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Mercedes Zurro

Mercedes Zurro De la Fuente

Senior Research Fellow

    • 2023: Profesor Ayudante Doctor, Universidad de Alcalá.
    • 2022-2023: Investigadora del programa Atracción de Talento modalidad 2 de la Comunidad de Madrid, Universidad de Alcalá.
    • 2021-2021: Investigadora postdoctoral en el grupo de Prof. Miquel A. Pericàs, ICIQ.
    • 2018-2020: Investigadora postdoctoral Ramón Areces en el grupo de Prof. Syuzanna Harutyunyan, Rijks Universiteit Groningen.
    • 2017-2018: Investigadora postdoctoral en el grupo de Prof. Luis Sánchez, UCM.
    • 2016: Investigadora predoctoral en el grupo de Prof. Dr. Olga García Mancheño, WWU Münster / Universität Regensburg. Dr. rer. nat. “Chiral triazole-based anion-binding catalysts for the asymmetric dearomatization of N-heteroarenes”
    • 2012: Máster en Química Orgánica, UCM.
    • 2011: Licenciatura en Química, UCM.
2022, Publicación

de-Lucio et al. Eur J Med Chem. 2022;227:113915. Pyridazino-pyrrolo-quinoxalinium salts as highly potent and selective leishmanicidal agents targeting trypanothione reductase.

Publicaciones > de-Lucio et al

Eur J Med Chem. 2022 Jan 5;227:113915. doi: 10.1016/j.ejmech.2021.113915. PubMed 34695777

Pyridazino-pyrrolo-quinoxalinium salts as highly potent and selective leishmanicidal agents targeting trypanothione reductase.

Héctor de Lucio1, a, Javier García-Marín2, 3, 4, b, Patricia Sánchez-Alonso5, c, Juan Carlos García-Soriano1, d, Miguel Ángel Toro1, e, Juan J Vaquero2, 3, 4, f, Federico Gago6, g, Ramón Alajarín2, 3, 4, h, Antonio Jiménez-Ruiz1, i

1. Departamento de Biología de Sistemas, Universidad de Alcalá, E-28805, Alcalá de Henares, Madrid, Spain. Electronic address:.  2. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28805, Alcalá de Henares, Madrid, Spain.  3. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) Ctra, Colmenar Viejo, km. 9100, 28034, Madrid, Spain.  4. Instituto de Investigación Química Andrés Manuel del Río (IQAR), Universidad de Alcalá, 28805, Alcalá de Henares, Madrid, Spain. Electronic address:.  5. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28805, Alcalá de Henares, Madrid, Spain. Electronic address:.  6. Área de Farmacología, Departamento de Ciencias Biomédicas, Unidad Asociada al IQM-CSIC, Universidad de Alcalá, E-28805, Alcalá de Henares, Madrid, Spain. Electronic address:.

a. hector.lucio@edu.uah.es  b. javier.garciamarin@uah.es  c. sanchezalonsopatricia@gmail.com  d. jcarlos.garcias@uah.es  e. migueltoro83@gmail.com  f. juanjose.vaquero@uah.es  g. federico.gago@uah.es  h. ramon.alajarin@uah.es  i. antonio.jimenez@uah.es

Keywords: Enzyme inhibitor; Leishmania; Pyridazino[2,3-a]pyrrolo[2,1-c]quinoxalinium; Trypanothione disulfide reductase

Abstract

Fifteen pyridazino-pyrrolo-quinoxalinium salts were synthesized and tested for their antiprotozoal activity against Leishmania infantum amastigotes. Eleven of them turned out to be leishmanicidal, with EC(50) values in the nanomolar range, and displayed low toxicity against the human THP-1 cell line. Selectivity indices for these compounds range from 10 to more than 1000. Compounds 3b and 3f behave as potent inhibitors of the oxidoreductase activity of the essential enzyme trypanothione disulfide reductase (TryR). Interestingly, binding of 3f is not affected by high trypanothione concentrations, as revealed by the noncompetitive pattern of inhibition observed when tested in the presence of increasing concentrations of this substrate. Furthermore, when analyzed at varying NADPH concentrations, the characteristic pattern of hyperbolic uncompetitive inhibition supports the view that binding of NADPH to TryR is a prerequisite for inhibitor-protein association. Similar to other TryR uncompetitive inhibitors for NADPH, 3f is responsible for TryR-dependent reduction of cytochrome c in a reaction that is typically inhibited by superoxide dismutase.

