Search Results (75)

The title compound, i.e., (Z)-4-(azulen-1-ylmethylene)-2-phenyloxazol-5(4H)-one (3), has previously been synthesized in a good yield (56%) using the Erlenmeyer–Plöchl procedure. The crystal structure of 3 is described herein along with the results of a Hirshfeld surface analysis. Crystals of compound 3 were obtained through the slow evaporation of a mixture of petroleum ether/dichloromethane = 1:1 (vol.) at room temperature. This compound has a monoclinic system: a P2₁/n space group at room temperature. Its crystal packing is driven by π-π interactions between neighboring molecules in the range of 3.60–3.71 Å and by hydrogen bonds (D-H···A = 2.58 Å). Full article

Atopic dermatitis (AD) remains a challenging condition, necessitating effective models for investigation and therapeutic exploration. In this study, we employed a goat skin model to assess the immune response triggered by topical oxazolone (OX) application. The OX simulates a Th2-driven immune reaction typified by elevated Th2 cytokine (IL-4 and IL-13) expression and the infiltration of mononuclear cells magnified by the presence of CD3⁺ and CD4⁺ T-cells in the epidermal and dermal layers. Additionally, the application of pomegranate peel extract (PPE) demonstrated a mitigating effect on OX-induced skin alterations, suggesting potential therapeutic benefits. This study underscores the value of goats as a reliable and accessible model for studying AD in humans and/or large animals. While the therapeutic potential of PPE dosage requires further exploration. Full article

This work aims to amplify the fluorescence of (Z)-4-hetarylidene-5(4H)-oxazolones 1 by suppression of the hula-twist non-radiative deactivation pathway by C^N-orthopalladation of the 4-hetarylidene ring. Different (Z)-4-hetarylidene-2-phenyl-5(4H)-oxazolones, 1a–1c, prepared by the Erlenmeyer–Plöchl method, have been studied. The orthopalladation of (Z)-2-phenyl-4-(5-thiazolylmethylene)-5(4H)-oxazolone (1a) takes place by C-H bond activation of the H4 of the heterocycle and C^N-chelation, giving the dinuclear trifluoroacetate derivative 2a. By further metathesis of bridging ligands in 2a, complexes containing the orthometalated oxazolone and a variety of ligands 3a–5a, were prepared. The study of the photophysical properties of 1a–5a shows that the bonding of the Pd metal to the 4-hetaryliden-5(4H)-oxazolone does not promote, in these cases, an increase in fluorescence. Interestingly, the orthopalladation of (Z)-2-phenyl-4-(4-thiazolylmethylene)-5(4H)-oxazolone (1b) gives orthopalladated 2b, where the incorporation of the Pd to the oxazolone takes place by C-H bond activation of the ortho-H2 of the 2-phenyl group, ring opening of the oxazolone heterocycle and simultaneous N,N-bonding of the N atoms of the thiazole ring and the generated benzamide fragment. This N^N^C-tridentate dianionic bonding mode is obtained for the first time in oxazolones. Despite a similar lock of the hula-twist deactivation, 2b does not show fluorescence. Full article

The skin epidermis provides a barrier that is imperative for preventing transepidermal water loss (TEWL) and protecting against environmental stimuli. The underlying molecular mechanisms for regulating barrier functions and sustaining its integrity remain unclear. RORα is a nuclear receptor highly expressed in the epidermis of normal skin. Clinical studies showed that the epidermal RORα expression is significantly reduced in the lesions of multiple inflammatory skin diseases. In this study, we investigate the central roles of RORα in stabilizing skin barrier function using mice with an epidermis-specific Rora gene deletion (Rora^EKO). While lacking spontaneous skin lesions or dermatitis, Rora^EKO mice exhibited an elevated TEWL rate and skin characteristics of barrier dysfunction. Immunostaining and Western blot analysis revealed low levels of cornified envelope proteins in the Rora^EKO epidermis, suggesting disturbed late epidermal differentiation. In addition, an RNA-seq analysis showed the altered expression of genes related to “keratinization” and “lipid metabolism” in RORα deficient epidermis. A lipidomic analysis further uncovered an aberrant ceramide composition in the Rora^EKO epidermis. Importantly, epidermal Rora ablation greatly exaggerated percutaneous allergic inflammatory responses to oxazolone in an allergic contact dermatitis (ACD) mouse model. Our results substantiate the essence of epidermal RORα in maintaining late keratinocyte differentiation and normal barrier function while suppressing cutaneous inflammation. Full article

