Artículos (Química Orgánica)
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Artículo Azobenzene-bridged ionizable amphiphilic Janus glycosides for lightcontrolled, single-component and organmodulable pDNA delivery(Nature Research, 2026-02-05) Wang, Zhaoxin; Rivero Barbarroja, Gonzalo; Benito, Juan M.; Maisonneuve, Stéphane; Vélaz, Itziar; Juárez Gonzálvez, Inmaculada; Garrido, María J.; Tros de Ilarduya, Conchita; Ortiz Mellet, Carmen; Xie, Juan; García Fernández, José M.; Química Orgánica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. EspañaStimuli-responsive supramolecular systems enable spatiotemporal control of nucleic acid (NA) delivery. To achieve precise and programmable vectors, we designed azobenzene-bridged ionizable amphiphilic Janus glycosides (IAJGs) as single-component, light-responsive DNA carriers. These glucopyranose-based dimers undergo reversible E/Z photoisomerization while forming stable nanocomplexes with plasmid DNA (pDNA). Photoisomerization alters nanocomplex size, surface charge, and internal order, resulting in distinct transfection outcomes. In vitro, O- and S-glycoside derivatives displayed isomer-dependent activity across COS-7, HepG2, and RAW264.7 cells, with pronounced switching effects specially in macrophages. In vivo, systemic administration revealed organ-selective responses:O-glycosides shifted expression from liver to lung upon E→Z conversion, whereas S-glycosides favored spleen targeting. All formulations maintained high cell viability. These results highlight photoswitchable IAJGs as structurally defined vectors for adjustable control over NA delivery and organ tropism.Artículo Asymmetric hydrogenation of 3H-azepines via catalytic kinetic resolution: access to anti-disubstituted azepanes(RSC, 2026-03) Bui, L.; Berna Yildiz, Dilara; García Matesanz, Diego; Matador Martínez, Esteban; Sánchez, Raquel; Atodiresei, Iuliana; Lonardi, Giovanni; Leonori, Daniele; Química OrgánicaAzepanes are increasingly valued scaffolds in drug discovery, yet general asymmetric methods for their synthesis remain elusive. This limitation is particularly evident for polysubstituted derivatives bearing stereocenters remote from the nitrogen atom, for which asymmetric access is essentially absent. Here we report the first asymmetric hydrogenation of 3H-azepines, enabling direct access to anti-configured azepanes with excellent diastereo- and enantioselectivity (>20 : 1 dr, up to 99 : 1 er). The transformation is mediated by an iridium catalyst featuring a mixed-ligand system composed of a chiral phosphoramidite and an achiral phosphine. Mechanistic studies reveal an unusual sequential pathway in which an initial reduction generates an N-protected intermediate with low enantioselectivity, that subsequently undergoes a highly selective catalytic kinetic resolution. This work provides a catalytic solution to the asymmetric synthesis of disubstituted azepanes and expands the scope of asymmetric hydrogenation to anti-selective outcomes beyond classical enantiofacial discrimination.Artículo Cytotoxicity Evaluation of Chalcones and Flavanones from the Leaves of Corema album (L.) D. Don(MDPI, 2026-03-28) Canoyra, Antonio; Acero, Nuria; Muñoz-Mingarro, Dolores; León González, Antonio José; Espartero Sánchez, José Luis; Martín Cordero, Carmen; Farmacología; Química Orgánica; Agencia Estatal de Investigación. España; Ministerio de Ciencia, Innovación y Universidades (MICIU). Españafirst_pageDownload PDFsettingsOrder Article Reprints Open AccessArticle Cytotoxicity Evaluation of Chalcones and Flavanones from the Leaves of Corema album (L.) D. Don by Antonio Canoyra 1ORCID,Nuria Acero 1ORCID,Dolores Muñoz-Mingarro 2ORCID,Antonio J. León-González 3ORCID,José Luis Espartero 4ORCID andCarmen Martín-Cordero 3,*ORCID 1 Pharmaceutical and Health Science Department, Pharmacy Faculty, San Pablo-CEU University, CEU Universities, Urbanización Montepríncipe, Boadilla del Monte, 28660 Madrid, Spain 2 Chemistry and Biochemistry Department, Pharmacy Faculty, San Pablo-CEU University, CEU Universities, Urbanización Montepríncipe, Boadilla del Monte, 28660 Madrid, Spain 3 Department of Pharmacology, Faculty of Pharmacy, University of Seville, C/P. García González, 2, 41012 Seville, Spain 4 Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Seville, 41012 Sevilla, Spain * Author to whom correspondence should be addressed. Biomolecules 2026, 16(4), 509; https://doi.org/10.3390/biom16040509 Submission received: 22 