Search Results (114)

Low-density lipoprotein (LDL) chemically modified by reactive oxygen species (ROS), for example, leaking from red blood cells in the vascular compartment, more readily crosses the vascular endothelium than does nonoxidatively modified LDL to enter tissue fluid. Oxidatively modified LDL (oxLDL) may also be created in the tissue fluid by ROS leaking from cells by design, for example, by inflammatory white cells, or simply leaking from other cells as a consequence of oxygen metabolism. As well as oxLDL, glycatively modified LDL (glycLDL) is formed in the circulation. High-density lipoprotein (HDL) appears capable of decreasing the burden of lipid peroxides formed on LDL exposed to ROS or to glucose and its metabolites. The mechanism for this that has received the most attention is the antioxidant activity of HDL, which is due in large part to the presence of paraoxonase 1 (PON1). PON1 is intimately associated with its apolipoprotein A1 component and with HDL’s lipid domains into which lipid peroxides from LDL or cell membranes can be transferred. It is frequently overlooked that for PON1 to hydrolyze lipid substrates, it is essential that it remain by virtue of its hydrophobic amino acid sequences within a lipid micellar environment, for example, during its isolation from serum or genetically modified cells in tissue culture. Otherwise, it may retain its capacity to hydrolyze water-soluble substrates, such as phenyl acetate, whilst failing to hydrolyze more lipid-soluble molecules. OxLDL and probably glycLDL, once they have crossed the arterial endothelium by receptor-mediated transcytosis, are rapidly taken up by monocytes in a process that also involves scavenger receptors, leading to subendothelial foam cell formation. These are the precursors of atheroma, inducing more monocytes to cross the endothelium into the lesion and the proliferation and migration of myocytes present in the arterial wall into the developing lesion, where they transform into foam cells and fibroblasts. The atheroma progresses to have a central extracellular lake of cholesteryl ester following necrosis and apoptosis of foam cells with an overlying fibrous cap whilst continuing to grow concentrically around the arterial wall by a process involving oxLDL and glycLDL. Within the arterial wall, additional oxLDL is generated by ROS secreted by inflammatory cells and leakage from cells generally when couplet oxygen is reduced. PON1 is important for the mechanism by which HDL opposes atherogenesis, which may provide a better avenue of inquiry in the identification of vulnerable individuals and the provision of new therapies than have emerged from the emphasis placed on its role in RCT. Full article

Melanin overproduction causes various skin diseases, such as spots, freckles, and wrinkles, resulting in the requirement of melanin synthesis inhibitors like 1-phenyl-2-thiourea (PTU) and kojic acid, which have been commonly used in the pharmaceutical industry. However, these inhibitors can cause side effects such as skin irritation and allergies. Therefore, it is necessary to develop safe and effective melanin inhibitors from natural resources. The purpose of this study was to investigate a whitening agent from natural substances using B16F10 melanoma cells and zebrafish model. We investigated the melanogenesis-inhibiting activities of the fractions from Sargassum pallidum extract. The ethyl acetate fraction from S. pallidum extract (SPEF) significantly decreased tyrosinase activity. SPEF also significantly reduced α-melanocyte stimulating hormone (MSH)-induced intracellular tyrosinase activity and melanin content in B16F10 cells. Moreover, SPEF inhibited the expression levels of key melanogenic proteins such as tyrosinase, TRP-1, TRP-2, and MITF by downregulating the phosphorylation levels of CREB and PKA in α-MSH-stimulated melanoma cells. Furthermore, SPEF significantly suppressed melanin synthesis in the zebrafish model with no developmental toxicity. LC-Q-TOF-MS/MS analysis identified that SPEF was composed of 12 phytochemical compounds, including diterpenes, which were the dominant metabolites. These results altogether show that SPEF effectively suppresses melanogenesis in B16F10 melanoma cells and in a zebrafish model, with potential for usage in pharmaceuticals and cosmeceuticals. Full article

