Susana Rincón

Triazole hybrids have emerged as versatile scaffolds exhibiting diverse pharmacological profiles. In this study, four novel xanthine steroid hybrids linked via a 1,2,3‐triazole moiety ( 4–7 ) were efficiently synthesized through copper(I)‐catalyzed azide alkyne cycloaddition. Their bioactive potential was investigated using molecular docking and in vitro assays targeting both metabolic and apoptotic pathways. Docking simulations were performed against the anti‐apoptotic protein BCL‐2 (isoform 1), associated with human breast adenocarcinoma cells, and α‐glucosidase, a key enzyme involved in carbohydrate hydrolysis. Among the series, compound 4 displayed the highest binding affinity toward α‐glucosidase and significant affinity toward BCL‐2. In vitro assays confirmed that compound 4 exhibited the most potent dual effect, demonstrating α‐glucosidase inhibition with an IC ₅₀ value of 123.9 µM (95% CI: 119–129 µM) and an antiproliferative effect on MCF‐7 cells, reaching a maximum viability reduction of 21% ± 3% at 250 µM. The dual activity is largely attributed to the 1,2,3‐triazole linker, which facilitates stacking and critical hydrogen‐bonding interactions with its biological targets.

The formation of 1,2,3-triazoles by Cu(I)-catalyzed reactions is a methodology that has been recurrently employed to obtain new hybrid organic compounds that by themselves exhibit biological activity. It has been observed that the presence of triazoles as a bridge between two different organic compounds increases the biological activity. In this work we report the obtention of a 1,2,3-triazole 1,4-disubstituted hybrid 1,2,3-triazole from ethinylestradiol and a theobromine azide with the aim of obtaining a prominent compound with activity against α-glucosidasa, since molecular docking was performed obtaining a better affinity compared to acarbose.

Steroids are an important class of biologically active polycyclic compounds and have been widely used for various therapeutic purposes. Ethinylestradiol is used as a hormone regulator and its derivatives have been used as antitumor agents. This paper describes the development of a new hybrid with potential inhibitory activity against α‐glucosidase. This new hybrid, 1,2,3‐triazole ethinylestradiol‐theobromine 6, was synthesized using a classic CuAAC reaction between a theophylline‐derived azide and ethinylestradiol. A prediction study analyzed through molecular docking showed that compound 6 exhibited a stronger binding affinity with α‐glucosidase compared to commercial acarbose (ΔG ‐8.2 vs. ‐10.9).

Objective: The present contribution describes a novel approach for obtaining steroid derivatives of the iso-type from sapogenins for drug discovery. Methodology: Diastereomeric 23-acetyl-spirostanols were prepared by acetolysis of smilagenin (4) (25 R) using boron trifluoride diethyl etherate in acetic anhydride followed by treatment of the epimeric epoxycholestene obtained (6 or 9) under basic hydrolysis. Higher regioselectivity was attained in the presence of ZnCl₂ in acetic anhydride. Results: Acetolysis of smilagenin (4) (25 R) using boron trifluoride diethyl etherate in acetic anhydride afforded 20-α-methyl epoxycholestene 6 as the major product, two furostene derivatives ( 7 and 8), as well as the new 20-β-methyl epoxycholestene 9. Increased regioselectivity for the acetolysis of smilagenin (4) was observed using ZnCl₂ in acetic anhydride affording 6 in 90% yield. Subsequent treatment of the epimeric epoxycholestene (6 or 9) under basic hydrolysis afforded two new diastereomeric 23-acetyl-spirostanols 14 and 15. The structures of all compounds were established using 1D and 2D NMR techniques. Conclusions: Formation of the two diastereomeric 23-acetyl-spirostanols (14 and 15) from epimeric epoxycholestenes 6 and 9 with KOH/EtOH proceeds with high stereospecificity. The configuration at C-20, C-22, C-23, and C-25 for the new iso-type 23-acetyl-spirostanol 15 was established by X-ray crystal analysis as 20 R, 22 R, 23 S, and 25 R. In addition to the above, the X-ray of 15 was analyzed and compared with the crystallographic data of sarsasapogenin acetate (16), smilagenin (4) and 23-acetyl- sarsasapogenin (17).