February 2026 / Revised: 15 March 2026 / Accepted: 25 March 2026 / Published: 28 March 2026 (This article belongs to the Special Issue Phytochemicals: Bioactivity in Disease Prevention, Anti-Inflammation, and Animal/Human Health) Downloadkeyboard_arrow_down Browse Figures Review Reports Versions Notes Abstract In a preliminary screening of phytochemical compounds from Andalusian vascular plants, the ethyl acetate extract obtained from the leaves of Corema album (L.) D. Don (Ericaceae) was selected due to its cytotoxic activity. Eight phenolic compounds were isolated from this extract: four chalcones (2′,4′-dihydroxydihydrochalcone, 2′,4′-dihydroxychalcone, 2′,4′-dihydroxy-6′-methoxydihydrochalcone, 2′-methoxy-4′-hydroxydihydrochalcone) and four flavanones (pinocembrin, 6-methylpinocembrin, 6,8-dimethylpinocembrin and 7-O-prenylpinocembrin). Their structures were elucidated using 1H NMR and 13C NMR data, including 2D NMR, as well as mass spectrometry. These compounds were evaluated using the MTT cytotoxicity assay against human colorectal adenocarcinoma (HT-29) and renal adenocarcinoma (ACHN) cell lines. The chalcone 2′,4′-dihydroxychalcone exhibited greater cytotoxicity than the corresponding 2′,4′-dihydroxydihydrochalcone in both cell lines. The IC50 values (µM ± SEM) were 13.31 ± 0.48 and 9.43 ± 0.34 for the chalcone, and 62.23 ± 1.06 and 54.68 ± 1.62 for the dihydrochalcone, respectively. The introduction of methyl groups at positions 6 and 8 of pinocembrin increased cytotoxicity in the ACHN cell line. The IC50 values (µM ± SEM) were 91.28 ± 3.03 for pinocembrin, 64.36 ± 0.53 for 6-methylpinocembrin, and 28.74 ± 0.35 for 6,8-dimethylpinocembrin. These results highlight the leaves of C. album as a promising source of chalcones and flavanones with pharmacological interest.Artículo Strong Antiproliferative Activity Observed in Hammett-Guided Electronic Modulation of GPx-Mimetic Pathways in Aryl Selenoureas(MDPI, 2026) Begines Aguilar, Paloma; Pérez-Lage, Clara I.; Puerta, Adrián; Padrón, José M.; López López, Óscar; Fernández-Bolaños Guzmán, José María; Química Orgánica y Farmacéutica; Química Orgánica; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de AndalucíaOrganoselenium chemistry has undergone remarkable development over the past five decades, evolving from its initial association with high toxicity into a field with pivotal contributions to materials science, organic synthesis, catalysis, and Medicinal Chemistry. Among the diverse biological activities displayed by organoselenium compounds, their redox behaviour is particularly compelling, as many of these molecules act as efficient mimetics of the antioxidant enzyme glutathione peroxidase (GPx). In this work, we investigated the GPx-like activity of a series of N,N′-diaryl selenoureas toward the depletion of H2O2 and cumene hydroperoxide (CumOOH) as model ROS. Their reactivity was correlated with the electronic nature of the aryl substituents using a Hammett-type analysis, revealing a strong dependence of the reaction rate on remote electronic perturbations within the aromatic ring. Combined UV and NMR studies provided mechanistic evidence supporting a catalytic cycle in which selenoureas, operating at sub-stoichiometric loadings (1 mol%) and using a thiol as a cofactor-like molecule, can be used to efficiently scavenge ROS with half-lives of only a few minutes (~10–60 min). Furthermore, these selenoureas exhibited potent antiproliferative activity across several human solid tumour cell lines. Overall, these results offer mechanistic insight into the ROS-eliminating pathways of selenoureas and highlight their potential as chemopreventive or anticancer agents.Artículo Bioreduction of β-ketosulfides Using Deep Eutectic Solvents as Cosolvents(Wiley, 2026) Falcini, Chiara; Carvajal-Bárcena, Juan; Urban, Lucía V.; Colomer, Juan Pablo; Bisogno, Fabricio R.; Fernández Fernández, Rosario Fátima; Gonzalo Calvo, Gonzalo de; Química OrgánicaThe β-hydroxysulfide motif is present in both natural and synthetic compounds with notable bioactivities. Herein, the synthesis of aset of optically active (R)- and (S)-β-hydroxysulfides starting from β-ketosulfides using ketoreductases (KREDs) in nonconventionalmedia aqueous buffer/deep eutectic solvents (DESs) has been developed. Several Type III DESs have been tested as cosolvents,being observed for most of the biotransformations higher conversions and enantiomeric excesses in the presence of some glycerol-or ethylenglycol-based DESs. Bioreductions can be performed up to 70% v/v of DESs with good conversions, demonstratingthe high performance of these nonconventional media in biocatalyzed reductive processes. Additionally, it was observed thatthe lipase CalB partially retained activity in DES-containing media for the hydrolysis of β-alkylsulfide enol esters, thus beingpossible to develop a one-pot, two-enzyme cascade that combined CaalB-catalyzed hydrolysis of a β-alkylsulfide enol ester withthe subsequent KRED reduction of the β-ketosulfide obtained to the (R)-β-hydroxysulfide in both sequential and concurrent ways,affording high stereoselectivity.
