Search Results (223)

Therapeutic resistance remains a critical obstacle in rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma. Increasing evidence implicates redox adaptation in tumor survival and treatment failure. Here, we investigated the functional role and clinical relevance of catalase, a primary hydrogen peroxide-detoxifying enzyme, in modulating RMS therapeutic response. Integrated transcriptomic analyses revealed that while catalase is overall downregulated in RMS compared to healthy skeletal muscle, elevated expression strongly correlates with high-risk, metastatic disease and poor overall survival. In human RMS cell lines, catalase was detectable, and its pharmacological inhibition using 3-amino-1,2,4-triazole (3-ATA) promoted reactive oxygen species (ROS) accumulation, sensitizing cells to standard chemotherapeutics. Notably, robust catalase upregulation was observed in RMS cell models characterized by intrinsic and acquired radioresistance, with strong immunoreactivity validated on cell-block sections. Immunohistochemical validation across patient specimens revealed generally weak catalase expression in RMS tumors, whereas strong reactivity was observed in a secondary embryonal RMS (ERMS) arisen following chemoradiotherapy for nasopharyngeal carcinoma. Functionally, targeting catalase with 3-ATA restored both radio- and chemosensitivity in radioresistant RMS lines. Furthermore, co-targeting catalase and Akt using sub-toxic doses of 3-ATA and MK-2206 cooperatively enhanced oxidative stress-mediated cytotoxicity in resistant cells. Together, these findings identify catalase as a pivotal driver of adaptive radioresistance and establish dual catalase/Akt targeting as a promising pro-oxidant strategy to overcome radiotherapy resistance in RMS. Full article

Aspergillus fumigatus is the predominant pathogenic fungus responsible for aspergillosis. In recent years, the global detection rate of azole-resistant A. fumigatus has continuously increased, and the extensive application of agricultural azole fungicides has been recognized as a crucial driving factor for the emergence and spread of resistance mutations in environmental A. fumigatus. Previous investigations conducted by our research team in karst vegetable fields of Guizhou Province revealed that the triazole resistance rate of local A. fumigatus was only 0.49%, which was markedly lower than those reported in most previous studies in China and outside of China. To supplement the prevalence data of azole resistance across different habitats in this region, a total of 191 environmental A. fumigatus strains were isolated from nine tea plantations across Guizhou. In this study, two clinically prevalent azole drugs, itraconazole and voriconazole, were used for antifungal susceptibility testing, and the triazole target gene cyp51A of all isolates was sequenced and analyzed. Antifungal susceptibility results demonstrated that the MIC ranges of the tea plantation A. fumigatus population were 0.015–0.5 μg/mL for itraconazole and 0.031–0.25 μg/mL for voriconazole, with no evidence of triazole resistance. Genetic analysis identified ten different gene mutations among 29 isolates, all of which were classified as non-resistance-associated mutations. Among these mutations, four were synonymous mutations, including 267G→A, 540G→A, 1074A→G, and 1362T→C, while six were non-synonymous mutations, including 137T→A, 514A→G, 743A→C, 744T→A, 765C→G, and 1279G→A. These non-synonymous mutations resulted in five amino acid substitutions in 25 strains, namely F46Y, M172V, N248T/K, D255E, and E427K. The N248T/K mutation exhibited the highest mutational frequency of 0.1309 (25/191) and was distributed across all nine sampling sites. Correlation analyses indicated that no significant correlations were observed between all detected variant loci and MICs of isolates to itraconazole and voriconazole. Phylogenetic analysis revealed that the six sequence types of cyp51A in Guizhou tea plantations were broadly intermixed with those from other parts of China and outside of China. We discussed the implications of these results in the management of antifungal resistance. Full article

