Search Results (8)

Ergothioneine is a potent non-toxic and very stable antioxidant which is synthesized by fungi, algae, and bacteria but not animals or higher plants. Ergothioneine has been widely used in cosmetics; dietary supplements; and medicine to treat diabetes, cancer, as well as cardiovascular, neurodegenerative, and liver diseases. Ergothioneine presents two tautomeric forms: thione, the majoritarian and more stable form (ERGO), and thiol (ERGT). Ergothioneine cannot cross cell membranes, and human cells rely on a specific transporter, OCTN1, to transport ingested ERGO to different parts of the body. Ergothioneine is very hydrophilic, and it is supposed to act at the water level but not at the membrane one. In this work, I studied the interaction of ERGO and ERGT with a complex biomembrane using molecular dynamics (MD). MD suggests that ERGO, but not ERGT, inserts spontaneously into the membrane interphase and can move from the membrane interphase to the water phase and vice versa, and no oligomerization was observed. Furthermore, ERGO, when inserted in the membrane, does not alter the hydrocarbon chain order. Therefore, ERGO (the thione form of ergothioneine), but not ERGT (the thiol form), might act at both the water and membrane interphase levels. Full article

Surface-enhanced Raman scattering (SERS) spectroscopy is a straightforward analytical technique capable of providing detailed information about metabolites in biological samples. The objective of this study was to perform a SERS analysis of ergothioneine (EGT), an amino acid synthesized by microbes and fungi, across a range of pH values (acidic to alkaline) and concentrations (2 × 10⁻⁵ M to 2 × 10⁻⁷ M), to understand the dynamic interactions between EGT and silver (Ag) nanoparticles. Furthermore, SERS was applied in situ on mushroom fruiting bodies to detect the presence of EGT. The SERS spectra revealed that the interaction of EGT with Ag nanoparticles underwent significant alterations at varying pH levels, primarily due to isomerization. These changes were associated with modifications in the aromaticity and ionization of the imidazole ring, driven by both metal adsorption and alkaline conditions. Our results indicated the formation of distinct tautomeric forms of the imidazole group, namely the thione and thiol forms, in aqueous solution and on the Ag surface, respectively. Furthermore, the EGT spectra at different concentrations suggested that ionization occurred at lower concentrations. Notably, the SERS spectra of the mushroom fruiting bodies were dominated by prominent bands attributable to EGT, as corroborated by the comparison with the EGT fungal extract and EGT standard. These findings underscore the utility of SERS spectroscopy as a rapid and effective tool for obtaining comprehensive molecular fingerprints, even directly from complex biological matrices such as mushroom fruiting bodies. Full article

A novel approach was carried to prepare trans-CuCl₂L₂ complex with the ligand L, (E)-(4-chlorophenyl)-N-(3-phenyl-4H-1,2,4-triazol-4-yl)methanimine which was formed in situ during the reaction of CuCl₂ with 4-(4-chlorobenzylideneamino)-5-phenyl-2H-1,2,4-triazole-3(4H)-thione. The synthesized compounds were characterized by applying various spectroscopic techniques. The crystal structure of the complex was unambiguously determined using X-ray analysis indicating square planar geometry. Intermolecular H-bonds govern the supramolecular structure of the copper complex. Aromatic rings are stacked in an offset packing due to occurrence of π–π interactions. The structure is further corroborated with a detailed computational investigation. A thione–thiol tautomerism for the triazole compound was also studied. The Schiff base 1,2,4-triazole copper chloride complex is expected to have high anticancer activity. Full article

Four different new Schiff basses tethered indolyl-triazole-3-thione hybrid were designed and synthesized. X-ray single crystal structure, tautomerism, DFT, NBO and Hirshfeld analysis were explored. X-ray crystallographic investigations with the aid of Hirshfeld calculations were used to analyze the molecular packing of the studied systems. The H···H, H···C, S···H, Br···C, O···H, C···C and N···H interactions are the most important in the molecular packing of 3. In case of 4, the S···H, N···H, S···C and C···C contacts are the most significant. The results obtained from the DFT calculations indicated that the thione tautomer is energetically lower than the thiol one by 13.9545 and 13.7464 kcal/mol for 3 and 4, respectively. Hence, the thione tautomer is the most stable one which agree with the reported X-ray structure. In addition, DFT calculations were used to compute the electronic properties while natural bond orbital calculations were used to predict the stabilization energies due to conjugation effects. Both compounds are polar where 4 (3.348 Debye) has a higher dipole moment than 3 (2.430 Debye). Full article

The emergence of bacteria that co-express serine- and metallo- carbapenemases is a threat to the efficacy of the available β-lactam antibiotic armamentarium. The 4-amino-1,2,4-triazole-3-thione scaffold has been selected as the starting chemical moiety in the design of a small library of β-Lactamase inhibitors (BLIs) with extended activity profiles. The synthesised compounds have been validated in vitro against class A serine β−Lactamase (SBLs) KPC-2 and class B1 metallo β−Lactamases (MBLs) VIM-1 and IMP-1. Of the synthesised derivatives, four compounds showed cross-class micromolar inhibition potency and therefore underwent in silico analyses to elucidate their binding mode within the catalytic pockets of serine- and metallo-BLs. Moreover, several members of the synthesised library have been evaluated, in combination with meropenem (MEM), against clinical strains that overexpress BLs for their ability to synergise carbapenems. Full article

With the goal of obtaining a novel bioactive compound with significant antifungal activity, a series of 1,3,4-thiadiazole derivatives (3a–3l) were synthesized and characterized. Due to thione-thiol tautomerism in the intermediate compound 2, type of substitution reaction in the final step was determined by two-dimensional (2D) NMR. In vitro antifungal activity of the synthesized compounds was evaluated against eight Candida species. The active compounds 3k and 3l displayed very notable antifungal effects. The probable mechanisms of action of active compounds were investigated using an ergosterol quantification assay. Docking studies on 14-α-sterol demethylase enzyme were also performed to investigate the inhibition potency of compounds on ergosterol biosynthesis. Theoretical absorption, distribution, metabolism, and excretion (ADME) predictions were calculated to seek their drug likeness of final compounds. The results of the antifungal activity test, ergosterol biosynthesis assay, docking study, and ADME predictions indicated that the synthesized compounds are potential antifungal agents, which inhibit ergosterol biosynthesis probably interacting with the fungal 14-α-sterol demethylase. Full article

The synthesis of 4-chloro-8-methylquinolin-2(1H)-one and its thione analogue is described. Some nucleophilic substitution reactions of the 4-chloro group were carried out to get new 4-substituted 2-quinolinones and quinolinethiones, such as 4-sulfanyl, hydrazino, azido and amino derivatives, which are of important synthetic use. The structure of the new compounds was established by their elemental analysis, IR and ¹H-NMR spectra. Also the mass fragmentation pattern of some products is discussed. Full article