The anti-inflammatory, antiviral, and anti-cancer properties, as well as the mechanism of action of cyclo-[Pro-Pro-β³-HoPhe-Phe-] tetrapeptide (denoted as 4B8M), were recently described. The aim of this work was to synthesize and evaluate the immunosuppressive actions of the stereochemical variants of 4B8M by sequential substitution of L-amino acids by D-amino acids (a series of peptides denoted as P01–P07) using parent 4B8M as a reference compound. In addition, diverse available bioinformatics tools using machine learning and artificial intelligence were tested to find the bio-pharmacokinetic and polypharmacological attributes of analyzed stereomers. All peptides were non-toxic to human peripheral blood mononuclear cells (PBMCs) and only cyclo-[D-Pro-Pro-β³-HoPhe-Phe-] peptide (P03) was capable of inhibiting mitogen-induced PBMC proliferation. The peptides inhibited the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) to various degrees, with P04 (cyclo-[Pro-Pro-D-β³-HoPhe-Phe-]) and P03 being the most potent. For further in vivo studies, P03 was selected because it had the combined properties of inhibiting cell proliferation and TNF-α production. P03 demonstrated a comparable ability to 4B8M in the inhibition of auricle edema and lymph node cell number and in the normalization of a distorted blood cell composition in contact sensitivity to the oxazolone mouse model. In the mouse model of carrageenan-induced inflammation of the air pouch, P03 exhibited a similar inhibition of the cell number in the air pouches as 4B8M, but its inhibitory effects on the percentage of neutrophils and eosinophils in the air pouches and blood, as well as on mastocyte degranulation in the air pouches, were stronger in comparison to 4B8M. Lastly, in a mouse model of dextran sulfate-induced colitis, similar effects to 4B8M regarding thymocyte number restoration and normalization of the blood cell pictures by P03 were observed. In summary, depending on either experimental findings or in silico predictions, P03 demonstrated comparable, or even better, anti-inflammatory and bio-pharmacokinetic properties to 4B8M and may be considered as a potential therapeutic. The possibility of P00 and P03 identification by circular dichroism measurements was tested by quantum-chemical calculations. Full article

Yolkin, an egg yolk immunoregulatory protein, stimulates the humoral but inhibits the cellular immune response in adult mice. The aim of this investigation was to evaluate the effects of yolkin administration on the immune response using a model of juvenile, i.e., 28-day- and 37-day-old, mice. We examined the yolkin influence on the magnitude of the cellular immune response, which was determined as contact sensitivity (CS) to oxazolone (OXA), and the humoral immune response, which was determined as the antibody response to ovalbumin (OVA). Yolkin was administered in drinking water, followed by immunization with OXA or OVA. In parallel, the phenotypic changes in the lymphoid organs were determined following yolkin treatment and prior immunization. The results showed that yolkin had a stimulatory effect on CS in the mice treated with yolkin from the 37th day of life but not from the 28th day of life. In contrast, no regulatory effect of yolkin on antibody production was found in 28-day- and 37-day-old mice. Phenotypic studies revealed significant changes in the content of B cells and T cell subpopulations, including CD4+CD25+Foxp3 regulatory T cells. The association between the effects of yolkin on the magnitude of CS and phenotypic changes in main T- and B-cell compartments, as well the importance of changes in T-regulatory and CD8+ cells in the age categories, are discussed. We conclude that the immunoregulatory effects of yolkin on the generation of CS in mice are age dependent and change from stimulation in juvenile to suppression in adult mice. Full article

The genome—the source of life and platform of evolution—is continuously exposed to harmful factors, both extra- and intra-cellular. Their activity causes different types of DNA damage, with approximately 80 different types of lesions having been identified so far. In this paper, the influence of a clustered DNA damage site containing imidazolone (Iz) or oxazolone (Oz) and 7,8-dihydro-8-oxo-2′-deoxyguanosine (^OXOdG) on the charge transfer through the double helix as well as their electronic properties were investigated. To this end, the structures of oligo-Iz, d[A₁Iz₂A₃^OXOG₄A₅]*d[T₅C₄T₃C₂T₁], and oligo-Oz, d[A₁Oz₂A₃^OXOG₄A₅]*d[T₅C₄T₃C₂T₁], were optimized at the M06-2X/6-D95**//M06-2X/sto-3G level of theory in the aqueous phase using the ONIOM methodology; all the discussed energies were obtained at the M06-2X/6-31++G** level of theory. The non-equilibrated and equilibrated solvent–solute interactions were taken into consideration. The following results were found: (A) In all the discussed cases, ^OXOdG showed a higher predisposition to radical cation formation, and B) the excess electron migration toward Iz and Oz was preferred. However, in the case of oligo-Oz, the electron transfer from Oz₂ to complementary C₄ was noted during vertical to adiabatic anion relaxation, while for oligo-Iz, it was settled exclusively on the Iz₂ moiety. The above was reflected in the charge transfer rate constant, vertical/adiabatic ionization potential, and electron affinity energy values, as well as the charge and spin distribution. It can be postulated that imidazolone moiety formation within the CDL ds-oligo structure and its conversion to oxazolone can significantly influence the charge migration process, depending on the C2 carbon hybridization sp² or sp³. The above can confuse the single DNA damage recognition and removal processes, cause an increase in mutagenesis, and harm the effectiveness of anticancer therapy. Full article

