Artículos (Química Orgánica y Farmacéutica)

URI permanente para esta colecciónhttps://hdl.handle.net/11441/11085

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Lyocell/silver knitted fabrics for prospective diabetic foot ulcers treatment: Effect of knitting structure on bacteria and cell viability
(Elsevier, 2025-04-01) Tavares, Tânia D.; Ribeiro, Artur; Bengoechea Ruiz, Carlos; Rocha, Diana; Alcudia Cruz, Ana; Begines Ruiz, Belén; Silva, Carla Carolina; Antunes, Joana C.; Felgueiras, Helena P.; Universidad de Sevilla. Departamento de Ingeniería Química; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Fundación Nacional de Ciencia y Tecnología de Portugal (FCT)
Diabetic foot ulcers (DFUs) are a serious complication of diabetes, often resulting in infections and further health deterioration. Thus, the development of an approach combining different therapies in just one formulation to treat DFUs remains very challenging. Silver-plated polyamide fibers offer antimicrobial properties, while lyocell provides biodegradability, biocompatibility and moisture management abilities. In this sense, the present study explores the potential of lyocell/silver-plated polyamide fabrics as part of advanced wound dressings designed to improve DFU treatment. The most common knitting structures, namely single jersey, “false” rib 1 × 1, single pique, and “false” interlock, were selected for combining the yarns and successfully processed using seamless technology. The knitted fabrics were then subjected to a comprehensive analysis of their physical, chemical, and thermomechanical properties, demonstrating that the samples met the criteria for effective wound dressing development. Their antimicrobial efficacy was evaluated against DFU-associated Gram-negative pathogens, Escherichia coli and Pseudomonas aeruginosa, showing strong antimicrobial activity for up to 24 h, with total inhibition in some cases (jersey, pique and interlock structures for E. coli and interlock structure for P. aeruginosa). Antioxidant testing revealed DPPH reduction of 61.7 ± 14.4 %. Biocompatibility was assessed using keratinocytes HaCaT cell lines, showing that knitted fabrics with up to 1.46 % silver content did not harm mammalian cells. In general, interlock structure revealed the most promising features, including mechanical performance, and air and water vapor permeability, for promoting optimal wound healing conditions.
Hydrogels and Nanogels: Pioneering the Future of Advanced Drug Delivery Systems
(MDPI, 2025-02-07) Delgado-Pujol, Ernesto J.; Martínez Muñoz, Guillermo; Casado Jurado, David; Vázquez Cabello, Juan; León-Barberena, Jesús; Rodríguez Lucena, David; Torres Hernández, Yadir; Alcudia Cruz, Ana; Begines Ruiz, Belén; Universidad de Sevilla. Departamento de Ingeniería y Ciencia de los Materiales y del Transporte; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Universidad de Sevilla. Departamento de Química Orgánica; Ministerio de Ciencia e Innovación (MICIN). España; Universidad de Sevilla. TEP123: Metalurgia e Ingeniería de los Materiales; Universidad de Sevilla. FQM408: Química Farmacéutica Aplicada
Conventional drug delivery approaches, including tablets and capsules, often suffer from reduced therapeutic effectiveness, largely attributed to inadequate bioavailability and difficulties in ensuring patient adherence. These challenges have driven the development of advanced drug delivery systems (DDS), with hydrogels and especially nanogels emerging as promising materials to overcome these limitations. Hydrogels, with their biocompatibility, high water content, and stimuli-responsive properties, provide controlled and targeted drug release. This review explores the evolution, properties, and classifications of hydrogels versus nanogels and their applications in drug delivery, detailing synthesis methods, including chemical crosslinking, physical self-assembly, and advanced techniques such as microfluidics and 3D printing. It also examines drug-loading mechanisms (e.g., physical encapsulation and electrostatic interactions) and release strategies (e.g., diffusion, stimuli-responsive, and enzyme-triggered). These gels demonstrate significant advantages in addressing the limitations of traditional DDS, offering improved drug stability, sustained release, and high specificity. Their adaptability extends to various routes of administration, including topical, oral, and injectable forms, while emerging nanogels further enhance therapeutic targeting through nanoscale precision and stimuli responsiveness. Although hydrogels and nanogels have transformative potential in personalized medicine, challenges remain in scalable manufacturing, regulatory approval, and targeted delivery. Future strategies include integrating biosensors for real-time monitoring, developing dual-stimuli-responsive systems, and optimizing surface functionalization for specificity. These advancements aim to establish hydrogels and nanogels as cornerstones of next-generation therapeutic solutions, revolutionizing drug delivery, and paving the way for innovative, patient-centered treatments.
