Category Archives: Publicación

2020, BioImag, Publicación

Garre et al. J Org Chem. 2020;85(2):441-448. Synthesis and Photophysical Behavior of a Highly Fluorescent Family of Unsymmetrical Organoboron Complexes Containing 5-(Pyridin-2-ylmethylene)imidazolidine-2,4-dione Moieties.

Publications > Garre et al

J Org Chem. 2020, 85, 441 PubMed 31858801

Synthesis and Photophysical Behavior of a Highly Fluorescent Family of Unsymmetrical Organoboron Complexes Containing 5-(Pyridin-2-ylmethylene)imidazolidine-2,4-dione Moieties.

M Soledad Garre1, Raul Losantos2, Sara Gutierrez1, David Sucunza1, Patricia Garcia-Garcia1, Diego Sampedro2, Juan J Vaquero1

1. Departamento de Quimica Organica y Quimica Inorganica, Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR) , Universidad de Alcala, IRYCIS , 28805 Alcala de Henares , Spain.  2. Departamento de Quimica, Centro de Investigacion en Sintesis Quimica (CISQ) , Universidad de La Rioja , Madre de Dios 53 , 26006 Logrono , Spain.

Abstract

A new and highly fluorescent family of unsymmetrical organoboron complexes containing 5-(pyridin-2-ylmethylene)imidazolidine-2,4-dione moieties has been synthesized in three steps. These compounds show strong absorptions covering a wide range of the UV-vis spectrum and are strongly emissive (varphif of up to 0.92 in CH3CN). Moreover, two fluorophores that include an alkyne or an azide group at the end of the alkyl chain and with potential utility in bioorthogonal chemistry have been developed. One of these, in which the glycol substituent provides an enhanced water solubility without compromising the fluorescence (varphif = 0.85 in water), may be of particular importance.

2019, AzaBN, Publicación

Abengozar et al. J Org Chem. 2019;84(11):7113-7122. A New Member of the BN-Phenanthrene Family: Understanding the Role of the B-N Bond Position.

Publications > Abengozar et al

J Org Chem. 2019, 84, 7113

A New Member of the BN-Phenanthrene Family: Understanding the Role of the B-N Bond Position.

Alberto Abengozar1, David Sucunza1, Patricia Garcia-Garcia1, Diego Sampedro2, Adrian Perez-Redondo1, Juan J Vaquero1

1. Departamento de Quimica Organica y Quimica Inorganica, Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR) , Universidad de Alcala , 28805 Alcala de Henares , Spain.  2. Departamento de Quimica, Centro de Investigacion en Sintesis Quimica (CISQ) , Universidad de La Rioja , Madre de Dios 53 , 26006 Logrono , Spain.

Abstract

3,4-Dihydro-4-aza-3-boraphenanthrene, which shows the highest fluorescence quantum yield of all nonsubstituted BN-phenanthrenes reported to date (varphiF = 0.61), has been synthesized in only three steps (76% overall yield) from easily accessible 1-bromo-2-vinylnaphthalene, along with several substituted derivatives. The reactivity of these previously unknown BN-aromatic compounds toward organolithium compounds and bromine has been studied. This latter reaction affords bromo-substituted compounds that are suitable for further functionalization via Suzuki and Sonogashira couplings, with complete regioselectivity. The optical properties and excited state deactivation mechanisms of selected compounds were studied using computational methods.

2019, AzaBN, Publicación

Abengozar et al. Beilstein J Org Chem. 2019;15:1257-1261. Remarkable effect of alkynyl substituents on the fluorescence properties of a BN-phenanthrene.

Publications > Abengozar et al

Beilstein J. Org. Chem. 2019, 15, 1257 PubMed 31293672

Remarkable effect of alkynyl substituents on the fluorescence properties of a BN-phenanthrene.

Alberto Abengozar, David Sucunza, Patricia Garcia-Garcia, Juan J Vaquero

Departamento de Quimica Organica y Quimica Inorganica, Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR), Universidad de Alcala, 28871-Alcala de Henares, Madrid, Spain.