1,2,4-Triazole derivatives are widely investigated as bioactive heterocyclic compounds with diverse biological properties; however, their potential effects on avian embryonic development remain insufficiently characterized. This study aimed to synthesize selected Mannich-type 1,2,4-triazol-5-one derivatives and evaluate their in vitro biological activities, predicted enzyme interactions, and in ovo hatchability outcomes in broiler embryos. Three derivatives (3a–3c) were synthesized and structurally characterized using Fourier-transform infrared (FT-IR), proton nuclear magnetic resonance (¹H-NMR), and carbon-13 nuclear magnetic resonance (¹³C-NMR) spectroscopy. Their reducing capacity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity, metal-chelating capacity, and antimicrobial activity were evaluated. Molecular docking analyses were performed against carbonic anhydrase II and catalase, using acetazolamide and 3-amino-1,2,4-triazole as reference inhibitors, respectively. For the in ovo assessment, fertilized Ross 308 eggs were allocated to non-injected control, vehicle control, and compound-treated groups. Compounds 3a, 3b, and 3c were administered on incubation day 17 at 20, 10, and 5 mg/egg, respectively, as literature-supported, compound-specific exploratory exposure levels. The compounds exhibited weak reducing capacity, negligible DPPH radical-scavenging activity, pronounced metal-chelating capacity, and selective antimicrobial activity against several bacterial strains, whereas no inhibition was observed against Escherichia coli. Docking analysis predicted favorable interactions with both enzyme targets, with compound 3c showing the most favorable binding energies. Baseline egg weights were comparable among groups, indicating that initial egg weight was unlikely to influence hatchability outcomes. Complete hatch failure occurred in all compound-treated groups, whereas hatchability was observed in the control groups. These findings suggest that the tested derivatives may adversely affect embryonic development under the applied in ovo conditions. Their pronounced metal-chelating capacity, together with the predicted interactions with carbonic anhydrase II and catalase, provides a plausible mechanistic framework for interpreting the observed embryonic outcomes. The molecular docking results complement the experimental findings and provide supportive in silico evidence for these potential interactions. These findings contribute to the limited literature on the in ovo evaluation of synthetic Mannich-type 1,2,4-triazol-5-one derivatives and provide preliminary evidence regarding their embryotoxic potential. Further dose-dependent, mechanistic, histopathological, and enzyme-based studies are required to clarify the biological basis of the observed effects and to guide future evaluation of these compounds in in ovo, biomedical, and veterinary applications. Full article

A simple and cost-effective graphite paste electrode modified with 5-(4-aminophenyl)-4-amino-1,2,4-triazole-3(2H)-thione was developed for the selective voltammetric determination of Cu(II) ions in environmental water samples. The N,S-donor ligand was incorporated into a graphite–polystyrene matrix without the use of nanomaterials, providing a reproducible and straightforward electrode fabrication route. Scanning electron microscopy revealed a rough, porous surface morphology with an enhanced electroactive surface area of 0.065 cm², approximately twice the geometric area. Electrochemical impedance spectroscopy confirmed diffusion-controlled mass transport, while cyclic voltammetry indicated quasi-reversible behaviour of the Cu(II)/Cu(0) redox system with a linear dependence of peak current on the square root of the scan rate. Differential pulse voltammetry under optimised conditions (0.1 mol·L⁻¹ H₂SO₄, pH 1.0–1.2) yielded a linear analytical response over the concentration range of 0.01–0.4 μmol·L⁻¹ (R² = 0.99507), with a limit of detection of 0.02 μmol·L⁻¹ and a limit of quantification of 0.06 μmol·L⁻¹—well below the WHO guideline for copper in drinking water. The sensing mechanism involves selective N,S-bidentate coordination of Cu(II) at the electrode surface, followed by electrochemical reduction, as supported by FT-IR spectroscopic evidence. The sensor demonstrated good selectivity toward Cu(II) in the presence of common interfering metal ions at up to 20-fold excess. The method was successfully validated against ICP-OES (recovery 99.8%, RSD < 0.33%) and confirmed by spike–recovery experiments (99.0–99.5%), confirming its practical applicability for trace-level environmental monitoring. The modified electrode retained approximately 93% of its initial response after 30 consecutive measurements and 91% after 14 days of storage, demonstrating good operational stability. Full article