Enhanced porous titanium biofunctionalization based on novel silver nanoparticles and nanohydroxyapatite chitosan coatings
(Elsevier, 2025-04) Castillejo, Ana; Martínez Muñoz, Guillermo; Delgado-Pujol, Ernesto J.; Villalobo Polo, Eduardo; Carrillo de la Fuente, Francisco; Casado Jurado, David; Pérez Bernal, Juan Luis; Begines Ruiz, Belén; Torres Hernández, Yadir; Alcudia Cruz, Ana; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Universidad de Sevilla. Departamento de Ingeniería y Ciencia de los Materiales y del Transporte; Universidad de Sevilla. Departamento de Química Analítica; Universidad de Sevilla. Departamento de Ingeniería Química; Universidad de Sevilla. Departamento de Microbiología; Ministerio de Ciencia e Innovación (MICIN). España
Titanium is widely used for implants however it presents limitations such as infection risk, stress shielding phenomenon, and poor osseointegration. To address these issues, a novel approach was proposed that involves fabricating porous titanium substrates, to reduce implant stiffness, minimizing stress shielding and bone resorption, and applying polymeric coatings to improve bioactivity. Composite coating prepared from chitosan, silver nanoparticles, and nanohydroxyapatite was optimized to enhance antibacterial properties and promote osseointegration. Chitosan with 80.5 % of deacetylation degree was used to prepare composites with diverse compositions, including different methodologies of adding silver nanoparticles, with silver concentrations below toxic level. Antibacterial activity was tested with three different strains, including Gram+ and Gram− bacteria, demonstrating excellent inhibition after 21 days. In addition, the induction of hydroxyapatite formation was investigated. Finally, the optimal porous metallic substrate that exhibited a more suitable stiffness (29 GPa) (close to the cortical bone tissue they intend to replace) was chosen to be infiltrated with the selected composites. In summary, this synergistic approach based on the combination of porous titanium substrates with 60 vol% porosity and a 355–500 μm pore size distribution coated with 3%CS-nHA-AgNPs-TPP-AgNPsbath composite provided a potential solution to provide implants with improved biomechanical balance and biofunctionality.
Immunomodulatory Effects and Regulatory Mechanisms of (R)-6-HITC, an Isothiocyanate from Wasabi (Eutrema japonicum), in an Ex Vivo Mouse Model of LPS-Induced Inflammation
(American Chemical Society, 2024-09-19) Alcarranza Saucedo, Manuel; Alarcón de la Lastra Romero, Catalina; Recio Jiménez, Rocío; Fernández Fernández, Inmaculada; Castejón Martínez, María Luisa; Villegas Lama, Isabel; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Junta de Andalucía
The present study aimed to investigate the effects of (R)-(−)-1-isothiocyanato-6-(methylsulfinyl)-hexane [(R)-6-HITC], the major isothiocyanate present in wasabi, in an ex vivo model of inflammation using lipopolysaccharide-stimulated murine peritoneal macrophages. (R)-6-HITC improved the immune response and mitigated oxidative stress, which involved suppression of reactive oxygen species, nitric oxide, and pro-inflammatory cytokines (IL-1β, IL-6, IL-17, IL-18, and TNF-α) production and downregulation of pro-inflammatory enzymes such as inducible nitric oxide synthase, COX-2, and mPGES-1. In addition, (R)-6-HITC was able to activate the Nrf2/HO-1 axis while simultaneously inhibiting key signaling pathways, including JAK2/STAT3, mitogen-activated protein kinases, and canonical and noncanonical inflammasome pathways, orchestrating its potent immunomodulatory effects. Collectively, these findings demonstrate the potential of (R)-6-HITC as a promising nutraceutical for the management of immuno-inflammatory diseases and justify the need for further in vivo validation studies.