Artículo Bicyclic picomolar OGA inhibitors enable chemoproteomic mapping of its endogenous post-translational modifications(American Chemical Society, 2022-01-05) González Cuesta, Manuel; Sidhu, Peter; Ashmus, Roger A.; Males, Alexandra; Proceviat, Cameron; Madden, Zarina; Rogalski, Jason C.; Busmann, Jill A.; Foster, Leonard J.; García Fernández, José M.; Davies, Gideon J.; Ortiz Mellet, Carmen; Vocadlo, David J.; Química Orgánica; Ministerio de Ciencia e Innovación (MICIN). España; British Columbia Knowledge Development; Canadian Institutes of Health Research (CIHR)Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. Despite the presence of O-GlcNAc on hundreds of proteins within cells, only two enzymes regulate this modification. One of these enzymes is O-GlcNAcase (OGA), a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated. Chemical tools to control OGA are emerging as essential resources for helping to decode the biochemical and cellular functions of the O-GlcNAc pathway. Here we describe rationally designed bicyclic thiazolidine inhibitors that exhibit superb selectivity and picomolar inhibition of human OGA. Structures of these inhibitors in complex with human OGA reveal the basis for their exceptional potency and show that they extend out of the enzyme active site cleft. Leveraging this structure, we create a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications. These data uncover a range of new modifications, including some that are less-known, such as O-ubiquitination and N-formylation. We expect that these inhibitors and chemoproteomics probes will prove useful as fundamental tools to decipher the mechanisms by which OGA is regulated and directed to its diverse cellular substrates. Moreover, the inhibitors and structures described here lay out a blueprint that will enable the creation of chemical probes and tools to interrogate OGA and other carbohydrate active enzymes.Artículo Structure of the O-antigen of the lipopolysaccharide isolated from Pantoea ananatis AEP17, a rhizobacterium associated with rice(Elsevier, 2013-03-22) Contreras Sánchez-Matamoros, Rocío; Gil Serrano, Antonio Miguel; Tejero Mateo, María Pilar; Ollero Márquez, Francisco Javier; Megías Saavedra, Esaú; Rodríguez Carvajal, Miguel Ángel; Química Orgánica; Microbiología; Ministerio de Educación y Ciencia (MEC). EspañaThe lipopolysaccharide of a Gram-negative bacterium having a putative plant-growth promoting activity (Pantoea ananatis AEP17) has been isolated and subjected to partial hydrolysis. The O-antigen has been studied by mass spectrometry and NMR experiments. On the basis of these experiments it is concluded that the following repeating unit is present in the polysaccharide: →3)-β-d-GlcpNAc-(1→3)[α-d-GalpAN-(1→2)]-α-l-Rhap-(1→2)-α-l-Rhap-(1→3)-α-l-Rhap-(1→2)-α-l-Rhap-(1→ The occurrence of d-galacturonamide (GalAN) is unusual in bacterial O-polysaccharides. It has only been reported in Escherichia coli O65 [Perry, M. B.; MacLean, L. L. Carbohydr. Res. 1999, 322, 57–66].
Artículo α-GalCer sp2-Iminoglycolipid Analogs as CD1d-dependent iNKT Modulators: Evaluation of Their Immunotherapeutic Potential in Murine Models of Asthma and Autoimmune Hepatitis(Elsevier, 2024-11-15) Lai, Alan Chuan Ying; González Cuesta, Manuel; Ho, Chieh Hsin; Chi, Po Yu; Wu, Ko Chien; Rocha, Gabriel; Muñoz García, Juan Carlos; Angulo Álvarez, Jesús; García Fernández, José M.; Chang, Ya Jen; Ortiz Mellet, Carmen; Química Orgánica; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; Junta de AndalucíaInvariant natural killer T (iNKT) cells are a subset of innate T cells displaying powerful immunomodulatory functions. Despite extensive preclinical research on the use of iNKT agonist and antagonist for various diseases, translating these findings into successful clinical applications has proven challenging, leaving