A novel aromatic imine derivative, 2′-(1,4-phenylene)bis[4-[(4-methoxyphenyl)methylene]-5(4H)-oxazolone] (PBMBO), was designed and synthesized as a yellow colorant additive for green color filters used in image sensors. The optical and thermal properties of the newly developed material were evaluated both in solution and within color filter film conditions. PBMBO demonstrated a molar extinction coefficient of 2.24 × 10⁴ L/mol·cm in solution, surpassing that of the commercially employed yellow colorant MBIQO by a factor of 1.82. Color resist (CR) films incorporating PBMBO exhibited outstanding optical characteristics, displaying 0.03% transmittance at 435 nm, 99.3% transmittance at 530 nm, and a sharp slope within the 400 to 550 nm range. The decomposition temperature of PBMBO was 303 °C, indicating relatively superior thermal stability compared to MBIQO. Consequently, PBMBO emerges as a highly promising candidate for a yellow colorant additive in imaging sensor color filters, owing to its exceptional optical and thermal stability. Its potential applications are anticipated to extend across various fields of organic semiconductors. Full article

This study aimed to examine the potential impact of the intervention of Lactiplantibacillus plantatum HFY11 (LP-HFY11) on colitis using in vivo animal trials. The impact of LP-HFY11 intervention on colitis was determined by measuring the levels of relevant indicators in the intestine, colon, and blood after oxazolone-induced colitis in BALB/c mice. The results of the trial show that LP-HFY11 improved the colon weight-to-length ratio, reduced the colitis-induced colon length shortening, and reduced colonic abstinence. Furthermore, it decreased the levels of myeloperoxidase, nitric oxide, and malondialdehyde activities while increasing the glutathione content in the colon tissue of colitis-affected animals. LP-HFY11 lowered the interleukin-10 (IL-10) level and increased the IL-2 level in the serum of colitis mice. LP-HFY11 also upregulated the expression of neuronal nitric oxide synthase, endothelial nitric oxide synthase, c-Kit, and stem cell factor (SCF), and downregulated the expression of IL-8, C-X-C chemokine receptor type 2 (CXCR2), and inducible nitric oxide synthase (iNOS) in the colon tissue of mice with colitis. LP-HFY11 decreased the expression of Firmicutes in the gut while increasing the expression of Bacteroidetes, Bifidobacteria, and Lactobacillus. This indicates that LP-HFY11 could control physiological alterations in the serum and colon tissue, as well as the expression of gut microorganism. Full article

[(Z)-2′-{2-C₆H₅-(4H)-oxazol-5-one}CHC₆H₄]₂Se (5, L¹) and [(Z)-4′-{2-C₆H₅-(4H)-oxazol-5-one}CHC₆H₄]₂Se (6, L²) were prepared, structurally characterized and used as ligands to obtain new metal complexes of types [MX(Lⁿ)] [L¹: M = Ag, X = OTf (7); M = Au, X = Cl (13); L²: M = Ag, X = OTf (8); M = Au, X = Cl (14)], [(MX)₂(Lⁿ)] [M = Ag, X = OTf, L¹ (9); L² (10)], [ZnCl₂(Lⁿ)] [L¹ (15); L² (16)] and [Ag(Lⁿ)][PF₆] [L¹ (11); L² (12)]. The silver complexes 7 and 8 were ionic species (1:1 electrolytes) in a MeCN solution, while in the solid state, the triflate fragments were bonded to the silver cations. Similarly, the 2:1 complexes 9 and 10 were found to behave as 1:2 electrolytes in a MeCN solution, but single-crystal X-ray diffraction demonstrated that compound 9 showed the formation of a dimer in the solid state: a tetranuclear [Ag(OTf)]₄ built through bridging triflate ligands was coordinated by two bridging organoselenium ligands through the nitrogen from the oxazolone ring and the selenium atoms in a 1κN:2κSe fashion. Supramolecular architectures supported by intermolecular C−H∙∙∙π, C−H∙∙∙O, Cl∙∙∙H and F∙∙∙H interactions were observed in compounds 4, 5 and 9. The compounds exhibited similar photophysical properties, with a bathochromic shift in the UV-Vis spectra caused by the position of the oxazolone ring on the phenyl ring attached to the selenium atoms. Full article