Isoprenyl-thiourea and urea derivatives as new farnesyl diphosphate analogues: Synthesis and in vitro antimicrobial and cytotoxic activities
(2012) Vega Pérez, José Manuel; Argandoña Bertrán, Montserrat; Vega Holm, Margarita; Periñán, Ignacio; Palo Nieto, Carlos; Burgos Morón, Estefanía; López Lázaro, Miguel; Vargas Macías, Carmen; Nieto Gutiérrez, Joaquín José; Iglesias Guerra, Fernando; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Universidad de Sevilla. Departamento de Microbiología y Parasitología; Universidad de Sevilla. Departamento de Farmacología; Junta de Andalucía; Ministerio de Educación y Ciencia (MEC). España; Ministerio de Asuntos Exteriores y Cooperación. España
A series of new isoprenyl-thiourea and urea derivatives were synthesized by the reaction of alkyl or aryl isothiocyanate or isocyanate and primary amines. The structures of the compounds were established by 1H NMR, 13C NMR, MS, HRMS and elemental analysis. The new compounds were screened for in vitro antimicrobial activity against seven strains representing different types of gram-positive and gram-negative bacteria. More than a third of the synthesized compounds showed variable inhibition activities against the tested strains. Best antimicrobial activities were found for those thiourea analogues with 3-methyl-2-butenyl, isobutyl or isopentyl groups and aromatic rings possessing electron withdrawing substituents. The new compounds were also subjected to a preliminary screening for antitumoral activity. The presence of a highly lipophilic group and an electron withdrawing group in the aromatic rings enhanced anticancer activity of the synthesized compounds, showing in most cases more activity than that of the controls.
Aziridines from alkenyl-β-D-galactopyranoside derivatives: Stereoselective synthesis and in vitro selective anticancer activity
(Elsevier, 2013-12) Vega Pérez, José Manuel; Palo Nieto, Carlos; Vega Holm, Margarita; Góngora Vargas, Purificación; Calderón Montaño, José Manuel; Calderón Montaño, José Manuel; Burgos Morón, Estefanía; López Lázaro, Miguel; Iglesias Guerra, Fernando; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Junta de Andalucía; Ministerio de Asuntos Exteriores y Cooperación. España
A series of new aziridines β-D-galactopyranoside derivatives were synthesized from alkenyl β-D-galactopyranosides employing Sharpless conditions. The structures of the compounds were established by 1H NMR, 13C NMR, MS, HRMS and elemental analysis. The stereoselectivity of the reaction and the structural requirements of the alkenyl precursor for improving diastereoisomeric excesses of the direct aziridination reaction were also studied. The new compounds were subjected to a preliminary screening for cytotoxic activity against human lung cancer cells vs. human non-malignant lung cells. Terminal aziridine derivatives showed activity and, most notably, selectivity. One of the most active and selective compounds was also evaluated against breast cancer cells, melanoma cells, and non-malignant cells from the same origin. Its cytotoxic activity was similar to that of the positive controls, displaying a highly selective cytotoxic activity against both types of cancer cells.
Selective cytotoxic activity of new lipophilic hydroxytyrosol alkyl ether derivatives
(American Chemical Society, 2013-05-02) Calderón Montaño, José Manuel; Madrona, Andrés; Burgos Morón, Estefanía; Orta Vázquez, Manuel Luis; Mateos Cordero, Santiago; Espartero Sánchez, José Luis; López Lázaro, Miguel; Universidad de Sevilla. Departamento de Farmacología; Universidad de Sevilla. Departamento de Biología Celular; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Junta de Andalucía
Recent data suggest that hydroxytyrosol, a phenolic compound of virgin olive oils, has anticancer activity. This communication reports the synthesis of decyl and hexadecyl hydroxytyrosyl ethers, as well as the cytotoxic activity of hydroxytyrosol and a series of seven hydroxytyrosol alkyl ether derivatives against A549 lung cancer cells and MRC5 non-malignant lung fibroblasts. Hydroxytyrosyl dodecyl ether (HTDE) showed the highest selective cytotoxicity, and possible mechanisms of action were investigated; results suggest that HTDE can moderately inhibit glycolysis, induce oxidative stress, and cause DNA damage in A549 cells. The combination of HTDE with the anticancer drug 5-fluorouracil induced a synergistic cytotoxicity in A549 cancer cells but not in non-malignant MRC5 cells. HTDE also displayed selective cytotoxicity against MCF7 breast cancer cells versus MCF10 normal breast epithelial cells in the 1-30 μM range. These results suggest that the cytotoxicity of HTDE is more potent and selective than that of parent compound hydroxytyrosol.