Noticias

Organización XVII SIJ-RSEQ

Organización XVII SIJ-RSEQ

Varios componentes del grupo se han encargado de organizar el XVII Simposio de Investigadores Jóvenes de la RSEQ, celebrado en Alcalá de Henares del 23 al 26 de noviembre.

XVII Simposio de Investigadores Jóvenes de la RSEQ

Además, ha contribuido con diversas contribuciones:

– Oral:
· Synthesis of seven- and eight-membered rings by Brønsted acid-catalyzed cyclization of biphenyl embedded trienynes
Jaime Tostado Sánchez, Juan J. Vaquero, Manuel A. Fernández-Rodríguez

– Flash:
· Enantio- and diastereoselective cyclopropanation of trans-alkenylboronates: Synthesis of versatile (trifluoromethyl)cyclopropylboronates
Julia Altarejos, David Sucunza, Juan José Vaquero, Javier Carreras

– Poster:
· Synthesis of a series of novel bicyclic amino acids
Álvaro González, Francisco José Torrero, José Luis Aceña, Juan José Vaquero

· Metal-free straightforward synthesis of boron-functionalized indenes and fulvenes by borylative cyclization
Ester Sans Panadés, Patricia García-García, Juan J. Vaquero, Cintia Virumbrales, Roberto Sanz, Manuel A. Fernández-Rodríguez

· SYNTHESIS OF PEPTIDE NUCLEIC ACIDS (PNAs) FOR THE TREATMENT OF CHRONIC KIDNEY DISEASE
Francisco Maqueda Zelaya, Verónica Miguel, José Luis Aceña, Santiago Lamas, Juan José Vaquero

· Synthesis of 4-membered rings fused lactams by gold(I) catalyzed
cyclization of alkynylcyclobutanamides
Guillermo G. Otárola, María Soledad Garre, Estíbaliz Merino, David Sucunza, Juan J. Vaquero, Patricia García-García

· Regioselective Ir-Catalyzed C−H Borylation of 4a,8a-Dihydro-4a-Aza-8a-Boranaphthalene
Isabel Valencia, Patricia García, David Sucunza, Juan J. Vaquero

· DEVELOPMENT OF A SYNTHETIC ROUTE TO LAETEVIRENOL A
Lucía Sánchez-Jiménez, Ana Milián, Jaime Tostado, Juan J. Vaquero, Patricia García-García, Manuel A. Fernández-Rodríguez

· Kinetic resolution in transannular Morita-Baylis-Hillman reaction:
approach to the synthesis of guaiane-type sesquiterpenes
Rubén Manzano, Raquel Mato, Efraím Reyes, Liher Prieto, Uxue Uria, Luisa Carrillo, Jose L. Vicario

· Electrochemical synthesis of aryl iodides from arylhydrazines
Clara Mañas Hernández, Guillermo Otárola, Estíbaliz Merino, Noemi Salardón, Belén Batanero

2021, AzaBN, Publicación

Valencia et al. J Org Chem. 2021;:. 1,10a-Dihydro-1-aza-10a-boraphenanthrene and 6a,7-Dihydro-7-aza-6a-boratetraphene: Two New Fluorescent BN-PAHs.

Publicaciones > Valencia et al

J Org Chem. 2021 Nov 22. doi: 10.1021/acs.joc.1c01095. PubMed 34806882

1,10a-Dihydro-1-aza-10a-boraphenanthrene and 6a,7-Dihydro-7-aza-6a-boratetraphene: Two New Fluorescent BN-PAHs.

Isabel Valencia1, Patricia García-García1, David Sucunza1, Francisco Mendicuti2, Juan J Vaquero1

1. Departamento de Química Orgánica y Química Inorgánica, Instituto de Investigación Química "Andrés M. del Río" (IQAR), Universidad de Alcalá, IRYCIS, Campus Científico-Tecnológico, 28805 Alcalá de Henares, Spain.  2. Departamento de Química Analítica, Química Física e Ingeniería Química, Instituto de Investigación Química "Andrés M. del Río" (IQAR), Universidad de Alcalá, Campus Científico-Tecnológico, 28805 Alcalá de Henares, Spain.