The protective roles of extracellular vesicles derived from human umbilical cord mesenchymal stem cells against oxazolone-induced damage in the immortalized human keratinocyte cell line HaCaT were investigated. The cells were pretreated with or without UCMSC-derived extracellular vesicles 24 h before oxazolone exposure. The pretreated UVMSC-EVs showed protective activity, elevating cell viability, reducing intracellular ROS, and reducing the changes in the mitochondrial membrane potential compared to the cells with a direct oxazolone treatment alone. The UCMSC-EVs exhibited anti-inflammatory activity via reducing the inflammatory cytokines IL-1β and TNF-α. A mechanism study showed that the UCMSC-EVs increased the protein expression levels of SIRT1 and P53 and reduced P65 protein expression. It was concluded that UVMSC-EVs can induce the antioxidant defense systems of HaCaT cells and that they may have potential as functional ingredients in anti-aging cosmetics for skin care. Full article

Finding an effective anticancer drug to combat cancer cell resistance remains a challenge. Herein, we synthesized a new series of imidazolone derivatives 4a–4i and assessed their anticancer activities against liver cancer cells (Hep3B), Hela cells, and normal LX2 cells. The imidazolne derivatives were synthesized by the condensation cyclization reaction using the natural product vanillin as a starting material. Among the synthesized imidazolones are those with an alkyl sulfate moiety that are water-soluble and showed enhanced anticancer activity against the tested cancer cells. The anticancer testing results showed that compound 4d with the NO₂ group at position 4 of the benzene ring was superior to the other compounds; it showed an IC₅₀ value of 134.2 ± 4.4 µM against Hep3B cells, while compound 4h with the pyridyl moiety showed the highest cytotoxicity against Hela cells with an IC₅₀ of 85.1 ± 2.1 µM. The anticancer activity of some imidazolones was greatly enhanced by adding to them the zwitterionic properties that made them more polar and water-soluble. DNA binding studies with compounds 4a₁, 4d, and 4g indicated a docking score ranging from approximately −6.8 to −8.7 kcal/mol. This could be attributed to the outstanding interaction between the molecule and the DNA binding sites, which primarily relies on its inherent capability to establish hydrogen bonds, facilitated by the electron pair present at the oxygen atoms and the drug’s amino group. In conclusion, water-soluble imidazolone with zwitterionic functionality could be a promising tool for the development of anticancer medication. To outline the general idea and the relationships for the effect of the developed compounds under study, as well as their mechanism of action, further extensive research is also necessary. Full article

We synthesized seven (Z)-benzylidene-2-(E)-styryloxazol-5(4H)-ones derivatives of cinnamic acid and evaluated the ability of these compounds to inhibit human acetylcholinesterase (hAChE). The most potent compound was evaluated for cognitive improvement in short-term memory. The seven compounds reversibly inhibited the hAChE between 51 and 75% at 300 μM, showed an affinity (K_i) from 2 to 198 μM, and an IC₅₀ from 9 to 246 μM. Molecular docking studies revealed that all binding moieties are involved in the non-covalent interactions with hAChE for all compounds. In addition, in silico pharmacokinetic analysis was carried out to predict the compounds’ blood–brain barrier (BBB) permeability. The most potent inhibitor of hAChE significantly improved cognitive impairment in a modified Y-maze test (5 μmol/kg) and an Object Recognition Test (10 μmol/kg). Our results can help the rational design of hAChE inhibitors to work as potential candidates for treating cognitive disorders. Full article

The 3,4-dihydrocoumarin derivatives were obtained from 2-alkyl phenols and oxazolones via C–H oxidation and cyclization cascade in the presence of silver oxide (Ag₂O) and p-toluenesulfonic acid as a Brønsted acid catalyst. This approach provides a one-pot strategy to synthesize the multisubstituted 3,4-dihydrocoumarins with moderate to high yields (64–81%) and excellent diastereoselectivity (>20:1). Full article

The eyes provide themselves with immune tolerance. Frequent skin inflammatory diseases in young blind people suggest, nonetheless, that the eyes instruct a systemic immune tolerance that benefits the whole body. We tested this premise by using delayed skin contact hypersensitivity (DSCH) as a tool to compare the inflammatory response developed by sighted (S) and birth-enucleated (BE) mice against oxazolone or dinitrofluorobenzene at the ages of 10, 30 and 60 days of life. Adult mice enucleated (AE) at 60 days of age were also assessed when they reached 120 days of life. BE mice displayed exacerbated DSCH at 60 but not at 10 or 30 days of age. AE mice, in contrast, show no exacerbated DSCH. Skin inflammation in 60-day-old BE mice was hapten exclusive and supported by distinct CD8⁺ lymphocytes. The number of intraepidermal T lymphocytes and migrating Langerhans cells was, however, similar between S and BE mice by the age of 60 days. Our observations support the idea that the eyes instruct systemic immune tolerance that benefits organs outside the eyes from an early age. The higher prevalence of inflammatory skin disorders reported in young people might then reflect reduced immune tolerance associated with the impaired functional morphology of the eyes. Full article