The serine/threonine kinase CK2 (formerly known as casein kinase II) plays a crucial role in various CNS disorders and is highly expressed in various types of cancer. Therefore, inhibiting this key kinase could be promising for the treatment of these diseases. The CK2 holoenzyme is formed by the recruitment of two catalytically active CK2α and/or CK2α′ subunits by a regulatory CK2β dimer. Starting with the lead furocarbazole W16 (4) inhibiting the CK2α/CK2β interaction, analogous pyrrolocarbazoles were prepared and tested for their protein–protein interaction inhibition (PPII). The key step of the synthesis was a multicomponent Levy reaction of 2-(indolyl)acetate 6, benzaldehydes 7, and N-substituted maleimides 8. Targeted modifications were performed by the saponification of the tetracyclic ester 9a, followed by the coupling of the resulting acid 10 with diverse amines. The replacement of the O-atom of the lead furocarbazole 4 by an N-atom in pyrrolocarbazoles retained or even increased the inhibition of the CK2α/CK2β interaction. The large benzyloxazolidinyl moiety of 4 could be replaced by smaller N-substituents without the loss of the PPII. The introduction of larger substituents at the 2-position and/or at p-position of the phenyl moiety at the 10-position to increase the surface for the inhibition of the PPI did not enhance the inhibition of the CK2α/CK2β association. The strong inhibition of the CK2α/CK2β association by the histidine derivative (+)-20a (K_i = 6.1 µM) translated into a high inhibition of the kinase activity of the CK2 holoenzyme (CK2α₂β₂, IC₅₀ = 2.5 µM). Thus, 20a represents a novel lead compound inhibiting CK2 via the inhibition of the association of the CK2α and Ck2β subunits. Full article

Background/Objectives: The therapeutic management of melanoma, the most aggressive form of skin cancer, remains challenging. In the search for more effective therapeutic options, metal-based complexes are being investigated for their anticancer properties. Cisplatin was the first clinically approved platinum-based drug and, based on its success, other metals (e.g., gold) are being used to design novel compounds. Methods: the antimelanoma potential of a new organometallic cyclometalated Au(III) complex [[Au(C^NOxN)Cl₂] (C^NOxN = 2-(phenyl-(2-pyridinylmethylene)aminoxy acetic acid))] (ST004) was evaluated in vitro and in vivo. Furthermore, the gold-based complex was incorporated in liposomes to overcome solubility and stability problems, to promote accumulation at melanoma sites and to maximize the therapeutic effect while controlling its reactivity. The antiproliferative activity of ST004 formulations was assessed in murine (B16F10) and human (A375 and MNT-1) melanoma cell lines after 24 and 48 h incubation periods. The proof-of-concept of the antimelanoma properties of ST004 formulations was carried out in subcutaneous and metastatic murine melanoma models. Results: the developed liposomal formulations showed a low mean size (around 100 nm), high homogeneity (with a low polydispersity index) and high incorporation efficiency (51 ± 15%). ST004 formulations exhibited antiproliferative activity with EC₅₀ values in the μmolar range being cell-line- and incubation-period-dependent. On the opposite side, the benchmark antimelanoma compound, dacarbazine (DTIC), presented an EC₅₀ > 100 μM. Cell cycle analysis revealed an arrest in G0/G1 phase for Free-ST004 in all cell lines. In turn, LIP-ST004 led to a G0/G1 halt in B16F10, and to an arrest in S phase in A375 and MNT-1 cells. Preliminary mechanistic studies in human red blood cells suggest that gold-based inhibition of glycerol permeation acts through aquaglyceroporin 3 (AQP3). In a metastatic murine melanoma, a significant reduction in lung metastases in animals receiving LIP-ST004, compared to free gold complex and DTIC, was observed. Conclusion: This study highlights the antimelanoma potential of a new gold-based complex. Additional studies, namely in vivo biodistribution profile and therapeutic validation of this organogold complex in other melanoma models, are expected to be performed in further investigations. Full article

An innovative SPME head space GC–MS method, in cooling mode, using a fully automated routine, was developed to detect 2-phenyl-2-propanol, a representative urinary metabolite of cumene. Following an acid hydrolysis and derivatization step with lowered quantities of reagents, acetic anhydride and pyridine, a 30 μm polydimethylsiloxane SPME fiber was used to sample derivatized 2-phenyl-2-propanol, such as benzenemethanol,α,α-dimethyl-acetate, from the headspace. Performances of the method, optimized through experimental design, provide an LOD of 0.034 mg/L and an LOQ 0.10 mg/L, with a short sampling time necessary per sample. The method, developed on standard solutions, will be applied to both occupationally exposed and non-exposed populations. Full article

