On March 2025, new students of the Master’s in Drug Discovery (UCM, UAH, CEU) have joined our group. During these months they will be carry out their Master’s Thesis Projects within the Biological Chemistry Group at the University of Alcalá  in the Department of Organic and Inorganic Chemistry:

• Dulce Contreras Morón
• Raquel Reyes Ballesteros
• Nuria Fernández Roca
• Javier Miñones Ginarte
• Jacqueline Valencia Esparza
• Isabel Fuentes López
• Samuel Guzmán Punzón

During the time with us, they will have access to state-of-the-art facilities and will work alongside experienced researchers and members of the group.

We wish you all a successful and rewarding experience and extend a warm welcome!

The University of Alcalá has awarded the Best Patent Award 2024 to two members of the Biological Chemistry Research Group, Dr. David Sucunza and Prof. Juan José Vaquero. The award recognizes their work and the research in the patent: Soluciones para diálisis peritoneal que contienen un flavonoide natural como agente osmótico (WO2024008987).

The patent, registered in collaboration with CSIC, claims for solutions for peritoneal dialysis containing a natural flavonoid as an osmotic agent. The present invention refers to peritoneal dialysis solutions that comprise troxerutin or vitamin P4 as an osmotic agent. The invention also refers to the procedure for preparing said solutions and to the novel use of troxerutin.

Congrats!!

Dr. Arkaiz Correa

Dra. Arkiz Correa, Permamanent Researcher at the Organic Chemistry Department of the Universidad del País Vasco (UPV/EHU), Spain
“Late-Stage C–H Functionalization of Amino Acids & Peptides”

Sala de Grados, Faculty of Pharmacy, UAH. Dec 03th, 12.15.

Identification and study of new NF-κB-inducing kinase ligands derived from the imidazolone scaffold

Francisco Maqueda-Zelaya, Lara Valiño-Rivas, Ana Milián, Sara Gutiérrez, José Luis Aceña, Javier Garcia-Marin,* Mª Dolores Sánchez-Niño, Juan J. Vaquero, Alberto Ortiz*

Arch. Pharm. ASAP
DOI: 10.1021/ardp.20240061

Chronic kidney disease (CKD) is a growing health concern, projected to be a major cause of death by 2040, due to an increasing risk of acute kidney injury (AKI). Systems biology-derived data suggest that the unmet need for an orally available drug to treat AKI and improve CKD outcomes may be addressed by targeting kidney inflammation and, specifically, nuclear factor κB-inducing kinase (NIK), a key signaling molecule that activates the noncanonical nuclear factor κB (NF-κB) pathway. We have prepared and identified a small family of imidazolone derivatives that bind NIK and inhibit the noncanonical NF-κB activation pathway. The introduction of heterocyclic substituents in position 2 of the imidazolone core provides compounds with affinity against human NIK. Three candidates, with best affinity profile, were tested in phenotypic experiments of noncanonical NF-κB activation, confirming that the derivative bearing the 4-pyridyl ring can inhibit the processing of NFκB p100 to NFkB2 p52, which is NIK-dependent in cultured kidney tubular cells. Finally, exhaustive docking calculations combined with molecular dynamics studies led us to propose a theoretical binding mode and rationalize affinity measures, in which the aminopyridine motif is a key anchoring point to the hinge region thanks to several hydrogen bonds and the interaction of heterocyclic rings in position 2 with Ser476 and Lys482. Our result will pave the way for the development of potential drug candidates targeting NIK in the context of CKD.

Alkanes C1–C6 C–H Bond Activation via a Barrierless Potential Energy Path: Trifluoromethyl Carbenes Enhance Primary C–H Bond Functionalization

Jonathan Martínez-Laguna, Julia Altarejos, M. Ángeles Fuentes, Giuseppe Sciortino, Feliu Maseras,* Javier Carreras,* Ana Caballero,* Pedro J. Pérez*

JACS 2024, ASAP
DOI: 10.1021/jacs.4c13065

XX Simposio de Jóvenes Investigadores Químicos de la RSEQ

Ciudad Real (Spain), 18 – 91 November

The Chemical Biology Group from the University of Alcalá was well represented in the Young Research Symposium of the Spanish Royal Society of Chemistry hold in the city of Ciudad Real.

– Flash + Poster:
· Modulating the pseudokinase integrin-linked kinase through new small molecules
Marta Durán, Mercedes Griera Merino, Ana María Carozo, Sergio de Frutos García, José Luis Aceña, Laura Calleros, Diego Rodríguez Puyol, Javier García-Marín

– Poster:
· 1,1-Diamine scaffold synthesis under visible light irradiation
Guillermo Morales-Ortega, Javier Carreras

– Poster:
· Acid-mediated synthesis of fluorescent functionalized polycycles via catiionic cyclization of o-acryloyl-o’alkynylbiaryls
Alex Hipólito-Barriuso, Patricia García-García, Manuel Á. Fernández-Rodgríguez

Our research group members, Álvaro González and Clara Mañas were  at the recent doctoral hooding ceremony at the University of Alcalá. Accompanied by their thesis advisors,Dr. Juan J. Vaquero and Dr. Estíbaliz Merino, they celebrated the achievements of the new Ph.D. recipients.

Congrats!!

Combined Gold and Photoredox Catalysis: Synthesis of 3-Alkenyl-2H-Indazoles from 2-Alkynylazobenzenes

Clara Mañas, Estíbaliz Merino*

We disclose the intramolecular synthesis of 3-alkenyl-2<i>H</i>-indazoles from 2-alkynylazobenzenes promoted by a dual catalysis using AuCl3 and a ruthenium photocatalyst under irradiation with visible light. This reaction goes through a hydroamination of the alkynyl fragment. The yields are governed by the electronic factors. Control experiments and DFT calculations suggest that a radical and polar mechanisms are operating in parallel. This transformation goes through first formation and C-N bond and 1,2-hydride shift. Derivatization was also carried out to extend the versatility of this methodology.

Adv. Synth. Cat. 2024
DOI: 10.1002/adsc.202400990

Copper-Catalyzed Hydroamination of 2-Alkynylazobenzenes: Synthesis of 3-Alkenyl-2H-Indazole

Clara Mañas, Juan Herrero-Bourdieu, Estíbaliz Merino*

A copper-catalyzed intramolecular synthesis of 3-alkenyl-2H-indazoles from 2-alkynylazobenzenes is described. The reaction proceeds in a single step via C–N bond formation and a subsequent 1,2-hydride shift, affording products in high yields. DFT calculations suggest the 1,2-hydride shift as the rate-determining step. Further derivatization enables functionalization of the 3-alkenyl-2H-indazoles.

J. Org. Chem. 2024.
DOI: 10.1021/acs.joc.4c02144