Efficient Strategy to Synthesize Tunable pH-Responsive Hybrid Micelles Based on Iron Oxide and Gold Nanoparticles
(American Chemical Society, 2024) Gimeno Ferrero, Raúl; Rodríguez de Jesús, Javier; Pernia Leal, Manuel; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Junta de Andalucía
The preparation of multifunctional nanomaterials based on inorganic nanoparticles with organic materials has emerged as a promising strategy for the development of new nanomedicines for in vitro and in vivo biomedical applications. Here, we synthesized pH-responsive hybrid inorganic micelles by combining a novel pH-responsive amphiphilic molecule with hydrophobic payloads. This amphiphile was synthesized in a one-pot reaction and self-assembled readily into micelles under acidic pH conditions. In the presence of hydrophobic NP payloads such as AuNPs or IONPs, the amphiphile self-organized around them through hydrophobic interactions, resulting in the formation of colloidally stable hybrid micelles. The size of the hydrophobic NPs determined the pH-response of the inorganic hybrid micelles, which is tuned from pH 7 to 11 for our pH-responsive amphiphilic molecule. This achievement represents a novel approach for the synthesis of tunable pH-responsive hybrid micelles based on inorganic NPs for biomedical imaging, hyperthermia treatment, and also drug delivery nanosystems.
Findings and perspectives of β-Ti alloys with biomedical applications: Exploring beyond biomechanical and biofunctional behaviour
(Elsevier, 2024-12) Elhadad, Amir A.; Romero-Resendiz, Liliana; Rossi, Mariana Correa; Rodríguez-Albelo, Luisa Marleny; Lascano, Sheila; Afonso, Conrado R.M.; Alcudia Cruz, Ana; Amigó, Vicente; Torres Hernández, Yadir; Universidad de Sevilla. Departamento de Ingeniería y Ciencia de los Materiales y del Transporte; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Ministerio de Ciencia e Innovación (MICIN). España; Universidad de Sevilla. FQM: 408: Química Farmacéutica Aplicada; Universidad de Sevilla. TEP123: Metalurgia e Ingeniería de los Materiales
Early implant failure and bone resorption may occur in load-bearing conditions as a result of stress shielding brought on by a mismatch in the bone-Ti-implant modulus. A review with a novel multidisciplinary perspective is proposed in this work, which considers recent developments of β-Titanium alloys and new trends in novel microstructures, processing techniques, properties of dense and porous substrates, as well as the relationship between all these aspects and performance in service, in terms of improved its biomechanical and bio-functional balance. In addition to highlighting several modern and historical uses for Ti alloys, this review covers many cutting-edge novel β-Ti alloys and uses that promise to exceed historical standards. Also, it deepens through several important properties of these alloys, including toxicity of alloying elements, phase stability, thermo-mechanical processing, heat treatment, surface, and stress-induced modifications. The stiffness, hardness, fatigue and wear resistance, corrosion behaviour, biocompatibility, and manufacturing and surface modification effects on these parameters are also emphasized. In-vitro and in-vivo assays have been added to highlight important aspects of bioactivity and antibacterial behaviour, and future significant research areas are suggested along with new techniques to ensure the successful clinical application of β-Ti alloys.
Unraveling the Formation of Ternary AgCuSe Crystalline Nanophases and Their Potential as Antibacterial Agents
(American Chemical Society, 2024-10-09) Lin, Mengxi; Estruch Blasco, Manel; Pernia Leal, Manuel; Pajuelo Domínguez, Eloísa; Rodríguez, Laura; Figuerola, Albert; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Universidad de Sevilla. Departamento de Microbiología y Parasitología; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Dutch Research Council (NWO); Generalitat de Catalunya; Junta de Andalucía; Universidad de Sevilla
AgCuSe nanoparticles could contribute to the growth of strongly light-absorbing thin films and solids with fast ion mobility, among other potential properties. Nevertheless, few methods have been developed so far for the synthesis of AgCuSe nanoparticles, and those reported deliver nanostructures with relatively large sizes and broad size and shape distributions. In this work, a colloidal cation exchange method is established for the easy synthesis of AgCuSe NPs with ca. 8 nm diameters and narrow size dispersion. Notably, in this lower size range the conucleation and growth of two stoichiometric ternary compounds are generally observed, namely the well-known eucairite AgCuSe compound and the novel fischesserite-like Ag3CuSe2 phase, the latter being less thermodynamically stable as predicted computationally and assessed experimentally. An optimal range of Cu/Ag precursor molar ratio has been identified to ensure the growth of ternary nanoparticles and, more specifically, that of the metastable Ag3CuSe2 nanophase isolated for the first occasion. The attained size range for the material paves the way for utilizing AgCuSe nanoparticles in new ways within the field of biomedicine: the results obtained here confirm the antibacterial activity of the new AgxCuySez nanoparticles against Gram-positive bacteria, with significantly low values of the minimal inhibitory concentration. © 2024 The Authors. Published by American Chemical Society.