In this study, a new series of (E)-4-((2-(2-(4-amino-3-methyl-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)acetyl)hydrazono)methyl)phenyl 4-halogenobenzenesulfonates (3a–3d), where 3a = F, 3b = Cl, 3c = Br, and 3d = I, were successfully synthesized via a straightforward synthetic route. The structures of the obtained compounds were fully characterized and confirmed by spectroscopic techniques, including FT-IR, ¹H NMR, and ¹³C NMR, as well as LC-MS/MS analysis. 1,2,4-triazole-based hydrazone derivatives (3a–3d) were investigated using IR and NMR spectroscopy and DFT calculations. Intermolecular interactions, HOMO-LUMO, dipole moment, polarization, first-order hyperpolarizability, and molecular electrostatic potential studies on the molecules were examined. The HOMO and LUMO energy gap study supports the charge transfer probability in the molecules. These were conducted to investigate the reactivity and stability of heterocyclic molecules in bioactivity analysis. Electron density mapping within the molecular electrostatic potential plot and electrostatic potential representation within the iso-surface plot evaluated the concept of charge distribution in the molecule as nucleophilic reactions and electrophilic regions. The predicted nonlinear optical (NLO) properties of the molecules are much greater than those of urea. The results obtained from these investigations collectively provide evidence that the molecules possess nonlinear optical applications. Novel triazole–hydrazone-functionalized aryl sulfonate derivatives (3a–3d) were evaluated for their anticancer potential against a panel of brain and non-brain cancer cell lines. Compound 3b exhibited the most favorable overall biological profile, displaying potent activity against SH-SY5Y neuroblastoma (GI = 7.59 μM) and U87MG glioblastoma cells (GI = 13.85 μM), together with the lowest toxicity toward normal FL fibroblasts (GI = 62.02 μM). Compounds 3c and 3d demonstrated remarkable potency against IDHmut-U87 glioma cells (GI = 3.87 and 3.27 μM, respectively), although their selectivity toward cancer cells was limited. DNA degradation studies revealed substantial fragmentation, particularly in C6 and SH-SY5Y cells, while migration assays indicated reduced cellular motility. Molecular docking studies identified compound 3b as the strongest PI3Kα binder, supporting a possible. In addition, the antimicrobial activities of compounds 3a–3d were evaluated against selected Gram-positive and Gram-negative bacteria as well as Candida species using the broth microdilution method. The compounds exhibited measurable antimicrobial effects with MIC values ranging from 156 to 625 µg/mL, showing moderate growth inhibition against the tested microorganisms. Although the observed activity was lower than that of the reference antimicrobial agents, the results indicate that these triazole–hydrazone derivatives possess a detectable level of antimicrobial activity and provide a basis for further structural optimization. Collectively, the results suggest that compound 3b represents the most promising lead structure due to its balanced combination of potency, selectivity, and predicted target engagement. Molecular docking was performed to evaluate the binding potential of newly synthesized triazole derivatives (3a–3d) against PI3Kα. The docking protocol was validated by re-docking alpelisib, yielding an RMSD of 0.64 Å. Among the tested compounds, 3b showed the most favorable binding energy (−9.94 kcal/mol) and estimated Ki value (52.13 nM), consistent with its superior in vitro activity. Its interactions with key PI3Kα residues, including Val851, Ser854, Met922, and Asp933, support a stable binding mode within the ATP-binding pocket. In silico ADME and toxicity analyses suggested acceptable drug-likeness characteristics, absence of major hepatotoxic, mutagenic, and carcinogenic liabilities, and moderate predicted acute toxicity profiles. These findings suggest that 3b is the most promising derivative for further validation. Full article

A promising direction for the creation of new biologically active derivatives of the alkaloid lupinine is the synthesis of “hybrid molecules” that combine a fragment of the alkaloid and the pharmacophore of 1,2,3-triazole in their structure. From a biological perspective, this work presents the first X-ray diffraction study of a single crystal of (1S,9aR)-1-({4-[4-(Benzyloxy)-3-methoxyphenyl]-1H-1,2,3-triazol-1-yl}methyl)octahydro-2H-quinolizine, a new, recently synthesized 1,2,3-triazole derivative of lupinine. A comparison of theoretically predicted and experimentally observed structural parameters was carried out. The FTIR spectroscopy study and vibrational properties calculations allowed us to interpret the FTIR absorption spectrum and localize specific vibrational modes in quinolizidine, 1,2,3-triazole, and benzene rings. Such information can be fruitful for further characterization of the synthesis process and products. The molecular docking of the compound was performed. It was shown that the studied molecules are capable of interacting with the Mpro binding site via non-covalent and hydrophobic interactions with subsites S3 (Met165, Glu166, Leu167, Pro168) and S5 (Gln189, Thr190, Gln192), which ensure the stabilization of the Mpro substrate. Blocking of the active site of the enzyme in the region of the oxyanion hole does not occur, but stable stacking interactions with the π-system of one of the catalytic amino acids, His41, are observed. Full article