Keywords: BN-phenanthrene; alkyne; cross-coupling; fluorescence; heterocycles

Abstract

A series of BN-phenanthrenes with substituents of a diverse nature have been synthesized by palladium-catalyzed cross-coupling reactions of a common chloro-substituted precursor, which was made from readily available materials in only four steps. Evaluation of the photophysical properties of the prepared compounds unveiled an impressive effect of the presence of alkynyl substituents on the fluorescence quantum yield, which improved from 0.01 in the parent compound to up to 0.65 in derivatives containing a triple bond.

2019, Publicación, Renal

Valino-Rivas et al. Trends Mol Med. 2019;25(4):341-360. NIK as a Druggable Mediator of Tissue Injury.

Publications > Valino-Rivas et al

Trends Mol Med. 2019, 25, 341 PubMed 30926358

NIK as a Druggable Mediator of Tissue Injury.

Lara Valino-Rivas1, Juan Jose Vaquero2, David Sucunza2, Sara Gutierrez2, Ana B Sanz1, Manuel Fresno3, Alberto Ortiz1, 4, a, Maria Dolores Sanchez-Nino1, 4, a

1. Department of Nephrology and Hypertension, Instituto de Investigacion Sanitaria (IIS) Fundacion Jimenez Diaz, School of Medicine, Universidad Autonoma de Madrid (UAM), Red de Investigacion Renal (REDINREN), and Fundacion Renal Inigo Alvarez de Toledo (FRIAT), Madrid, Spain.  2. Departamento de Quimica Organica y Quimica Inorganica, Universidad de Alcala and REDINREN, Madrid, Spain.  3. Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas de la UAM, Madrid, Spain.  4. These authors contributed equally. Electronic address:.

a. aortiz@fjd.es  a. mdsanchez@fjd.es

Keywords: *MAP3K14; *NIK; *TWEAK; *acute kidney injury; *apoptosis; *autoimmunity; *cell death; *chronic kidney disease; *cirrhosis; *diabetes; *epigenetic; *esteatohepatitis; *hepatitis; *inflammation; *mantle lymphoma; *myeloid leukemia; *osteoporosis; *sarcopenia; *verteporfin

Abstract

NF-kappaB-inducing kinase (NIK, MAP3K14) is best known as the apical kinase that triggers non-canonical NF-kappaB activation and by its role in the immune system. Recent data indicate a role for NIK expressed by non-lymphoid cells in cancer, kidney disease, liver injury, glucose homeostasis, osteosarcopenia, vascular calcification, hematopoiesis, and endothelial function. The spectrum of NIK-associated disease now ranges from immunodeficiency (when NIK is defective) to autoimmunity, cancer, sterile inflammation, fibrosis, and metabolic disease when NIK is overactive. The development of novel small-molecule NIK inhibitors has paved the way to test NIK targeting to treat disease in vivo, and may eventually lead to NIK targeting in the clinic. In addition, NIK activators are being explored for specific conditions such as myeloid leukemia.

2019, AzaBN, Publicación

Abengozar et al. Org Lett. 2019;21(8):2550-2554. Synthesis, Functionalization, and Optical Properties of 1,2-Dihydro-1-aza-2-boraphenanthrene and Several Highly Fluorescent Derivatives.

Publications > Abengozar et al

Org Lett. 2019, 21, 2550 PubMed 30951317

Synthesis, Functionalization, and Optical Properties of 1,2-Dihydro-1-aza-2-boraphenanthrene and Several Highly Fluorescent Derivatives.

Alberto Abengozar1, Patricia Garcia-Garcia1, David Sucunza1, Diego Sampedro2, Adrian Perez-Redondo1, Juan J Vaquero1

1. Departamento de Quimica Organica y Quimica Inorganica, Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR) , Universidad de Alcala , 28805 Alcala de Henares , Spain.  2. Departamento de Quimica, Centro de Investigacion en Sintesis Quimica (CISQ) , Universidad de La Rioja , Madre de Dios 53 , 26006 Logrono , Spain.

Abstract

Previously unknown 1,2-dihydro-1-aza-2-boraphenanthrene has been synthesized in only three steps from 2-bromo-1-vinylnaphthalene. The reactivity of this new BN-phenanthrene, and of several substituted derivatives, has been tested against bromine and organolithium compounds. Bromination proceeded with complete regioselectivity, affording bromo-substituted compounds suitable for further functionalization via cross-coupling reactions. This new family of BN-phenanthrenes exhibits a substantial increase in the quantum yield (up to varphiF = 0.93) with respect to phenanthrene.