Engineering amphiphilic alkenyl lipids for self-assembly in functional hybrid nanostructures
(Springer Nature, 2024-11-21) Gimeno Ferrero, Raúl; Valdivia Giménez, Victoria Esther; Fernández Fernández, Inmaculada; García-Martín, María Luisa; Pernia Leal, Manuel; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Junta de Andalucía
The development of biocompatible hybrid nanosystems for advanced functional applications presents significant challenges to the research community. Key obstacles include the poor solubility of these nanosystems in water and the difficulty of precisely controlling their nanostructure dimensions and composition. A promising approach to overcoming these challenges is the self-assembly of surfactant-based building blocks into well-ordered hybrid nanostructures. In this study, we explore the relationship between structure and self-assembly in novel low molecular weight amphiphilic molecules to produce stable and biocompatible hybrid nanostructures. We investigated the self-assembly behavior of two families of amphiphiles derived from alkenyl lipids with one or two double bonds, leading to distinct hybrid supramolecular structures facilitated by the incorporation of hydrophobic iron oxide nanoparticles (IONPs) as templates. The presence of double bonds in the lipid tail and the morphology of the amphiphile influence the arrangement on the hydrophobic NPs. Amphiphiles with a single double bond in the lipid tail form highly water-soluble, well-ordered micellar-like structures on the IONP surfaces, while those with two double bonds create disordered lipid nanoparticles. Furthermore, these amphiphilic molecules can self-organize into higher-order hybrid supramolecular structures, such as vesicles, with potential applications in magnetic resonance imaging (MRI).
Properties of polyplexes formed between a cationic polymer derived from l-arabinitol and nucleic acids
(Royal Society of Chemistry, 2021-05-14) Pérez Alfonso, David; López López, Manuel; López-Cornejo, María del Pilar; Romero Azogil, Lucía; Benito Hernández, Elena María; García Martín, María de Gracia; García Calderón, Clara Beatriz; Valle Rosado, Iván; Romero Balestra, Fernando; Huertas Sánchez, Pablo; García Calderón, Margarita; Moyá Morán, María Luisa; Universidad de Sevilla. Departamento de Química Física; Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Universidad de Sevilla. Departamento de Genética; Junta de Andalucía; Universidad de Sevilla; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; European Union (UE)
In this work a sugar-based cationic polymer derived from L-arabinitol, PUArab, was prepared and its interactions with the linear calf thymus DNA and with the circular plasmid pEGFP-C1 were investigated at different N/P ratios. The polyplexes were characterized by using several techniques. For both nucleic acids, a charge inversion was observed, together with a conformational change from a coiled structure to a more compacted one. However, the N/P ratio required to observe the DNA condensation depended on the nucleic acid architecture. PUArab presents low toxicity in several cell lines. The transfection efficiency, TE, of the PUArab/pEGFP-C1 polyplexes was investigated at several N/P ratios in order to study their potential as vectors in gene transfection.
