Skin dryness and xerosis are the most common clinical manifestations of different dermatological diseases. The results of research showed that the clinically recommended emolients targeted on skin hydration and recovery of epidermal lipid barrier aren’t sufficient in the treatment of skin atopic diseases and may make skin dryer. Meanwhile, it was established that expression of aquaporines 3 (AQP3) is related to the pathogenesis of atopic dermatitis, psoriasis, eczema, and vitiligo. AQP3 provide a transport of water, glycerol and molecules of natural moisturizing factor increasing the skin hydration, proliferation of keratinocytes and wound healing. Thus, our study was focused on a search of new molecules and investigation theirs biological activity to accelerate expression of AQP3 in skin epidermis. Using DiffDock computational modelling to predict affinity for skin AQP3, aloin and emodin from Aloe vera extract were chosen as new potential candidates. These natural molecules demonstrated a good affinity towards the active site of AQP3 with an estimated docking score from -6.2 kcal/mol to -7.7 kcal/mol. To improve the affinity and stabilize the structure, trimethylglycine was suggested as natural osmolyte. Thorough Phyto4Health modelling to predict the pharmacological properties, it was found that these molecules could have anti-psoriatic, anti-inflammatory, and immunosuppressant activities useful for the treatment of skin atopic diseases. Furthermore, it was shown that combination of Aloe vera extract and trimethylglycine in a mass ratio of 1:1 revealed a clear synergetic effect to increase AQP3 amount up to 2 times, with a ratio and dose-dependent manner. Thus, the combination of Aloe vera extract and trimethylglycine has a promising potential in the drug development and treatment of severe dermatological diseases.

Conjugated ynones, in particular α,β-acetylenic ketones, are of great interest due to their wide range of applications in natural products and in organic synthesis. They are versatile intermediates for the preparation of heterocyclic derivatives such as pyrroles, furans, pyrazoles, isoxazoles and others.

Recently, the catalytic coupling of acyl chlorides and terminal alkynes to give ynones, known as the acyl Sonogashira reaction, has received considerable attention. Typically, this transformation is conducted under conventional conditions for the Sonogashira coupling involving Pd(PPh₃)₂Cl₂, CuI, and TEA. Nevertheless, heterogeneous palladium or copper catalysts have also demonstrated to be efficient in this coupling reaction. In particular, there has been a great interest in using metallic nanoparticles as catalysts due to their high activity and selectivity, and the possibility to recover and reuse the catalyst. In this sense, our research group possesses extensive experience in the preparation of metallic nanocatalysts and their application in various chemical transformations, including cycloaddition reactions, C-C and C-Het. bond forming reactions, reduction and oxidation of different functionalities, among others.

In this work, we want to present our findings on the acyl-Sonogashira coupling catalyzed by copper (monometallic) or copper-palladium (bimetallic, 4:1 molar ratio) nanoparticles (NPs) immobilized in various inorganic materials. We found that the reaction must be conducted at 80°C when using CuNPs, whereas Cu-PdNPs demonstrates exceptional efficiency in promoting the reaction at room temperature. Both catalysts can be reused without any pre-treatment after separation from the reaction medium and subsequent washing.

2,5-diketopiperazines (2,5-DKPs) are the smallest cyclic peptides in nature and display a variety of bioactivities including antibacterial, antifungal, and anticancer, which are well documented pharmacophore. The one-pot synthesis of 2,5-DKPs is few reported. Herein, we report a novel one-pot synthesis of 2,5-DKPs via Ugi-4CR/S_N2-cyclization strategy, under mild conditions, ethanol was used as a solvent for both procedures.

In this work, we present the design and synthesis of the bisthiosemicarbazone ligand H₃L^Me by means of an iminic condensation reaction between 2-hydroxyisophthalaldehyde and 4-methyl-3-thiosemicarbazide. This ligand is bicompartimental, pentadentate [N₂S₂O] and trianionic. The presence of a spacer constituted by a phenol group facilitates the coordination of transition metal ions, giving rise to a great variety of structures. To confirm the purity of the ligand, different characterization techniques were employed, including elemental analysis, mass spectrometry, infrared spectroscopy, and nuclear magnetic resonance. The acquisition of suitable crystals of H₃L^Me allowed us to analyze its structure through X-ray diffraction studies.