The title compound, 4-(10-phenyl-9-anthracenyl)-1,2-benzenediol, was synthesized using a two-step protocol. In the first step, 9-phenyl,10-bromoanthracene was coupled to 3,4-dimethoyphenylboronic acid by employing Pd(PPh₃)₄ as the catalyst and potassium carbonate as the base. Methoxy group removal was effected using HBr in the presence of acetic acid in the second step. Overall, two novel 9,10-diphenylanthracence-based compounds were synthesized in this work; standard spectroscopic techniques and high-resolution mass spectrometry were employed in their characterization. The photophysical properties of these compounds are also reported. These compounds are potentially useful as sensors, catalysts and building blocks for larger architectures. Full article

New phenylacetic acid derivatives with potentially valuable biological activities and the ability to act as starting materials for various functionalizations have been prepared by a multi-step synthesis. Starting from 2,6-dibromo-4-methylaniline, the synthetic route involves the construction of the basic aromatic structure (3,4,5-triphenyltoluene) (two steps), followed by its conversion into 2-[(3,4,5-triphenyl)phenyl]acetic acid and derivatives (up to five steps). Based on this multi-step synthesis, five compounds not previously reported in the literature were synthesized; the literature-known 3,4,5-triphenyltoluene was synthesized for the first time in the manner described. This synthesis is applicable for the preparation of numerous new representatives of this class of compounds. Full article

Drug candidates must undergo thermal evaluation as early as possible in the preclinical phase of drug development because undesirable changes in their structure and physicochemical properties may result in decreased pharmacological activity or enhanced toxicity. Hence, the detailed evaluation of nitrogen-rich heterocyclic esters as potential drug candidates, i.e., imidazolidinoannelated triazinylformic acid ethyl esters 1–3 (where R₁ = 4–CH₃ or 4–OCH₃ or 4–Cl, and R₂ = –COOC₂H₅) and imidazolidinoannelated triazinylacetic acid methyl esters 4–6 (where R₁ = 4–CH₃ or 4–OCH₃ or 4–Cl, and R₂ = –CH₂COOCH₃)—in terms of their melting points, melting enthalpy values, thermal stabilities, pyrolysis, and oxidative decomposition course—has been carried out, using the simultaneous thermal analysis methods (TG/DTG/DSC) coupled with spectroscopic techniques (FTIR and QMS). It was found that the melting process (documented as one sharp peak related to the solid–liquid phase transition) of the investigated esters proceeded without their thermal decomposition. It was confirmed that the melting points of the tested compounds increased in relation to R₁ and R₂ as follows: 2 (R₁ = 4–OCH₃; R₂ = –COOC₂H₅) < 6 (R₁ = 4–Cl; R₂ = –CH₂COOCH₃) < 5 (R₁ = 4–OCH₃; R₂ = –CH₂COOCH₃) < 3 (R₁ = 4–Cl; R₂ = –COOC₂H₅) < 1 (R₁ = 4–CH₃; R₂ = –COOC₂H₅) < 4 (R₁ = 4–CH₃; R₂ = –CH₂COOCH₃). All polynitrogenated heterocyclic esters proved to be thermally stable up to 250 °C in inert and oxidising conditions, although 1–3 were characterised by higher thermal stability compared to 4–6. The results confirmed that both the pyrolysis and the oxidative decomposition of heterocyclic ethyl formates/methyl acetates with para-substitutions at the phenyl moiety proceed according to the radical mechanism. In inert conditions, the pyrolysis process of the studied molecules occurred with the homolytic breaking of the C–C, C–N, and C–O bonds. This led to the emission of alcohol (ethanol in the case of 1–3 or methanol in the case of 4–6), NH₃, HCN, HNCO, aldehydes, CO₂, CH₄, HCl, aromatics, and H₂O. In turn, in the presence of air, cleavage of the C–C, C–N, and C–O bonds connected with some oxidation and combustion processes took place. This led to the emission of the corresponding alcohol depending on the analysed class of heterocyclic esters, NH₃, HCN, HNCO, aldehydes, N₂, NO/NO₂, CO, CO₂, HCl, aromatics, and H₂O. Additionally, after some biological tests, it was proven that all nitrogen-rich heterocyclic esters—as potential drug candidates—are safe for erythrocytes, and some of them are able to protect red blood cells from oxidative stress-induced damage. Full article