no approved treatments to date. Efforts to optimize therapeutic outcomes by developing alternative glycolipids to α-galactosylceramide (α-GalCer or KRN7000), the prototypical iNKT antigen, have shown improved preclinical results. However, significant obstacles remain, including the relatively laborious synthesis of α-glycosides and their vulnerability to degradation by α-glycosidases. To overcome these limitations, we explored the use of sp2-iminosugars, a class of glycomimetics, to replace the carbohydrate moiety in α-GalCer-like glycolipids. This substitution offers enhanced biostability and precise control over α-selectivity in glycosylation reactions. The resulting sp2-iminoglycolipids (sp2-IGLs) were tested for their immunomodulatory effects, demonstrating the ability to bind the α-GalCer binding site on the CD1d protein in antigen-presenting cells (APCs), and functioning as iNKT antagonists in α-GalCer-stimulated splenocytes. Notably, analogs featuring a 4-alkyl-1,2,3-aminotriazol-1-yl segment in place of the C25 N-acyl tail in α-GalCer additionally exhibited mild agonistic activity in the absence of α-GalCer stimulation. Computational studies support the formation of stable CD1d– sp2-IGL and CD1d – sp2-IGL – T-cell receptor complexes, with significant differences in the dynamics depending on the glycone nature and lipid tail length. These findings provide a molecular rationale for the observed experimental data. Furthermore, in vivo studies using murine models of asthma and autoimmune hepatitis have identified promising sp2-IGL candidates for further development in immunotherapy.Artículo Sulfoxidation reactions catalysed by the Baeyer-Villiger monooxygenase OTEMO from Pseudomonas putida ATCC 17453(Taylor and Francis, 2022-08) Gonzalo Calvo, Gonzalo de; Loncar, Nikola; Fraaije, Marco W.; Química OrgánicaThe Baeyer-Villiger monooxygenase OTEMO from Pseudomonas putida ATCC 17453 has been employed as biocatalyst in the asymmetric synthesis of a set of optically active sulfoxides. Several alkyl aryl sulfides are oxidised by this biocatalyst leading to the (S)-sulfoxides. Especially for those substrates containing electron-donating groups in the aromatic ring or in the alkyl moiety, good to high enantiopurities can be obtained. OTEMO is also able to perform the kinetic resolution of racemic sulfoxides, but with low enantioselectivities. Finally, parameters that can affect its biocatalytic properties, such as pH, temperature, organic cosolvents and substrate concentration, have been tested to get a better insight into the biocatalytic potential of this hitherto poorly explored oxidative biocatalyst.Artículo Structure of surface polysaccharides from Aeromonas sp AMG272, a plant-growth promoting rhizobacterium isolated from rice rhizosphere(Elsevier, 2018-06-15) Contreras Sánchez-Matamoros, Rocío; Gil Serrano, Antonio Miguel; Espuny Gómez, María del Rosario; Ollero Márquez, Francisco Javier; Megías, Manuel; Rodríguez Carvajal, Miguel Ángel; Microbiología; Química OrgánicaAeromonas sp. AMG272 is a Gram-negative bacterium that has been isolated from agricultural soil and studied for its plant growth-promoting activities. Structures of the O-specific polysaccharide chain of the AMG272 lipopolysaccharide and its capsular polysaccharide were elucidated using GLC-MS and NMR spectroscopy. The structure of the O-specific polysaccharide, →4)-α-L-Rhap-(1→3)-β-D-GlcpNAc-(1→, has been found in other Aeromonas strains and related bacteria, whereas the structure of the capsular polysaccharide has not been reported before: →6)[β-D-Fucp3NAc4Ac-(1→3)]-α-D-GlcpNAc-(1→4)-α-D-Galp-(1→3)-α-D-GalpNAc-(1→4)-α-D-Galp-(1→.Artículo Plant growth promoting vesicles: Molecular inoculants to enhance rhizobium-legume symbiosis(elsevier, 2026) Moreno De Castro, Natalia; Silva-Nunes, Rafaela Leopoldina; Ayala García, Paula; Herrero Gómez, Irene; Rodríguez Carvajal, Miguel Ángel; López Baena, Francisco Javier; Vinardell González, José María; Jiménez Guerrero, Irene; Borrero de Acuña, José Manuel; Pérez Montaño, Francisco de Asís; Microbiología; Química Orgánica; Junta de Andalucía; Ministerio de Ciencia e Innovación (MICIN). España; Agencia Estatal de Investigación. España; Conselho Nacional de Desenvolvimento Científico e Tecnologico. Brasil; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Brasil; Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul. BrasilBackground and purpose: Bacterial extracellular vesicles (commonly referred to as