Stereoselective Synthesis of Chiral C2-Symmetric 1,3- and 1,5-Bis-Sulfoxides Guided by the Horeau Principle: Understanding the Influence of the Carbon Chain Nature in Its Ability for Metal Coordination
(ACS Publications, 2024-10-02) Moreno Rodríguez, Nazaret; Prieto Ramírez, Luis Alberto; Valdivia Giménez, Victoria Esther; Recio Jiménez, Rocío; Fernández Fernández, Inmaculada; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; European Union (UE); Junta de Andalucía; Ministerio de Ciencia, Innovación y Universidades (MICINN). España
The stereoselective synthesis of two distinct types of C2-symmetric chiral bis-sulfoxides, 1,3- and 1,5-bis(sulfinyl) derivatives, has been achieved based on the DAG methodology. The 1,5-bis(sulfinyl) derivatives constitute a new family of tridentate chiral ligands thanks to the presence of an additional sulfenyl or sulfinyl group in the carbon chain acting as a bridge. A systematic development and optimization of two synthetic routes, one for each ligand family, have been undertaken, highlighting the strategic utilization of Horeau’s law to enhance enantioselectivity. Additionally, palladium (Pd) and ruthenium (Ru) complexes derived from the synthesized bis-sulfoxides were prepared, and their structures were elucidated through spectroscopic analysis. Isolation of Pd(II) complexes involving 1,3-bis-sulfoxides was exclusively achieved using trifluoroacetates as coligands. In the case of Ru(II) complexes, the trans geometry could be determined for 1,3-bis-sulfoxides. The introduction of a third sulfur atom as a coordinating element in the 1,5-bis(sulfinyl) derivatives facilitates the formation of two distinct tricoordinated Ru(II) complexes. The structure of these complexes is intricately influenced by the oxidation state adopted by the central sulfur on the chain, whether as a thioether or as a sulfoxide.
Advanced interpenetrating polymer networks for innovative gastroretentive formulations targeting Helicobacter pylori gastric colonization
(Elsevier, 2024-09) Grosso, Roberto; Benito Hernández, Elena María; Carbajo Gordillo, Ana Isabel; Díaz, Manuel Jesús; García Martín, María de Gracia; Paz Báñez, María Violante de; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Agencia Estatal de Investigación. España; European Union (UE); Junta de Andalucía
The escalating challenges of Helicobacter pylori-induced gastric complications, driven by rising antibiotic resistance and persistent cancer risks, underscore the demand for innovative therapeutic strategies. This study addresses this urgency through the development of tailored semi-interpenetrating polymer networks (semi-IPN) serving as gastroretentive matrices for amoxicillin (AMOX). They are biodegradable, absorb significant volume of simulated gastric fluid (swelling index > 360 %) and exhibit superporous microstructures, remarkable mucoadhesion, and buoyancy. The investigation includes assessment at pH 1.2 for comparative analysis with prior studies and, notably, at pH 5.0, reflecting the acidic environment in H. pylori-infected stomachs. The semi-IPN demonstrated gel-like structures, maintaining integrity throughout the 24-hour controlled release study, and disintegrating upon completing their intended function. Evaluated in gastroretentive drug delivery system performance, AMOX release at pH 1.2 and pH 5.0 over 24 h (10 %-100 %) employed experimental design methodology, elucidating dominant release mechanisms. Their mucoadhesive, buoyant, three-dimensional scaffold stability, and gastric biodegradability make them ideal for accommodating substantial AMOX quantities. Furthermore, exploring the inclusion of the potassium-competitive acid blocker (P-CAB) vonoprazan (VONO) in AMOX-loaded formulations shows promise for precise and effective drug delivery. This innovative approach has the potential to combat H. pylori infections, thereby preventing the gastric cancer induced by this pathogen.
Simultaneous Formation of Polyhydroxyurethanes and Multicomponent Semi-IPN Hydrogels
(MDPI, 2024) Carbajo Gordillo, Ana Isabel; Benito Hernández, Elena María; Galbis Fuster, Elsa; Grosso, R.; Iglesias Blanco, Nieves; Valencia, C.; Lucas Rodríguez, Ricardo; García Martín, María de Gracia; Paz Báñez, María Violante de; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Ministerio de Ciencia, Innovación y Universidades (MICINN). España; Junta de Andalucía
This study introduces an efficient strategy for synthesizing polyhydroxyurethane-based multicomponent hydrogels with enhanced rheological properties. In a single-step process, 3D materials composed of Polymer 1 (PHU) and Polymer 2 (PVA or gelatin) were produced. Polymer 1, a crosslinked polyhydroxyurethane (PHU), grew within a colloidal solution of Polymer 2, forming an interconnected network. The synthesis of Polymer 1 utilized a Non-Isocyanate Polyurethane (NIPU) methodology based on the aminolysis of bis(cyclic carbonate) (bisCC) monomers derived from 1-thioglycerol and 1,2-dithioglycerol (monomers A and E, respectively). This method, applied for the first time in Semi-Interpenetrating Network (SIPN) formation, demonstrated exceptional orthogonality since the functional groups in Polymer 2 do not interfere with Polymer 1 formation. Optimizing PHU formation involved a 20-trial methodology, identifying influential variables such as polymer concentration, temperature, solvent (an aprotic and a protic solvent), and the organo-catalyst used [a thiourea derivative (TU) and 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU)]. The highest molecular weights were achieved under near-bulk polymerization conditions using TU-protic and DBU-aprotic as catalyst–solvent combinations. Monomer E-based PHU exhibited higher (Formula presented.) than monomer A-based PHU (34.1 kDa and 16.4 kDa, respectively). Applying the enhanced methodology to prepare 10 multicomponent hydrogels using PVA or gelatin as the polymer scaffold revealed superior rheological properties in PVA-based hydrogels, exhibiting solid-like gel behavior. Incorporating monomer E enhanced mechanical properties and elasticity (with loss tangent values of 0.09 and 0.14). SEM images unveiled distinct microstructures, including a sponge-like pattern in certain PVA-based hydrogels when monomer A was chosen, indicating the formation of highly superporous interpenetrated materials. In summary, this innovative approach presents a versatile methodology for obtaining advanced hydrogel-based systems with potential applications in various biomedical fields.