2019, Au, Publicación

Garre et al. J Org Chem. 2019;:. Regiodivergent Electrophilic Cyclizations of Alkynylcyclobutanes for the Synthesis of Cyclobutane-Fused O-Heterocycles.

Publications > Garre et al

J. Org. Chem. 2019, 84, 9, 5712 PubMed 30896164

Regiodivergent Electrophilic Cyclizations of Alkynylcyclobutanes for the Synthesis of Cyclobutane-Fused O-Heterocycles.

M Soledad Garre1, David Sucunza1, Enrique Aguilar2, Patricia Garcia-Garcia1, Juan J Vaquero1

1. Departamento de Quimica Organica y Quimica Inorganica, Campus Cientifico-Tecnologico, Facultad de Farmacia , Universidad de Alcala (IRYCIS) , Autovia A-II, Km 33.1 , 28805 Alcala de Henares , Madrid , Spain.  2. Departamento de Quimica Organica e Inorganica, Instituto Universitario de Quimica Organometalica "Enrique Moles" , Universidad de Oviedo , C/Julian Claveria, 8 , 33006 Oviedo , Spain.

Abstract

Cyclobutane-fused dihydropyrans and methylenetetrahydrofurans are highly interesting cores found in numerous natural products. Both these cores are selectively prepared from a common alkynylcyclobutane precursor bearing an appended hydroxyl group herein. Thus, cyclobutane-fused dihydropyrans can be obtained by a selective 6-endo-dig iodocyclization, whereas gold-catalyzed 5-exo-dig cycloisomerization provides a bicyclic core containing a methylenetetrahydrofuran moiety as major product. Several cyclobutane-fused O-heterocycles with diverse substituents are synthesized following the reported methodology.

2019, Publicación, Renal

Cuarental et al. Nefrología 2019

Publications > article

Nefrologia 2019, 39, 568 PubMed 31196660

MAP3K kinases and kidney injury.

Leticia Cuarental, David Sucunza, Lara Valino-Rivas, Beatriz Fernandez-Fernandez, Ana Belen Sanz, Alberto Ortiz, Juan Jose Vaquero, Maria Dolores Sanchez-Nino

Palabras clave: *ASK1; *Acute kidney injury; *Diabetic kidney disease; *Enfermedad renal cronica; *Enfermedad renal diabetica; *Kidney; *MAP3K kinases; *MAP3K quinasas; *MAP3K14; *NF-kappaB; *NIK; *Rinon; *Selonsertib; *TWEAK

Resumen

Mitogen-activated protein kinases (MAP kinases) are functionally connected kinases that regulate key cellular process involved in kidney disease such as all survival, death, differentiation and proliferation. The typical MAP kinase module is composed by a cascade of three kinases: a MAP kinase kinase kinase (MAP3K) that phosphorylates and activates a MAP kinase kinase (MAP2K) which phosphorylates a MAP kinase (MAPK). While the role of MAPKs such as ERK, p38 and JNK has been well characterized in experimental kidney injury, much less is known about the apical kinases in the cascade, the MAP3Ks. There are 24 characterized MAP3K (MAP3K1 to MAP3K21 plus RAF1, BRAF and ARAF). We now review current knowledge on the involvement of MAP3K in non-malignant kidney disease and the therapeutic tools available. There is in vivo interventional evidence clearly supporting a role for MAP3K5 (ASK1) and MAP3K14 (NIK) in the pathogenesis of experimental kidney disease. Indeed, the ASK1 inhibitor Selonsertib has undergone clinical trials for diabetic kidney disease. Additionally, although MAP3K7 (MEKK7, TAK1) is required for kidney development, acutely targeting MAP3K7 protected from acute and chronic kidney injury; and targeting MAP3K8 (TPL2/Cot) protected from acute kidney injury. By contrast MAP3K15 (ASK3) may protect from hypertension and BRAF inhibitors in clinical use may induced acute kidney injury and nephrotic syndrome. Given their role as upstream regulators of intracellular signaling, MAP3K are potential therapeutic targets in kidney injury, as demonstrated for some of them. However, the role of most MAP3K in kidney disease remains unexplored.