EVs) are proteolipidic structures detached from bacterial membranes into the surrounding environment. They participate in diverse biological processes, including interdomain communication as EV encapsulation concentrates signaling molecules for efficient delivery to target eukaryotic cells. While the rhizobium-legume symbiosis represents one of nature's most intimate partnerships, the role of rhizobial EVs, particularly as carriers of symbiotic signaling molecules, remains poorly understood. The primary aim of this study was to identify Nod Factors (NFs) within rhizobial EVs, exploring their potential as molecular inoculants to enhance the rhizobium-legume symbiosis. Methods: Sinorhizobium fredii HH103 EVs were characterized to confirm their integrity and yield. Their NF content was determined and quantified, comparing genistein-induced and non-induced cultures to identify specific chemical signatures. The biological impact of these EVs was validated through nodule primordia visualization and controlled growth chamber assays in Glycine max and Lotus japonicus. A two-year field experiment was conducted in South Brazil with 10 different treatments to explore the soybean (G. max Brasmax Zeus Ipro) responses to inoculation with plant-growth promoting bacteria (Azospirillum brasilense AbV5 and AbV6; Bradyrhizobium japonicum CCT 4065, SEMIA 5079, SEMIA 5080 and SEMIA 586) with or without HH103 EVs. Results: Our investigation explores the role of bacterial EVs produced by S. fredii HH103 in enhancing the symbiotic interaction between rhizobia and legume hosts, particularly soybeans. Our research demonstrates that genistein, an HH103 nod gene-inducing flavonoid, triggers hypervesiculation in this bacterium, which leads to a significant increase in the production of EVs transporting high molecular weight NFs. Interestingly, our findings indicate that adding these NF-loaded EVs not only promotes nodule primordia formation but also improves nodulation in soybean and in the model plant Lotus japonicus under controlled laboratory conditions. Notably, while EVs derived from non-induced cultures failed to enhance the number of nodules, they also exerted a positive effect on general plant growth parameters. Moreover, the application of NF-loaded EVs significantly increases soybean crop yield in field experiments, especially in the absence of water deficit. Conclusions: Results point to the role of these plant-growth-promoting vesicles in promoting legume yield. Therefore, our study proposes the use of rhizobial EVs as a sustainable agricultural strategy to optimize the rhizobium-legume symbiosis and boost crop productivity.Artículo N-Alkyl Isofagomine Lactams: Synthesis, Glycosidase Inhibition, and Antimicrobial Assessments(Georg Thieme Verlag KG, 2024-10-22) Moreń, Monika; Pereira Lourenço, Ana Laura; Cerdà-Cuéllar, Marta; Kochanowski, Karl; Jorgensen, Kåre B.; Sydnes, Magne O.; López López, Óscar; Lindbäck, Emil; Química Orgánica; European Union (UE); Ministerio de Ciencia e Innovación (MICIN). EspañaA series of six N-alkyl isofagomine lactam derivatives is synthesized over ten steps from d-arabinose. The compounds are evaluated as glycosidase inhibitors. It was found that the N-alkyl groups have a detrimental effect on the glycosidase inhibition activities, as the prepared N-alkyl isofagomine lactam derivatives are much less potent glycosidase inhibitors than native isofagomine lactam.Artículo Biocatalytic synthesis of heterobiaryl sulfoxides: a comparative study between Baeyer–Villiger monooxygenases and unspecific peroxygenases(Royal Society of Chemistry, 2026-02-26) Vázquez Domínguez, Pablo; Carrión-González, Julia; García-Requena, Desirée; Fraaije, Marco W.; Loncar, Nikola; Fernández Fernández, Rosario Fátima; Scheibner, Katrin; Gutiérrez, Ana; González-Benjumea, Alejandro; Ros Lao, Abel; Gonzalo Calvo, Gonzalo de; Química Orgánica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; European Union (UE); Ministerio de Ciencia e Innovación (MICIN). EspañaThe biocatalytic sulfoxidation of heterobiaryl indole- and pyrrole-based sulfides was investigated using unspecific peroxygenases (UPOs) and Baeyer–Villiger monooxygenases (BVMOs) as complementary oxidative biocatalysts. Among the UPOs tested, only the UPO from Marasmius rotula showed outstanding catalytic efficiency, reaching up to 99% conversion at substrate concentrations as high as 60 mM, with excellent chemoselectivity toward sulfoxides (>90%), albeit with moderate