Victoria Valdivia

Electrophilic isothiocyanates require a balance between target engagement, chemical persistence and physicochemical suitability. Here, a structurally constrained family of N-glycosyl iberin analogues was used to determine how oxidation of a C3 sulfur substituent modulates NRF2 activation without changing the position of the anomeric isothiocyanate group. The series comprises matched thioethers, sulfoxides and sulfones bearing methyl, phenyl or ethyl substituents. NRF2/ARE activity was quantified by reporter assay, solution stability was followed by time-dependent ¹H NMR in (CD₃)₂SO:D₂O (4:1), and drug-likeness was assessed using SwissADME. Thioethers 1β–3β were inactive within the tested range (CD > 30 μM), whereas sulfur oxidation restored NRF2 activity. The phenyl sulfoxide (R)-5β was the most potent member (CD = 1.55 ± 0.33 μM), while phenylsulfone 8β retained low-micromolar activity (CD = 2.09 ± 0.13 μM). This gain in potency was not accompanied by improved chemical stability. Time-dependent ¹H NMR showed complete degradation of thioethers 1β–3β by 24 h, while 8β reached complete degradation by 10 h. SwissADME analysis showed that the N-glycosyl series satisfied the Lipinski rule-of-five criteria, whereas polarity and flexibility remained the most restrictive bioavailability-radar dimensions. These results indicate that NRF2 potency does not follow a straightforward relationship with the sulfur oxidation state or kinetic stability, highlighting the need to integrate biological activity, direct stability measurements, and in silico profiling when prioritizing electrophilic glycomimetics.

Glucose-derived chiral auxiliaries were investigated as stereodivergent platforms for the preparation and transfer of a chiral CF₃SO fragment toward fluorinated sulforaphane (SFN) isosteres. DAG-derived trifluoromethanesulfinates showed a base-dependent reversal of stereochemical preference but limited chromatographic stability. The more robust DCG auxiliary enabled the isolation of both diastereomeric trifluoromethanesulfinates. Reactivity proved strongly nucleophile-dependent: Grignard reagents promoted double substitution at sulfur, whereas 3-azidopropoxide afforded enantioenriched 3-azidopropyl trifluoromethanesulfinates in 30–35% yield and 65–70% ee. Conversion of the azide into an isothiocyanate provided a CF₃-containing sulfinate isostere of SFN. These results establish glucose-derived trifluoromethanesulfinates as modular stereodivergent intermediates for fluorinated SFN analogues.

Carbohydrate-derived isothiocyanates are attractive glycomimetic redox modulators because the sugar scaffold can tune the chemical environment of the electrophilic N=C=S group. Two complementary families of S-glycosyl isothiocyanates bearing the ITC function at C3 or C6 of the glucopyranose ring were investigated to establish how ITC position influences NRF2 /ARE activation, solution stability and predicted ADME-related properties. The compounds vary in anomeric configuration, sulfur substituent, sulfur oxidation state and O-protection pattern. The C6-ITC family displayed the most consistently potent NRF2 activation, whereas the C3-ITC series showed a stronger dependence on sulfur oxidation and individual structural features. Time-dependent ¹H NMR studies in (CD₃)₂SO:D₂O (4:1) revealed marked structure-dependent differences in persistence. Within the C3 series, the β-phenylthioether was substantially more stable than its α anomer, while direct comparison of matched phenylsulfones showed a clear improvement in early persistence when the ITC group was moved from C3 to C6. Cheirolin was included as a natural sulfone benchmark. SwissADME analysis showed that matched C3/C6 regioisomers had nearly superimposable physicochemical profiles and identical Lipinski classification, whereas O-protection exerted a clearer influence on polarity and flexibility. These results identify ITC position, anomeric stereochemistry, sulfur chemistry and O-protection as complementary variables for balancing NRF2 activity, kinetic stability and predicted drug-like properties.