2018, Publicación, Renal

Gutierrez et al. Eur J Med Chem. 2018;157:946-959. Discovery of potent calpain inhibitors based on the azolo-imidazolidenone.

Publications > Gutierrez et al

Eur J Med Chem. 2018, 157, 946 PubMed 30165342

Discovery of potent calpain inhibitors based on the azolo-imidazolidenone.

Sara Gutierrez1, Maria Moron1, Mercedes Griera2, David Sucunza1, Laura Calleros2, Andrea Garcia-Jerez2, Claire Coderch3, Francisco J Hermoso3, Carolina Burgos1, Manuel Rodriguez-Puyol2, Beatriz de Pascual-Teresa3, Maria L Diez-Marques2, Antonio Jimenez2, Miguel Toro-Londono2, Diego Rodriguez-Puyol4, Juan J Vaquero1

1. Departamento de Quimica Organica y Quimica Inorganica, Universidad de Alcala.  2. Departamento de Biologia de Sistemas, Universidad de Alcala, 28871, Alcala de.  3. Departamento de Quimica y Bioquimica, Facultad de Farmacia, Universidad San.  4. Research Unit and Nephrology Section, Hospital Principe de Asturias and.

Keywords: Azolo-imidazolidenone; Blockade of apoptosis; Calpain inhibitors; SAR; Uncompetitive inhibition

Abstract

A series of new azolopyrimidine-peptide hybrids and indolomethylideneimidazolones

2018, AzaBN, Publicación

Abengozar et al. Org Lett. 2018;20(16):4902-4906. C-H Functionalization of BN-Aromatics Promoted by Addition of Organolithium Compounds to the Boron Atom.

Publications > Abengozar et al

Org Lett. 2018, 20, 4902 PubMed 30070487

C-H Functionalization of BN-Aromatics Promoted by Addition of Organolithium Compounds to the Boron Atom.

Alberto Abengozar1, Miguel Angel Fernandez-Gonzalez2, David Sucunza1, Luis Manuel Frutos2, Antonio Salgado3, Patricia Garcia-Garcia1, Juan J Vaquero1

1. Departamento de Quimica Organica y Quimica Inorganica, Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR) , Universidad de Alcala , 28805 Alcala de Henares , Madrid , Spain.  2. Departamento de Quimica Analitica, Quimica Fisica e Ingenieria Quimica, Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR) , Universidad de Alcala , 28805 Alcala de Henares , Madrid , Spain.  3. Centro de Espectroscopia de Resonancia Magnetica Nuclear (CERMN), CAI Quimicas , Universidad de Alcala , 28805 Alcala de Henares , Madrid , Spain.

Abstract

Addition of an organolithium compound to a BN-phenanthrene with embedded B and N atoms is proposed to result in coordination of RLi to the boron atom. This coordination, supported by NMR spectroscopy and DFT calculations, increases the nucleophilicity of the system in the beta position to the N atom and is therefore a useful tool for promoting regioselective C-H functionalization of BN aromatics.

2018, Publicación, TosMIC

Gutierrez et al. J Org Chem. 2018;83(12):6623-6632. gamma-Carboline Synthesis by Heterocyclization of TosMIC Derivatives.

Publications > Gutierrez et al

J Org Chem. 2018, 83, 6623 PubMed 29756452

gamma-Carboline Synthesis by Heterocyclization of TosMIC Derivatives.

Sara Gutierrez, David Sucunza, Juan J Vaquero

Departamento de Quimica Organica y Quimica Inorganica and Instituto de Investigacion Quimica "Andres M. del Rio" (IQAR) , Universidad de Alcala , 28805 - Alcala de Henares , Madrid , Spain.

Abstract

A new method for the synthesis of gamma-carbolines by a heterocyclization that involves alpha-indol-2-ylmethyl TosMIC derivatives and different electrophiles has been developed. This methodology has been successfully applied to the synthesis of several highly substituted gamma-carbolines.