The carboxylation of unsaturated amine and alcohol compounds, including 4-benzylamino-1-phenyl-1-butyne (homopropargylamine), 2-butyne-1-ol (propargylic alcohol), and 2,3-butadiene-1-ol (allenylmethyl alcohol), using the hydroxidogold(I) complex, AuOH(IPr) [IPr = 1,3-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene], produces corresponding alkenylgold(I) complexes with a cyclic urethane or carbonate framework in high yields. The reaction takes place in aprotic THF at room temperature under the atmospheric pressure of CO₂ in the absence of base additives. The products were characterized by NMR spectroscopy, elemental analysis, and X-ray crystallography. The functionalized alkenyl complexes prepared from the alkynes can be protonated by treatment with an equimolar amount of acetic acid to afford five- or six-membered carboxylation products, whereas the related alkenyl complex derived from allenylmethyl alcohol decomposed to recover the starting allene via ring-opening decarboxylation. Full article

We tested five chemically and metabolically stable prostaglandin (PG) receptor agonists in a mouse model of dexamethasone-induced ocular hypertension (OHT). Whilst all compounds significantly (p < 0.05, ANOVA) lowered intraocular pressure (IOP) after twice-daily bilateral topical ocular dosing (5 µg/dose) over three weeks, the time course and magnitude of the responses varied. The onset of action of NS-304 (IP-PG receptor agonist) and rivenprost (EP4-PG receptor agonist) was slower than that of misoprostol (mixed EP2/EP3/EP4-PG receptor agonist), PF-04217329 (EP2-PG receptor agonist), and butaprost (EP2-PG receptor agonist). The rank order of IOP-lowering efficacies aligned with the onset of actions of these compounds. Peak IOP reductions relative to vehicle controls were as follows: misoprostol (74.52%) = PF-04217329 (74.32%) > butaprost (65.2%) > rivenprost (58.4%) > NS-304 (55.3%). A literature survey indicated that few previously evaluated compounds (e.g., latanoprost, timolol, pilocarpine, brimonidine, dorzolamide, cromakalim analog (CKLP1), losartan, tissue plasminogen activator, trans-resveratrol, sodium 4-phenyl acetic acid, etc.) in various animal models of steroid-induced OHT were able to match the effectiveness of misoprostol, PF-04217329 or butaprost. Since a common feature of the latter compounds is their relatively high affinity and potency at the EP2-PG receptor sub-type, which activates the production of intracellular cAMP in target cells, our studies suggest that drugs selective for the EP2-PG receptor may be suited to treat corticosteroid-induced OHT. Full article

In this study, two strains of Schizosaccharomyces pombe (NCAIM Y01474^T and SBPS) and two strains of Schizosaccharomyces japonicus (DBVPG 6274^T, M23B) were investigated for their capacity to ferment apple juice and influence the volatile compounds of cider compared to Saccharomyces cerevisiae EC1118. The ethanol tolerance and deacidification capacity of Schizosaccharomyces yeasts could make them potential substitutes for the commonly used S. cerevisiae starter cultures. Despite different time courses (10–30 d), all strains could complete the fermentation process, and Schizosaccharomyces strains reduced the concentration of malic acid in the apple juice. Results indicated that each yeast exerted a distinctive impact on the volatile profile of the apple cider, giving final products separated using a principal component analysis. The volatile composition of the cider exhibited significant differences in the concentration of alcohols, esters, and fatty acids. Particularly, the flocculant strain S. japonicus M23B increased the levels of ethyl acetate (315.44 ± 73.07 mg/L), isoamyl acetate (5.99 ± 0.13 mg/L), and isoamyl alcohol (24.77 ± 15.19 mg/L), while DBVPG 6274^T incremented the levels of phenyl ethyl alcohol and methionol up to 6.19 ± 0.51 mg/L and 3.72 ± 0.71 mg/L, respectively. A large production of terpenes and ethyl esters (e.g., ethyl octanoate) was detected in the cider fermented by S. cerevisiae EC1118. This study demonstrates, for the first time, the possible application of S. japonicus in cider-making to provide products with distinctive aromatic notes”. Full article