enantioselectivities (17–64% ee). In contrast, screening of a panel of BVMOs revealed superior stereochemical control: TmCHMO enabled the sulfoxidation of indole-based sulfides with enantioselectivities up to 94% ee, while OTEMO proved particularly effective for pyrrole-based substrates, affording sulfoxides in up to 90% ee. Reaction parameters such as temperature, pH, cosolvent and substrate loading have been optimized, allowing reaction rates of up to 22.4 mmol L−1 h−1 at 50 mM substrate concentration without enantioselectivity loss. Overall, pyrrole-based sulfides displayed higher optical purities than indole analogues under BVMO catalysis, whereas UPOs excelled in terms of productivity and operational simplicity. Selected BVMO- and UPO-catalyzed reactions were successfully scaled up, demonstrating the practical applicability of these biocatalytic systems. These results highlight the complementary strengths of UPOs and BVMOs for the efficient and selective synthesis of chiral heterobiaryl sulfoxides.Artículo Multicomponent Reaction for the Synthesis of β-Ketosulfides in Deep Eutectic Solvents(Multidisciplinary Digital Publishing Institute (MDPI), 2026-02-22) Falcini, Chiara; Jaén-Herrera, David; Fernández Fernández, Rosario Fátima; Alcántara, Andrés R.; Gonzalo Calvo, Gonzalo de; Química Orgánica; European Union (UE)The use of Type III Deep Eutectic Solvents (DESs) as both solvents and cocatalysts enable the one-pot synthesis of several β-ketosulfides, structural motifs commonly found in biologically active compounds, via a multicomponent reaction (MCR) involving 2-bromoketones, alkyl or benzyl halides, and potassium thioacetate in basic medium. Under these conditions, it was possible to avoid not only the use of the non-eco-friendly solvent dimethylformamide (DMF), but also an additional hydrolytic step previously reported for the preparation of these molecules. The MCR conducted in the presence of the DES ChCl:Gly (1:2) was optimized through the evaluation of different reaction parameters. Notably, the non-conventional medium could be recycled up to four times without any appreciable loss of catalytic activity. Environmental metrics, including the E factor, E+ factor, and Global Warming Potential (GWP), were calculated for the process both in the presence and absence of the DES, demonstrating improved environmental performance when the DES was employed.Artículo Biodegradable polyacrylamide-based hydrogels with unique bactericidal and osteoinductive properties to improve the clinical success of porous titanium implants(Elsevier, 2026-01) Martínez Muñoz, Guillermo; Castellano Pozo, Maikel; Merinero de los Santos, Manuel; Casado Jurado, David; Huertas Sánchez, Pablo; Pajuelo Domínguez, Eloísa; Miguel Rodríguez, Manuel de; Begines Ruiz, Belén; Torres Hernández, Yadir; Alcudia Cruz, Ana; Química Orgánica; Genética; Microbiología y Parasitología; Citología e Histología Normal y Patológica; Ingeniería y Ciencia de los Materiales y del Transporte; Química Orgánica y Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICIU). EspañaStress-shielding phenomenon, infections, and limited bone integration are traditional drawbacks associated with titanium implants. Biodegradable polyacrylamide-based hydrogels synthesized with an 8-fold scaled up, disulfide bond-containing crosslinker, were prepared to overcome these limitations. Hydrogels' biodegradability in the presence of glutathione has been demonstrated. Additionally, hydrogels exhibited strong antibacterial activity against pathogens such as P. aeruginosa and S. aureus, along with promising osseointegrative properties, in vitro fibroblast (CCL-1) viability, and in vivo biocompatibility in C. elegans. Porous titanium (Ti) fabricated via space-holder technique were infiltrated with previously described hydrogels. The optimal system, featuring a 4 wt% crosslinked acrylamide-based hydrogel infiltrated into 60 vol%, 355–500 μm Ti substrate, showed excellent biomechanical integrity and biofunctionality, supporting its potential as a safe and effective bone implant. Additionally, the study introduces streamlined, cost-effective methodologies for implant testing and characterization.Artículo Neutral sp2-iminosugars exploiting non-glycone interactions for selective acid α- and β-glucosidase activity modulation: Pharmacological chaperones for Gaucher and Pompe diseases(Elsevier, 2025-12-16) García Moreno, M. Isabel; Kawakami, Kiyoko; Nanba, Eiji; García Fernández, José