Nucleopeptides (NPs) are unnatural hybrid polymers designed by coupling nucleobases to the side chains of amino acid residues within peptides. In this study, we present the synthesis of an Fmoc-protected nucleobase amino acid (NBA) monomer (Fmoc-1,4-TzlNBA_A) with adenine attached to the side chain of L-homoazidoalanine (Aha) through a 1,4-linked-1,2,3-triazole. The coupling was accomplished by a Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) of Fmoc-Aha and N9-propargyladenine. Subsequently, a homotrinucleopeptide (HalTzl_AAA) containing three 1,4-TzlNBA_A residues was synthesized, using different solid-phase peptide synthesis (SPPS) approaches, and its ability to recognize U-rich motifs of RNAs involved in the HIV replication cycle was studied using circular dichroism (CD) and fluorescence spectroscopy. CD curves confirmed the binding of HalTzl_AAA to U-rich motifs of the transactivation responsive element (TAR UUU RNA HIV-1) bulge and the anticodon stem–loop domain of human tRNALys3 (ASLLys3) by a decrease in the positive ellipticity band intensity around 265 nm during the complexation. 5′-(FAM(6))-labeled TAR UUU and hASLLys3 were used for fluorescence anisotropy binding studies. Fluorescence data revealed that HalTzl_AAA bound TAR’s UUU bulge with a moderate affinity (K_d ≈ 38 µM), whereas the ASLLys3 UUUU-containing loop sequence was recognized with 2.5 times lower affinity (with K_d ≈ 75 µM). Both the standard SPPS method and its variants, which involved the attachment of adenine to the L-Aha side chain using the click reaction during the synthesis on the resin or after the nucleopeptide cleavage, were characterized by a similar efficiency and yield. The CD and fluorescence results demonstrated that HalTzl_AAA recognized the U-rich sequences of the RNAs with moderate and varied affinities. It is likely that both the hydrogen bonds associated with the complementarity of the interacting sequences and the conformational aspects associated with the high conformational dynamics of U-rich motifs are important in the recognition process. The nucleopeptide represents a new class of RNA binders and may be a promising scaffold for the development of new antiviral drugs. Full article

Therapeutic peptides are a unique drug class due to their high-specificity binding with biological targets. However, the low bioavailability of peptides, as well as the lack of enzymatic stability, imposes a number of limitations on their biomedical application. A good strategy by which to overcome these limitations is the use of peptidomimetics, which are able to imitate the binding and activity of peptides both in vitro and in vivo. Peptidomimetics can be obtained by combining natural and synthetic amino acids in a peptide sequence. Various five-membered heterocycles are often used as structural fragments of peptide imitators to fix the chain in a certain conformation and to increase proteolytic stability. The use of 5-aminomethyl-1,2,4-triazole-3-carboxylic acid derivatives as building blocks of peptidomimetic structures may be a very attractive strategy, in which the tautomeric 1,2,4-triazole fragment is capable of flexibly forming hydrogen bonds on the protein surface of the target. In this work, a number of ethyl 5-aminomethyl-1,2,4-triazole-3-carboxylates and their derivatives were synthesized as mimetics of aliphatic amino acids. Their use as building blocks for synthesizing peptidomimetics was demonstrated. In addition, through the use of a panel of pathogenic and model strains of microorganisms and fungi, we demonstrated the lack of independent activity of the amino acid 1,2,4-triazole mimetics synthesized. This similarity of the biological properties of the obtained mimetics and their natural analogues reveals their bioisosterism. The bioisosterism and geometric similarity of 1,2,4-triazole mimetics and natural amino acid highlights the potential of their use as building blocks for therapeutic peptides. Full article

The significance of this study arises from the urgent need to develop new corrosion inhibitors for the oil and gas industry. These inhibitors should be synthesized from readily available raw materials and be capable of providing effective protection for steel structures against corrosion when exposed to technological hydrochloric acid solutions over a wide temperature range (20–100 °C). The search for such environmentally acceptable and cost-efficient inhibitors is crucial for improving the durability and operational safety of oilfield equipment under aggressive acidic conditions. A new high-temperature corrosion inhibitor for steel in hydrochloric acid solutions has therefore been developed. The inhibitor, designated CATA, is the product of chemical condensation between cinnamaldehyde and 3-amino-1,2,4-triazole. Its protective action is based on the formation of an organic layer up to 12 nm thick, strongly bound to the steel surface. The results suggest with high probability that this protective film consists of polymeric products formed through chemical transformation of CATA on the corroding metal surface. It was shown that the addition of CATA significantly suppresses the electrode processes of steel, affecting both cathodic and anodic partial reactions as well as the kinetics of hydrogen permeation. Adsorption of CATA on steel is satisfactorily described by the Temkin isotherm. The free energy of adsorption (−ΔG_ads) was determined to be 54 kJ mol⁻¹, which is characteristic of chemisorption. This unique inhibition mechanism enables effective corrosion protection of steel in HCl solutions over a wide temperature range (20–100 °C). Under the most aggressive experimental conditions (2 M HCl, 100 °C), the addition of 10 mM CATA achieved an inhibition efficiency of 99.6%, with a corrosion rate of 3.3 g m⁻² h⁻¹, which represents an outstanding result. Furthermore, for spring steels, even in hot HCl solutions (20–60 °C), CATA strongly suppresses hydrogen uptake and allows complete preservation of their ductility. Full article