Abstract

Previously unknown 1,10a-dihydro-1-aza-10a-boraphenanthrene and 6a,7-dihydro-7-aza-6a-boratetraphene have been efficiently synthesized. Bromination of these BN-PAHs proceeds with complete regioselectivity, resulting in the formation of different substituted derivatives via cross-coupling reactions. These compounds exhibit rather high fluorescence quantum yields (up to ϕ(F) = 0.80).

Noticias

Nuevo artículo, J. Org. Chem. 11.21

1,10a-Dihydro-1-aza-10a-boraphenanthrene and 6a,7-Dihydro-7-aza-6a-boratetraphene: Two New Fluorescent BN-PAHs

Isabel Valencia, Patricia García-García, David Sucunza*, Francisco Mendicuti, Juan J. Vaquero*

J. Org. Chem. 2021, 86, 23, 16259–16267
DOI: 10.1021/acs.joc.1c01095

Previously unknown 1,10a-dihydro-1-aza-10a-boraphenanthrene and 6a,7-dihydro-7-aza-6a-boratetraphene have been efficiently synthesized. Bromination of these BN-PAHs proceeds with complete regioselectivity, resulting in the formation of different substituted derivatives via cross-coupling reactions. These compounds exhibit rather high fluorescence quantum yields (up to ϕF = 0.80).
Noticias

Nuevo artículo, Commun. Chem. 10.21

Two-photon activated precision molecular photosensitizer targeting mitochondria

Inês F. A. Mariz, Sandra N. Pinto, Ana M. Santiago, José M. G. Martinho, Javier Recio, Juan J. Vaquero, Ana M. Cuadro,* Ermelinda Maçôas*

Commun Chem 2021, 4, 142
DOI: 10.1038/s42004-021-00581-4

Mitochondria metabolism is an emergent target for the development of novel anticancer agents. It is amply recognized that strategies that allow for modulation of mitochondrial function in specific cell populations need to be developed for the therapeutic potential of mitochondria-targeting agents to become a reality in the clinic. In this work, we report dipolar and quadrupolar quinolizinium and benzimidazolium cations that show mitochondria targeting ability and localized light-induced mitochondria damage in live animal cells. Some of the dyes induce a very efficient disruption of mitochondrial potential and subsequent cell death under two-photon excitation in the Near-infrared (NIR) opening up possible applications of azonia/azolium aromatic heterocycles as precision photosensitizers. The dipolar compounds could be excited in the NIR due to a high two-photon brightness while exhibiting emission in the red part of the visible spectra (600–700 nm). Interaction with the mitochondria leads to an unexpected blue-shift of the emission of the far-red emitting compounds, which we assign to emission from the locally excited state. Interaction and possibly aggregation at the mitochondria prevents access to the intramolecular charge transfer state responsible for far-red emission.
2021, BioImag, Publicación

Mariz et al. Commun. Chem. 2021;4(1):142. Two-photon activated precision molecular photosensitizer targeting mitochondria.

Publicaciones > Mariz et al

Commun. Chem. 2021; 4(1):142. doi: 10.1038/s42004-021-00581-4

Two-photon activated precision molecular photosensitizer targeting mitochondria.

Inês F. A. Mariz, Sandra N. Pinto, Ana M. Santiago, José M. G. Martinho, Javier Recio, Juan J. Vaquero, Ana M. Cuadro, Ermelinda Maçôas

Resumen

Mitochondria metabolism is an emergent target for the development of novel anticancer agents. It is amply recognized that strategies that allow for modulation of mitochondrial function in specific cell populations need to be developed for the therapeutic potential of mitochondria-targeting agents to become a reality in the clinic. In this work, we report dipolar and quadrupolar quinolizinium and benzimidazolium cations that show mitochondria targeting ability and localized light-induced mitochondria damage in live animal cells. Some of the dyes induce a very efficient disruption of mitochondrial potential and subsequent cell death under two-photon excitation in the Near-infrared (NIR) opening up possible applications of azonia/azolium aromatic heterocycles as precision photosensitizers. The dipolar compounds could be excited in the NIR due to a high two-photon brightness while exhibiting emission in the red part of the visible spectra (600–700 nm). Interaction with the mitochondria leads to an unexpected blue-shift of the emission of the far-red emitting compounds, which we assign to emission from the locally excited state. Interaction and possibly aggregation at the mitochondria prevents access to the intramolecular charge transfer state responsible for far-red emission.