M.; Higaki, Katsumi; Ortiz Mellet, Carmen; Química Orgánica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. EspañaA major challenge in developing selective active site-directed pharmacological chaperones for lysosomal storage disorders is discriminating among glycosidases acting on anomeric substrates. Here, we report the design and synthesis of neutral thiourea-type sp2-iminosugars derived from 1-deoxynojirimycin to rescue the activity of mutant variants of human acid β-glucosidase (GCase) and acid α-glucosidase (GAA) implicated in Gaucher disease (GD) and Pompe disease (PD), respectively. Structural diversification at the non-glycone substituents enabled fine-tuning of hydrophobic and π-stacking interactions, leading to selective enzyme targeting. In vitro assays and cell-based models demonstrated that aromatic derivatives restored GAA activity, improved autophagic flux, and normalized lysosomal trafficking in PD cells (HAP1-p.G549R cells), whereas aliphatic derivatives enhanced GCase activity and corrected mitochondrial dysfunction in GD fibroblasts (p.F213I and p.N370S fibroblasts). Notably, the N’-(p-methoxyphenyl)thiourea derivative exhibited dual activity, rescuing both GAA and GCase mutants without affecting wild-type enzymes. These results identify neutral thiourea-type sp2-iminosugars as promising scaffolds for next-generation pharmacological chaperones with enhanced selectivity and reduced off-target effects.Artículo Extending the Scope of the C-Functionalization of Cyclam via Copper(I)-Catalyzed Alkyne-Azide Cycloaddition to Bifunctional Chelators of Interest(ACS, 2024-04-11) Ollier, Cédric; Méndez Ardoy, Alejandro; Ortega Caballero, Fernando; Jiménez Blanco, José Luis; Le Bris, Nathalie; Tripier, Raphaël; Química Orgánica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. EspañaCyclam, known for its potent chelation properties, is explored for diverse applications through selective N-functionali-zation, offering versatile ligands for catalysis, medical research, and materials science. The challenges arising from N-alkylation, that could decrease the coordination properties, are addressed by intro-ducing a robust C-functionalization method. The facile two-step syn-thesis proposed here involves the click chemistry-based C-function-alization of a hydroxyethyl cyclam derivative using Cu(I)-catalyzed Alkyne-Azide Cycloaddition (CuAAC). Boc-protecting groups pre-vent undesired copper coordination, resulting in compounds with a wide range of functionalities. The optimized synthesis conditions en-able C-functional cyclams to be obtained easily and advantageously, with high application potential in the previously cited fields. The methodology has been extended to Trehalose-based Siamese twin amphiphiles, enabling efficient gene delivery applications.Artículo Exploring the influence of the glycone space on the therapeutic potential of sp2-iminoglycolipids(Elsevier, 2025) Padilla Pérez, María del Carmen; Rodríguez Marín, Rocío; González-Bakker, Aday; N. Khan, Adam; Bastardo-Torío, Mariana; Padrón, José M.; Sánchez Fernández, Elena Matilde; Ortiz Mellet, Carmen; Química Orgánica; Ministerio de Ciencia, Innovación y Universidades (MICIU). España; Agencia Estatal de Investigación. EspañaExtensive structure-activity relationship studies performed on sp2-iminoglycolipids revealed the fundamental role played by a linear dodecylsulfide/sulfonyl aglycone chain on the anticancer, antiparasitic and immunomodulatory activities. However, the influence of structural modifications within the glycone region on the therapeutic performance remains largely underexplored. To address this gap, we have designed and stereoselectively synthesized a novel series of sp2-iminoglycolipids incorporating targeted modifications to the glycomimetic unit. These include C2 deoxygenation, bioisosteric replacement of the hydroxyl group with fluorine, and selective installation of aromatic hydrocarbons at the O3 position. Among the synthesized compounds, the fluorinated derivative (1R)-2-deoxy-1-S-dodecyl-2-fluoro-3-O-(p-fluorobenzyl)-5N,6O-oxomethylidene-1-sulfonylnojirimycin emerged as a promising multi-target candidate. Live-cell imaging in human cervical cancer (HeLa) cells revealed phenotypic markers characteristic of apoptotic cell death. Furthermore, clonogenic assays showed a significant, concentration-dependent reduction in the formation of cancer cell colonies, indicating impairment of tumor cell reproductive viability. Altogether, these