de interés con diversidad y complejidad estructura
    (2024-12-18) Bianchini, Maira Ángeles; Delpiccolo, Carina M. L.; Permingeat Squizatto, Caterina: Directora Asistente
    El arreglo estructural de pirrolidinas se encuentra presente en un incontable número de productos naturales y sintéticos con actividad biológica. Basado en avances previos del grupo de trabajo, que establecieron un protocolo simple y eficiente para la modulación de Nsulfoniltriazoles, hacia la obtención de diferentes heterociclos bajo catálisis de [Rh(II)], este trabajo aborda la optimización de una estrategia one-pot hacia la síntesis de Nsulfonilpirrolidinas 5, integrando la transanulación de N-sulfoniltriazoles 1 con alquenos 2 bajo catálisis de [Rh(II)], seguido de un reordenamiento Cloke-Wilson y reducción mediante un sistema triisopropilsilano/I2. Se evaluaron diferentes condiciones y sistemas reductores logrando una metodología óptima hacia la conversión eficiente de pirrolidinas 5. Además, se exploró el alcance de la reacción mediante un análisis de los sustratos compatibles, identificando los grupos funcionales y sustratos más eficientes para el desarrollo metodológico. Esta estrategia one-pot demostró ser práctica y eficiente, ya que elimina la necesidad de purificar y aislar intermediarios, reduciendo significativamente el tiempo y los recursos requeridos en el proceso. Estos hallazgos destacan la utilidad de esta metodología para la síntesis eficiente de pirrolidinas, contribuyendo a ampliar las metodologías sintéticas ambientalmente responsable.
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    Diseño de metodologías de síntesis orientadas a la diversidad para la obtención de compuestos biológicos interesantes
    (2020) Prada Gori, Denis Nihuel; Delpiccolo, Carina M. L.
    La química orgánica juega un rol fundamental en el progreso del conocimiento científico y junto con la química medicinal, es especialmente importante para el desarrollo de los procesos relacionados con el estudio de funciones biológicas y para la búsqueda de nuevos agentes terapéuticos. Su campo de acción se centra no sólo en descubrir, sino también en generar nuevos compuestos de interés biológico. Por estos motivos, disponer de metodologías sintéticas eficientes constituye uno de los objetivos básicos de la investigación científica en el área. Hoy en día las demandas son muchas, por lo que es deseable disponer de diversas metodologías y lograr aplicarlas según conveniencia. Dentro de las exigencias actuales podemos mencionar: la accesibilidad rápida a moléculas diversas para explorar zonas no cubiertas del espacio químico;1 disponer de metodologías rápidas que eviten la producción de residuos tóxicos, empleando procedimientos “amigables” con el medio ambiente, la incorporación de nuevas tecnologías, tales como reacciones asistidas por microondas, tratamiento ultrasónico, procesos en microreactores, líquidos iónicos, geles y reacciones en medios supercríticos, entre otros. Existen varios desarrollos que se han desarrollado y que le han dado ímpetu a la química orgánica para enfrentar los nuevos desafíos del progreso científico. Ejemplos de esto es, el uso de complejos de metales de transición, los cuales han demostrado ser muy útiles como catalizadores de diversas reacciones de síntesis en química orgánica. Particularmente la catálisis organometálica es una herramienta fundamental para la formación de enlaces carbono-carbono y carbono-heteroátomo (N, O, S), pasos claves para la construcción de moléculas complejas a partir de precursores simples. Una relativamente nueva estrategia logra satisfacer la necesidad de desarrollar grandes colecciones de moléculas pequeñas estructuralmente diversas, poblando distintas zonas del espacio químico, es la Síntesis Orientada a la Diversidad (Diversity-Oriented Synthesis, DOS).
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    Garbage in, garbage out: how reliable training data improved a virtual screening approach against SARS-CoV-2 MPro
    (Frontiers, 2023-06-22) Ruatta, Santiago M.; Prada Gori, Denis N.; Fló Díaz, Martín; Carlucci, Renzo; Medrán, Noelia Soledad; Labadie, Guillermo Roberto; Martínez Amezaga, Maitena; Delpiccolo, Carina M. L.; Mata, Ernesto Gabino; Talevi, Alan; Comini, Marcelo A.; Dr. Hilgenfeld, R. provide the MPro expression vector
    Introduction: The identification of chemical compounds that interfere with SARS-CoV-2 replication continues to be a priority in several academic and pharmaceutical laboratories. Computational tools and approaches have the power to integrate, process and analyze multiple data in a short time. However, these initiatives may yield unrealistic results if the applied models are not inferred from reliable data and the resulting predictions are not confirmed by experimental evidence. Methods: We undertook a drug discovery campaign against the essential major protease (MPro) from SARS-CoV-2, which relied on an in silico search strategy –performed in a large and diverse chemolibrary– complemented by experimental validation. The computational method comprises a recently reported ligand-based approach developed upon refinement/learning cycles, and structure-based approximations. Search models were applied to both retrospective (in silico) and prospective (experimentally confirmed) screening. Results: The first generation of ligand-based models were fed by data, which to a great extent, had not been published in peer-reviewed articles. The first screening campaign performed with 188 compounds (46 in silico hits and 100 analogues, and 40 unrelated compounds: flavonols and pyrazoles) yielded three hits against MPro (IC50 ≤ 25 μM): two analogues of in silico hits (one glycoside and one benzo-thiazol) and one flavonol. A second generation of ligand-based models was developed based on this negative information and newly published peer-reviewed data for MPro inhibitors. This led to 43 new hit candidates belonging to different chemical families. From 45 compounds (28 in silico hits and 17 related analogues) tested in the second screening campaign, eight inhibited MPro with IC50 = 0.12–20 μM and five of them also impaired the proliferation of SARS-CoV-2 in Vero cells (EC50 7–45 μM). Discussion: Our study provides an example of a virtuous loop between computational and experimental approaches applied to target-focused drug discovery against a major and global pathogen, reaffirming the well-known “garbage in, garbage out” machine learning principle.
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    Immobilized boronic acid for Suzuki–Miyaura coupling: application to the generation of pharmacologically relevant molecules
    (Royal Society of Chemistry, 2017-07-12) Martínez Amezaga, Maitena; Delpiccolo, Carina M. L.; Mata, Ernesto Gabino
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    Unprecedented multifunctionality of Grubbs and Hoveyda–Grubbs catalysts: competitive isomerization, hydrogenation, silylation and metathesis occurring in solution and on solid phase
    (MDPI, 2017-04-09) Martínez Amezaga, Maitena; Delpiccolo, Carina M. L.; Méndez, Luciana; Dragutan, Ileana; Dragutan, Valerian; Mata, Ernesto Gabino