Non-alcoholic beer (NAB) and low-alcoholic beer (LAB) are taking over the market with growing sales. Sustainable recycling and valorization of exhausted brewer’s spent grain (BSG) coming from craft beer is a relevant issue in the brewing process. In this work, recycled BSG and BSG + GJ (supplemented with 10% grape juice) were used as a wort substrate to inoculate Lachancea thermotolerans, Wickeramhomyces anomalus, Torulaspora delbruecki and Pichia kluyveri non-conventional yeasts to produce NABLAB craft beer. Results showed that wort composed of only recycled BSG produced appreciated NAB beers (ethanol concentration from 0.12% to 0.54% v/v), while the addition of 10% grape juice produced LAB beers (ethanol concentration from 0.82 to 1.66% v/v). As expected, volatile compound production was highest with the addition of grape juice. L. thermotolerans showed lactic acid production, characterizing both worts with the production of ethyl butyrate and isoamyl acetate. T. delbrueckii exhibited relevant amounts of hexanol, phenyl ethyl acetate and β-phenyl ethanol (BSG + GJ). W. anomalus and P. kluyveri showed consistent volatile production, but only in BSG + GJ where fermentation activity was exhibited. The overall results indicated that reused BSGs, non-conventional yeasts and grape juice are suitable bioprocesses for specialty NABLAB beer. Full article

Bidens pilosa L. is native to tropical America and has widely naturized from tropical to warm temperate regions in Europe, Africa, Asia, Australia, and North and South America. The species has infested a wide range of habitats such as grasslands, forests, wetlands, streamlines, coastal areas, pasture, plantations, agricultural fields, roadsides, and railway sides and has become a noxious invasive weed species. B. pilosa forms thick monospecific stands, quickly expands, and threatens the indigenous plant species and crop production. It is also involved in pathogen transmission as a vector. The species was reported to have (1) a high growth ability, producing several generations in a year; (2) a high achene production rate; (3) different biotypes of cypselae, differently germinating given the time and condition; (4) a high adaptative ability to various environmental conditions; (5) an ability to alter the microbial community, including mutualism with arbuscular mycorrhizal fungi; and (6) defense functions against natural enemies and allelopathy. The species produces several potential allelochemicals such as palmitic acid, p-coumaric acid, caffeic acid, ferulic acid, p-hydroxybenzoic acid, vanillic acid, salycilic acid, quercetin, α-pinene, and limonene and compounds involved in the defense functions such as 1-phenylhepta-1,3,5-trine, 5-phenyl-2-(1-propynyl)-thiophene, 5-actoxy-2-phenylethinyl-thiophene, and icthyothereol acetate. These characteristics of B. pilosa may contribute to the naturalization and invasiveness of the species in the introduced ranges. This is the first review article focusing on the invasive mechanisms of the species. Full article

The chromatographic conditions were optimized using headspace gas chromatography, and a simple and rapid method was established for the simultaneous determination of five residual solvents in ursodeoxycholic acid raw materials. The corresponding quality standards were revised. The research results demonstrate that by utilizing a capillary column with a stationary phase consisting of 5% phenyl-95% dimethylpolysiloxane (HP-5, 30 m × 0.32 mm, film thickness 1.0 µm) and a flame ionization detector in conjunction with a headspace injection system and a programmed temperature ramping method, satisfactory analytical results can be achieved. The specific operating conditions are as follows: an initial column temperature of 45 °C, followed by a column temperature increase at a rate of 5 °C per minute up to 60 °C, then a further increase at a rate of 10 °C per minute up to 100 °C, and finally a rapid increase at a rate of 40 °C per minute up to 200 °C, where it is held for 10 min. Nitrogen is employed as the carrier gas at a flow rate of 1 mL/min with a split ratio of 14:1. The headspace vial temperature is maintained at 100 °C, with a sample equilibration time of 45 min. The concentration of methanol ranged from 0.06 mg/mL to 0.3 mg/mL, and the concentrations of acetone, tert-butanol, ethyl acetate, and triethylamine showed a good linear relationship with the peak area within the range of 0.1 mg/mL to 0.5 mg/mL (r = 0.999); The quantitation limits for methanol, acetone, tert-butanol, ethyl acetate, and triethylamine were 4.2, 0.9, 1.5, 1, and 0.1 μg/mL, respectively, with detection limits of 1.2, 0.25, 0.025, 0.3, and 0.025 μg/mL, respectively. The recovery rates of each solvent ranged from 92.9% to 106.0%, with RSD% (n = 9) less than 3.8%; the method exhibited good repeatability, with RSD% (n = 6) less than 2.5%. Furthermore, the robustness is good. The established method is simple, accurate, specific, and highly sensitive, and can be used for the simultaneous and rapid determination of five residual solvents in ursodeoxycholic acid raw materials. Full article