Isothiocyanates (ITCs) are well-known electrophilic agents with antioxidant and anticancer properties, largely attributed to their ability to activate the Nrf2/ARE pathway. Building on previous work with C1-ITC glycosyl derivatives, we designed and synthesized a new series of S-glycosyl isothiocyanates in which the ITC group was repositioned to the C6 carbon of the glucose scaffold. This structural rearrangement yielded stable and synthetically accessible derivatives with markedly enhanced biological profiles. Several compounds showed potent Nrf2 activation at non-cytotoxic concentrations, with CD values comparable to or exceeding those of natural ITCs. In parallel, the new C6-ITC derivatives displayed significant antiproliferative activity against leukemia and solid tumor cell lines. Among them, the phenylsulfone derivative 13 emerged as a particularly promising dual-action molecule, combining strong Nrf2 induction with low-micromolar cytotoxicity. Molecular docking was used as a hypothesis-generating approach and suggested a possible interaction with the STAT3 SH2 domain, although further studies are needed to validate this target. Overall, these results support glucose-based ITCs as a versatile platform for the development of multifunctional antioxidants with complementary anticancer properties.

The synthetic method developed for the preparation of NH ₂ /SO palladium complexes proved to be also an effective approach for N -desulfinylation. Furthermore, the Pd complexes demonstrated a higher trans influence of PhSO compared to ^t BuSO.

The preparation of new and functional nanostructures has received more attention in the scientific community in the past decade due to their wide application versatility. Among these nanostructures, micelles appear to be one of the most interesting supramolecular organizations for biomedical applications because of their ease of synthesis and reproducibility and their biocompatibility since they present an organization similar to the cell membrane. In this work, we developed micellar nanocarrier systems from surfactant molecules derived from oleic acid and tetraethylene glycol that were able to encapsulate and in vitro release the drug dexamethasone. In addition, the designed micelle precursors were able to functionalize metallic NPs, such as gold NPs and iron oxide NPs, resulting in monodispersed hybrid nanomaterials with high stability in aqueous media. Therefore, a new triazole-derived micelle precursor was developed as a versatile encapsulation system, opening the way for the preparation of new micellar nanocarrier platforms for drug delivery, magnetic resonance imaging, or computed tomography contrast agents for therapeutic and diagnostic applications.

En esta comunicación se expone el proceso de aplicación de un nuevo mo- delo de enseñanza-aprendizaje cuyo objetivo es incentivar el conocimiento de estereoquímica (la química en tres dimensiones) por parte de alumnos de primer curso del grado en Farmacia. Para ello, se diseñó un modelo metodológico y un mapa de contenidos que permitió obtener las preguntas clave o estructurantes del tema. Seguidamente, se diseñaron una serie de actividades para trabajar en grupo con el objetivo de incentivar a los estudiantes a comprender y aprender los puntos principales del tema. La evaluación del nivel de aprendizaje de los alum- nos se realizó mediante escaleras de aprendizaje, elaboradas a partir de un cues- tionario con las preguntas clave que los alumnos respondieron al inicio y al final de la aplicación del ciclo de mejora en el aula (CIMA) y que mostraron ser una herramienta útil tanto para conocer el nivel inicial de conocimiento de los alum- nos y sus obstáculos de aprendizaje, como para conocer su evolución después de realizar las actividades. Dicha evolución fue significativamente positiva en todos los casos. Finalmente, el 83% de los estudiantes valoró positivamente el CIMA en cuanto a su utilidad a la hora de trabajar, estudiar y comprender estereoquímica. Palabras clave: Química orgánica I, farmacia, docencia universitaria, desarro- llo profesional docente, estereoquímica.

Amphiphilic molecules have been actively explored as promising materials in the field of bio and nanotechnology. These molecules are constituted by a polar head and a lipophilic tail and in an aqueous medium are self-assemble to form different types of macromolecular structures such as micelles, monolayer vesicles, bars, sheets and tubes. In this work, a convergent synthetic approach for the synthesis of two new amphiphilic compounds based on a versatile amino polar head, a tetraethylene glycol spacer and a lipophilic tail derived from oleic acid has been developed. Subsequently, after a self-assembly process in aqueous medium, nanostructures as micelles have been obtained and characterized. Finally, a procedure for the inclusion of the highly lipophilic drug Dexamethasone has been carried out in order to study the ability of these micelles to act as nanovectors for drug delivery.