The synthesis of a Co metal–organic framework assembled from 5,10,15,20-tetrakis((pyridin-4-yl)phenyl)porphyrin; TPhPyP) “Co-MTPhPyP” is reported. The TPhPyP ligand was synthesized via aldehyde condensation in 28% yield and characterized by ¹H nuclear magnetic resonance (¹H NMR), Fourier-transform infrared (FTIR), high-resolution mass spectrometry (HRMS), and UV-visible spectroscopy (UV-vis). Co-MTPhPyP was prepared by the solvothermal method from TPhPyP and CoCl₂·H₂O in 55% yield and characterized by X-ray powder diffraction (XRD), FTIR, thermogravimetric analysis (TGA), field-emission scanning electron microscopy with energy-dispersive X-ray (FESEM-EDS), X-ray photoelectron spectroscopy (XPS), and dynamic light scattering (DLS), showing a particle size distribution of 418 ± 58 nm. The sorption properties of the Co-MTPhPyP for the effective removal of Pb(II) and Cu(II) were evaluated in an aqueous medium and Cthe results showed uptake capacities of 383.4 and 168 mg of the metal g⁻¹ after 2 h, respectively. Kinetic studies of Pb(II) adsorption by Co-MTPhPyP were adjusted to the pseudo-second-order model with a maximum adsorption capacity of 458.8 mg g⁻¹ at 30 min of exposition.

Lanthanide metal–organic frameworks (lanthanide MOFs) may be utilized for a variety of environmental and human health applications due to their luminescent properties and high thermal and water stability. However, the cytotoxic and epigenetic effects produced in human cells are not known. Therefore, we evaluated the cytotoxic effects, internalization, and changes in the mRNA abundance of DNA methylation and demethylation enzymes by exposing human fibroblast cells to a metal–organic framework [H₂NMe₂]₃ [Tb(III)(2,6 pyridinedicarboxylate)₃] (Tb-MOF). For this purpose, the cells were exposed to six concentrations (0.05 to 1.6 mg/mL) of Tb-MOF for 48 h. Field emission electron microscopy coupled to linear energy dispersive spectroscopy (FESEM‒EDS) and confocal microscopy analysis were performed. The cytotoxicity was determined with crystal violet and MTT assays. The results demonstrated the internalization of Tb-MOF at concentrations as low as 0.05 mg/mL, as well as concentration-dependent toxicity. Additionally, we detected significant changes in the gene expression levels of DNA methyltransferases and demethylases due to the presence of Tb-MOF, suggesting that Tb-MOF could generate epigenetic changes even at low concentrations. The results of our study may establish a foundation for future research attempting to develop and apply secure nanomaterials (e.g., MOFs) to minimize damage to the environment and human health.

Metal–organic frameworks (MOFs) are a new class of hybrid porous materials built from organic linkers and inorganic metals, and have been used as adsorbent materials for the removal of heavy metals present in wastewater. While MOFs reduce the toxicity of wastewater by removing heavy metals, it has been reported that they can present some inhibitory effects, intrinsically or through the release of their metal cluster, although these aspects have only rarely been reported. In this work, the toxicity of [Co₂(btec)(bipy)(DMF)₂]_n (MOF-Co), as well as its impact on the toxicity exerted by As(III), was examined using activated sludge in the treatment of synthetic wastewater as an experimental model. Toxicity was assessed through microrespirometry using a wide range of MOF-Co and As(III) concentrations in different configurations. In each case, inhibition was quantified, and the main kinetic parameters were determined. The obtained results confirmed the noncompetitive inhibitory effect of As(III), as well as a significant reduction (by up to 98%) in this inhibitory effect in the presence of MOF-Co. It is concluded that MOF-Co has no effect on activated sludge and might be an efficient material for the removal of heavy metals in wastewater, although further studies are required to establish efficient application and recovery methods.

Phenolic compounds with antioxidant properties are highly sensitive molecules, which limits their application. In response, extruded esterified starch has been proposed as efficient encapsulating material. In this work, we aim to describe the encapsulation of red sorghum phenolic compounds by spray drying using extruded phosphorylated, acetylated and double esterified sorghum starch as wall material. Their respective encapsulation yields were 77.4, 67.4 and 56.8 %, and encapsulation efficiency 91.4, 89.7 and 84.6 %. Degree of substitution confirmed esterification of the sorghum starch and Fourier transform infrared spectroscopy showed the significant chemical and structural changes in the extruded esterified starch loaded with phenolic compounds. Microcapsules from phosphorylated sorghum starch showed the highest endothermic transition (173.89 °C) and provided a greater protection of the phenolic compounds during storage at 60 °C for 35 days than the other wall materials. Extruded esterified sorghum starch proved to be effective material for the protection of phenolic compounds due to its high encapsulation efficiency and stability during storage.