Bacillus species produce different classes of antimicrobial and antioxidant substances: peptides or proteins with different structural compositions and molecular masses and a broad range of volatile organic compounds (VOCs), some of which may serve as biomarkers for microorganism identification. The aim of this study is the identification of biologically active compounds synthesized by five Bacillus species using gas chromatography coupled to mass spectrometry (GC–MS). The current study profoundly enhances the knowledge of antibacterial and antioxidant metabolites ensuring the unambiguous identification of VOCs produced by some Bacillus species, which were isolated from vegetable samples of potato, carrot, and tomato. Phylogenetic and biochemical studies were used to identify the bacterial isolates after culturing. Phylogenetic analysis proved that five bacterial isolates BSS12, BSS13, BSS16, BSS21, and BSS25 showed 99% nucleotide sequence similarities with Bacillus safensis AS-08, Bacillus cereus WAB2133, Bacillus acidiproducens NiuFun, Bacillus toyonesis FORT 102, and Bacillus thuringiensis F3, respectively. The crude extract was prepared from bacterial isolates to assess the antibiotic resistance potency and the antimicrobial potential against various targeted multidrug-resistant strains, including yeast strains such as Candida albicans, Candida krusei, and bacterial strains of Enterococcus hirae, Escherichia coli, Klebsiella aerogenes, Klebsiella pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus group B, Streptococcus mutans, Shigella sonnei, Salmonella enteritidis, Serratia marcescens, Pseudomonas aeruginosa, and Proteus vulgaris. GC–MS analysis of bacterial strains found that VOCs from Bacillus species come in a variety of chemical forms, such as ketones, alcohols, terpenoids, alkenes, etc. Overall, 69 volatile organic compounds were identified from five Bacillus species, and all five were found to share different chemical classes of volatile organic components, which have a variety of pharmacological applications. However, eight antibacterial compounds with different concentrations were commonly found in all five species: acetoin, acetic acid, butanoic acid, 2-methyl-, oxime-, methoxy-phenyl, phenol, 1,2-benzenedicarboxylic acid, bis(2-methylpropyl) ester, nonanoic acid, and hexadecanoic acid, methyl. The present study has demonstrated that bacterial isolates BSS25, BSS21, and BSS16 display potent inhibitory effects against Candida albicans, while BSS25, BSS21, and BSS13 exhibit the ability to restrain the growth and activity of Candida krusei. Notably, BSS25 and BSS21 are the only isolates that demonstrate substantial inhibitory activity against Klebsiella aerogenes. This disparity in inhibitory effects could be attributed to the higher concentrations of acetoin in BSS25 and BSS21, whereas BSS16 and BSS13 have relatively elevated levels of butanoic acid, 2-methyl-. Certainly, the presence of acetoin and butanoic acid, 2-methyl-, contributes to the enhanced antibacterial potential of these bacterial strains, in conjunction with other organic volatile compounds and peptides, among other factors. The biology and physiology of Bacillus can be better understood using these results, which can also be used to create novel biotechnological procedures and applications. Moreover, because of its exceptional ability to synthesize and produce a variety of different antibacterial compounds, Bacillus species can serve as natural and universal carriers for antibiotic compounds in the form of probiotic cultures and strains to fight different pathogens, including mycobacteria. Full article