Photosensitizers are light-activated compounds that play a crucial role in the field of photodynamic therapy (PDT), an emerging non-invasive therapeutic modality for the treatment of various diseases, including cancer. Photodynamic therapy combines light and photosensitizers in the presence of oxygen to generate cytotoxic reactive oxygen species (ROS) and induce cellular death. In fact, PDT relies on the ability of photosensitizers to be selectively activated by light, allowing for precise spatial over treatment, and minimizing collateral damage to healthy cells and tissues.

Amongst the well-known photosensitizers (e.g. porphyrins, chlorin, xanthene, and ruthenium-based complexes), BODIPY derivatives have shown promising potential because of their highly tunable photophysical properties and versatile synthetic accessibility. Several studies have explored the optimization of the BODIPY core to improve singlet-to-triplet intersystem crossing and efficiency to generate singlet oxygen (singlet oxygen quantum yields). For example, the halogen substitution at the BODIPY core significantly impacts their photophysical properties by enhancing intersystem crossing to the triplet state, suggesting these derivatives may act as effective PDT photosensitizers.

As an extension of the work developed in our research group, we report the design and evaluation of BODIPY derivatives functionalized with an anthracene group at meso and an iodine or formyl group at 2,6-position of the core. The photophysical characterization of the derivatives and the in vitro PDT studies in cancer cells (4T1 cell line) were performed to determine their potential as PDT photosensitizers. The formylated anthracene-BODIPY derivative exhibited the highest tumor suppression under irradiation, making it a potential candidate as PDT photosensitizer.

The imidazo[2,1-b]thiazole scaffold is widely present in natural and synthetic compounds with important properties or biological activities such as anti-inflammatory, antibacterial, antituberculosis, cytotoxic, anthelmintic, antihypertensive or herbicidal. The isocyanide multicomponent reaction (I-MCR) process is a greener alternative efficient synthetic tool. Herein we described a novel methodology to the one pot synthesis of imidazo[2,1-b]thiazole by Groebke-Blackburn-Bienaymé reaction using a few explored 3-formylchromone.

The α7 nicotinic acetylcholine receptor (α7 nAChR), a pentameric ligand-gated ion channel, is widely distributed throughout the central nervous system, particularly in the hippocampus and cortex. Enhancing its function using positive allosteric modulators (PAMs) represents a promising therapeutic approach for treating cognitive deficits and neurodegenerative disorders.

Continuing with our previous work in the search for novel allosteric modulators of α7 nAChR, this study presents the synthesis and biological evaluation of novel isoxazole-vanillin derivatives exhibiting α7-PAM activity.

The one-pot synthesis of 3,5-disubstituted isoxazoles were carried out through the cycloaddition reaction involving in situ generated nitrile oxides from different benzaldehydes and terminal alkynes generated from different benzaldehydes and terminal alkynes, catalyzed by supported copper nanoparticles (CuNPs). For the biological evaluation, single-channel currents were recorded from cells expressing human α7 wild type activated by acetylcholine (ACh). Isoxazole derivatives with functional α7-PAM activity were identified at the single-channel level, measuring currents in the presence of ACh (100 μM) and the synthetic compounds at different concentrations.

Upon evaluating the compounds, we found that only vanillin-derived isoxazoles (containing the 4-hydroxy-3-methoxy fragment) exhibited α7-enhancing activity in comparison to isoxazoles derived from dihydroxy- or dimethoxybenzaldehydes. The use of different substituted phenylacetylenes allowed us to create a small library of compounds with α7-PAM activity.