data support a potent antiproliferative activity. This compound also exhibited strong antiparasitic activity, effectively inhibiting the growth of Leishmania donovani amastigotes at low micromolar concentrations. Additionally, it showed notable anti-inflammatory properties in microglial cells by downregulating the NLRP3 inflammasome signaling pathway following inflammatory stimulation, as evidenced by reduced caspase-1 activation and suppressed IL-1β release.Artículo Isofagomine-coumarin hybrids: bridging cancer and Alzheimer's disease(Elsevier, 2025-08-05) Santos Evangelista, Teresa C.; González-Bakker, Aday; Puerta, Adrián; Poeta, Eleonora; Monti, Barbara; Naldi, Marina; Fernández-Bolaños Guzmán, José María; Lindbäck, Emil; López López, Óscar; López López, Óscar; Química Orgánica; Ministerio de Ciencia e Innovación (MICIN). España; European Union (UE); Junta de Andalucía; Universidad de SevillaGiven the urgent need for developing new therapeutic strategies against chronic diseases such as neurodegeneration and cancer, and the evidence of shared biochemical pathways linking Alzheimer’s disease to certain types of cancer, we have designed a novel family of multifaceted compounds to target both diseases. For that purpose, isofagomine (a relevant azasugar) – coumarin hybrids were prepared and tested in vitro as potential dual-action molecules. Key structural variations, including different hydroxyl group substitutions and changes in the length of the hydrocarbon linker, had minimal impact on cholinesterase inhibition. All compounds exhibited strong inhibition of butyrylcholinesterase (BuChE), representing the predominant cholinesterase in moderate-to-advanced stages of Alzheimer’s disease, with IC50 values in the single-digit micromolar concentration range. Additionally, the isofagomine-coumarin hybrids displayed remarkable selectivity, up to 177-fold, for human BuChE over human acetylcholinesterase (AChE). Docking simulations predicted derivatives to be accommodated within the BuChE binding region. Additionally, the compounds showed reduced neurotoxicity and moderate neuroprotection. Furthermore, a direct correlation was observed between tether length and antiproliferative activity, with the lead compound exhibiting potent effects in the low-micromolar range. 3D Holotomographic microscopy, through continuous live-cell imaging, proved mitotic arrest followed by apoptotic events to be involved in their mode of action. Azasugar-coumarin hybrids constitute promising multifaceted molecules in terms of therapeutics or prevention of neurodegeneration and cancer.Artículo Green One-Pot Synthesis of Benzimidazoles from Dinitroarenes in Water Using a Ru-Doped Co-Based Heterogeneous Catalyst(American Chemical Society, 2025-09-08) Río Rodríguez, José Luis del; Gutiérrez Tarriño, Silvia; Molina, María Asunción; Costley Wood, Lucy; Falcini, Chiara; Beale, Andrew M.; Oña Burgos, Pascual; Química Orgánica; Ministerio de Ciencia e Innovación (MICIN). España; European Union (UE); Generalitat ValencianaA novel methodology is presented for preparing non-noble metal-based heterogeneous catalysts doped with low amounts of noble metals, yielding highly active and reusable materials for sustainable organic transformations. A new Co–Ru@C catalyst was developed by incorporating small ruthenium nanoparticles (1 wt %) and cobalt nanoparticles (10 wt %) on Vulcan carbon via pyrolysis of a ruthenium-doped cobalt metal–organic framework supported on carbon (2D-Co(Ru)MOF/C). Advanced characterization (in situ PXRD and XAS, HAADF-STEM, HRTEM) confirmed strong Co–Ru interactions, enhancing catalytic activity. The catalyst was evaluated in the one-pot reductive amination of dinitrobenzenes to benzimidazoles using molecular hydrogen and water, which is in line with green chemistry. The synergistic effect between Co and Ru enabled quantitative product yields under significantly milder reaction conditions than the existing ones. In addition, ruthenium was found to facilitate hydrogen activation in the bimetallic material compared with its undoped Co@C counterpart. Regarding stability, the Co–Ru@C catalyst retained its activity over at least five consecutive cycles without metal leaching or structural degradation. This material demonstrated a broad substrate scope, affording over 20 functionalized benzimidazoles in high yields. Half-gram-scale syntheses of commercial Diabazole and Fuberidazole further validated the scalability of this approach.