Synthesis of a New β-Galactosidase Inhibitor Displaying Pharmacological Chaperone Properties for GM1 Gangliosidosis
(MDPI, 2022) Clemente, Francesca; Martínez Bailén, Macarena; Matassini, Camilla; Morrone, Amelia; Falliano, Silvia; Caciotti, Anna; Paoli, Paolo; Goti, Andrea; Cardona, Francesca; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica
GM1 gangliosidosis is a rare lysosomal disease caused by the deficiency of the enzyme β-galactosidase (β-Gal; GLB1; E.C. 3.2.1.23), responsible for the hydrolysis of terminal β-galactosyl residues from GM1 ganglioside, glycoproteins, and glycosaminoglycans, such as keratan-sulfate. With the aim of identifying new pharmacological chaperones for GM1 gangliosidosis, the synthesis of five new trihydroxypiperidine iminosugars is reported in this work. The target compounds feature a pentyl alkyl chain in different positions of the piperidine ring and different absolute configurations of the alkyl chain at C-2 and the hydroxy group at C-3. The organometallic addition of a Grignard reagent onto a carbohydrate-derived nitrone in the presence or absence of a suitable Lewis Acid was exploited, providing structural diversity at C-2, followed by the ring-closure reductive amination step. An oxidation-reduction process allowed access to a different configuration at C-3. The N-pentyl trihydroxypiperidine iminosugar was also synthesized for the purpose of comparison. The biological evaluation of the newly synthesized compounds was performed on leucocyte extracts from healthy donors and identified two suitable β-Gal inhibitors, namely compounds 10 and 12. Among these, compound 12 showed chaperoning properties since it enhanced β-Gal activity by 40% when tested on GM1 patients bearing the p.Ile51Asn/p.Arg201His mutations.
GCase Enhancers: A Potential Therapeutic Option for Gaucher Disease and Other Neurological Disorders
(MDPI, 2022) Martínez Bailén, Macarena; Clemente, Francesca; Matassini, Camilla; Cardona, Francesca; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica
Pharmaceutical chaperones (PCs) are small compounds able to bind and stabilize misfolded proteins, allowing them to recover their native folding and thus their biological activity. In particular, lysosomal storage disorders (LSDs), a class of metabolic disorders due to genetic mutations that result in misfolded lysosomal enzymes, can strongly benefit from the use of PCs able to facilitate their translocation to the lysosomes. This results in a recovery of their catalytic activity. No PC for the GCase enzyme (lysosomal acid-β-glucosidase, or glucocerebrosidase) has reached the market yet, despite the importance of this enzyme not only for Gaucher disease, the most common LSD, but also for neurological disorders, such as Parkinson’s disease. This review aims to describe the efforts made by the scientific community in the last 7 years (since 2015) in order to identify new PCs for the GCase enzyme, which have been mainly identified among glycomimetic-based compounds.