Catechol derivatives are promising for functional materials due to their metal-chelating ability, making them excellent ligands for generating Coordination Polymer Particles (CPPs). They self-assemble into CPPs from metal ions and polydentate organic ligands, up till now polymeric structure characterization remains challenging. Predicting CPPs properties (morphology, size, stability) in diverse environments is essential for their applications.

In this context, by employing DFT calculations on an iron/catechol-derivatives system, the study aims to investigate the effect on the structure of CPPs materials based on: (a) the utilization of Fe²⁺ and Fe³⁺ in high and low spin states; (b) the type of chelating groups in catechol derivatives and their geometries; and (c) the distance between two chelating groups in a model polydentate ligand.

Geometry optimizations were performed with the BP86 functional. SP Energy calculations with wB97X-D3BJ and the def2 TZVPP(Fe), TZVP(O,N) and SVP(other) basis sets. Iron complexes were modelled with simplified representative ligands: [Fe(catechol_n)]_n=2,3 and [Fe(cat₂)L₂] (L=2-vynilpyridine(pyr), methanethiolate). Fe³⁺ complexes in high-spin had the lowest formation energy. The trans-[Fe(cat)₂(pyr)₂] octahedral complex emerged as the most stable, followed by the tetrahedral [Fe(cat₂)]. 3-((5-mercaptoalkyl)thio)benzene-1,2-diol was employed as the model ligand with a methylene chain (C2-C8) between the chelating groups. The length and conformation of this chain could significantly affect CPPs formation, as it may precipitate as a stable monomer, inhibiting polymer growth. Calculation indicated that monomer formation required a minimum of three methylene units in the chain, with the cis conformation being preferred. Longer chains were favored for the dimers formation, with C4 being most stable.

Lipid droplets (LDs) and lysosomes are important organelles in cellular metabolism and physiology, playing vital roles in maintaining intracellular homeostasis. LDs not only store and metabolize neutral lipids, but also contribute to energy balance, membrane dynamics, and lipid trafficking within cells. Dysfunctional LDs can lead to metabolic disorders and diseases like obesity, fatty liver diseases, diabetes, and certain cancers. Likewise, lysosomes are acidic organelles that significantly contribute to degrading cellular waste and maintaining cellular health. Irregularities in lysosome function can lead to various diseases, including lysosomal storage disorders, neurodegenerative and metabolic diseases, as well as cancer. Therefore, it is crucial to have reliable imaging tools for exploring these cellular structures.

Fluorescent probes represent a useful tool for studying specific structures or molecules within cells with spatiotemporal precision. These probes enable the visualization of cellular morphology, tracking of molecular processes, and studying biomolecules behaviour in real-time. 3-Difluoroborodipyrromethene (BODIPY) derivatives have stood out in this field due to their outstanding optical and physical properties, low phototoxicity and photobleaching, strong absorption, high quantum yield, and ease of synthesis. In this context, we report two BODIPY-based fluorescent probes, functionalized with formyl group or benzimidazole heterocyclic moiety at position 2 of the BODIPY core, designed for live cell imaging of lysosomes and lipid droplets. In vitro experiments using confocal microscopy in HeLa cells demonstrated the probe's ability to permeate the cell membrane and selectively label lysosomes and lipid droplets without causing any adverse effects on the cultured cells. These BODIPYs represent a promising tool for intracellular detection of lysosomes and lipid droplets through fluorescence imaging.

Herein, the synthesis of chiral spirooxindols through different amino catalytic activation modes is described. Several dienophiles were obtained from the Knoevenagel reaction of isatin and activated methylene derivatives containing electron withdrawing groups, such as ethyl cyanoacetate. A spirooxindol derivative was obtained from the oxa-Michael-Michael reaction between one of the synthesized dienophiles and 2-hydroxycinnamaldehyde. Currently, new methodologies that allow access to spirooxindol scaffolds are being explored, mainly though Diels-Alder reactions between 2-methylenindolin-2-ones and aldehydes with trienamine activation mode. The following cascade reactions will be explored in the future to obtain the proposed polycyclic spirooxindol derivatives.