Uso de herramientas activas para dinamizar el aula y mejorar el aprendizaje en la asignatura de Química Orgánica I
(Real e Ilustre Colegio Oficial de Farmacéuticos de Sevilla, 2023) Moreno Rodríguez, Nazaret; Valdivia Giménez, Victoria Esther; Recio Jiménez, Rocío; Vega Holm, Margarita; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica
El absentismo estudiantil, la dificultad para mantener la atención en clase y la falta de organización del trabajo diario fuera del aula son tres de los problemas más importantes a los que se enfrenta el profesorado universitario, sobre todo en asignaturas de los primeros cursos, consideradas por el alumnado como difíciles, como es el caso de la asignatura de Química Orgánica I (QOI) del Grado en Farmacia. En este trabajo se propone incentivar la atención de los estudiantes empleando la plataforma wooclap durante las clases teórico-prácticas de la asignatura de QOI y la mejora del trabajo individual de los alumnos fuera del aula mediante la realización de cuestionarios a través de Blackboard Collaborate ultra. Ambas propuestas pretenden mejorar la calidad del aprendizaje y fomentar la elección por parte del alumnado de la evaluación continua, contribuyendo a disminuir la tasa de suspensos y no presentados que caracteriza a la asignatura. Además, se presenta un modelo de evaluación de la utilidad de la propuesta de innovación planteada a través de un cuestionario anónimo, permitiendo la identificación de las principales fortalezas y debilidades del modelo aplicado y pudiéndose llevar a cabo ciclos de mejora.
Chemically Tuning Resveratrol for the Effective Killing of Gram- Positive Pathogens
(ACS, 2022) Cebrián, Rubén; Li, Qian; Peñalver, Pablo; Belmonte Reche, Efres; Andrés Bilbao, María; Lucas Rodríguez, Ricardo; Paz Báñez, María Violante de; Kuipers, Oscar P.; Morales, Juan Carlos; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Junta de Andalucía; Dutch Research Council
In the era of antimicrobial resistance, the identification of new compounds with strong antimicrobial activity and the development of alternative therapies to fight drug-resistant bacteria are urgently needed. Here, we have used resveratrol, a safe and well-known plant-derived stilbene with poor antimicrobial properties, as a scaffold to design several new families of antimicrobials by adding different chemical entities at specific positions. We have characterized the mode of action of the most active compounds prepared and have examined their synergistic antibacterial activity in combination with traditional antibiotics. Some alkyl- and silyl-resveratrol derivatives show bactericidal activity against Gram-positive bacteria in the same low micromolar range of traditional antibiotics, with an original mechanism of action that combines membrane permeability activity with ionophore-related activities. No cross-resistance or antagonistic effect was observed with traditional antibiotics. Synergism was observed for some specific general-use antibiotics, such as aminoglycosides and cationic antimicrobial peptide antibiotics. No hemolytic activity was observed at the active concentrations or above, although some low toxicity against an MRC-5 cell line was noted.
Chitosan-based hydrogels obtained via photoinitiated click polymer IPN reaction
(Elsevier, 2023-06) Sánchez Cid, Pablo; Romero García, Alberto; Paz Báñez, María Violante de; Pérez-Puyana, Víctor Manuel; Universidad de Sevilla. Departamento de Ingeniería Química; Universidad de Sevilla. Departamento de Química Orgánica y Farmacéutica; Universidad de Sevilla. Departamento de Ingeniería Química y Ambiental; Ministerio de Ciencia e Innovación (MICIN). España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Junta de Andalucía; Universidad de Sevilla. TEP229: Tecnología y Diseño de Productos Multicomponentes; Universidad de Sevilla. FQM135: Carbohidratos y Polímeros
Chitosan (CTS) is a polysaccharide with a wide variety of applications in the biomedical field, owing to its outstanding disinfectant properties, biocompatibility and biodegradability, but with limited mechanical properties. The proposed strategy to improve CTS-based hydrogel properties in this study is the formation of a semi-interpenetrating polymer network (semi-IPN). In this way, a photo-initiated radical click reaction was proposed to obtain a synthetic polymer, whose components were included in a CTS solution, resulting in the semi-IPN network after UV illumination. Different crosslinking degrees (CD) and CTS/polymer ratios were evaluated through rheological characterization, along with an assessment of both variables based on an experimental model design, obtaining that, for every CTS/polymer ratio, intermediate values of CD (8 %) offered the best rheological properties. In addition, chemical and microstructural characterization were carried out for selected hydrogels, obtaining consistent results according to rheological characterization, as the 1/1 CTS/polymer ratio with CD 8 % hydrogel displayed the most homogeneous pore size and distribution, consequently leading to the best rheological performance.

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