Background/Objective: The present study reports the design, synthesis, and biological evaluation of novel imidazo-triazole derivatives as potential antidiabetic agents. Methods: The novel series was synthesized by treating amino-triazole bearing carboxylic acid with substituted 2-bromo acetophenone and was biologically compared with acarbose under in vitro analysis. Results: Structure–activity relationship (SAR) analysis revealed that among these compounds, remarkable activity was shown by compound 5 (having three hydroxyl substituents) with IC₅₀ value of 6.80 ± 0.10 and 7.10 ± 0.20 µM for α-amylase and α-glucosidase in comparison to reference drug acarbose. To support experimental findings, computational investigations including molecular docking, pharmacophore modeling, molecular dynamics simulations, density functional theory (DFT), and absorption distribution metabolism excretion and toxicity (ADMET) profiling were employed. These studies confirmed the stability of ligand–protein interactions and provided insights into electronic and reactivity features governing enzyme inhibition. Conclusions: Collectively, the integration of in vitro and in silico approaches underscores the potential of novel imidazo-triazole scaffolds as promising leads for the development of safer and more effective therapeutics against diabetes mellitus. Full article

Background/Objectives: Oxidative stress plays a critical role in the development of ocular diseases such as cataracts. Selenium nanoparticles (SeNPs) offer antioxidant benefits with low toxicity. This study aimed to evaluate the antioxidant activity of SeNPs coated with D-α-tocopheryl polyethylene glycol succinate (TPGS) in human lens epithelial (HLE) cells. Methods: SeNPs were synthesised by reducing sodium selenite with ascorbic acid in the presence of TPGS. Physicochemical characterisation was carried out using dynamic light scattering to assess size and surface charge. Antioxidant activity was measured by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Cytocompatibility was assessed on adult retinal pigment epithelial (ARPE-19) and HLE cells using PrestoBlue. Functional antioxidant performance was determined through enzymatic assays for glutathione peroxidase (GPx), thioredoxin reductase (TrxR), and glutathione (GSH), and lipid peroxidation was assessed using malondialdehyde (MDA) quantification. Catalase mimicry was evaluated under 3-amino-1,2,4-triazole (3-AT)-induced inhibition. Results: The optimal SeNP formulation had an average hydrodynamic diameter of 44 ± 3 nm, low PDI (<0.1), and a surface charge of −15 ± 3 mV. These TPGS-SeNPs demonstrated strong radical scavenging (EC₅₀ ≈ 1.55 µg/mL) and were well tolerated by ARPE-19 cells (IC₅₀ = 524 µg/mL), whereas HLE cells had a narrower biocompatibility window (≤0.4 µg/mL, IC₅₀ = 2.2 µg/mL). Under oxidative stress, SeNPs significantly enhanced GPx and TrxR activity but did not affect GSH or MDA levels. No catalase-mimetic activity was observed. Conclusions: TPGS-SeNPs exhibit potent antioxidant enzyme modulation under stress conditions in HLE cells. Although not affecting all oxidative markers, these nanoparticles show promise for non-invasive strategies targeting lens-associated oxidative damage, including cataract prevention. Full article

In this study, a series of novel β-phenylalanine derivatives were synthesised and evaluated for their anticancer activity. The 3-(4-methylbenzene-1-sulfonamido)-3-phenylpropanoic acid (2) was prepared using β-phenylalanine as a core scaffold. The β-amino acid derivative 2 was converted to the corresponding hydrazide 4, which enabled the development of structurally diverse heterocyclic derivatives including pyrrole 5, pyrazole 6, thiadiazole 8, oxadiazole 11, triazoles 9 and 12 with Schiff base analogues 13 and series1,2,4-triazolo [3,4-b][1,3,4]thiadiazines 14. These modifications were designed to enhance chemical stability, solubility, and biological activity. All compounds were initially screened for cytotoxicity against the A549 human lung adenocarcinoma cell line, identifying N-[3-(3,5-dimethyl-1H-pyrazol-1-yl)-3-oxo-1-phenylpropyl]-4-methylbenzenesulfonamide (5) and (E)-N-{2-[4-[(4-chlorobenzylidene)amino]-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]-1-phenylethyl}-4-methylbenzenesulfonamide (13b) as the most active. The two lead candidates were further evaluated in H69 and H69AR small cell lung cancer lines to assess activity in drug-sensitive and multidrug-resistant models. Schiff base 13b containing a 4-chlorophenyl moiety, retained potent antiproliferative activity in both H69 and H69AR cells, comparable to cisplatin, while compound 5 lost efficacy in the resistant phenotype. These findings suggest Schiff base derivative 13b may overcome drug resistance mechanisms, a limitation commonly encountered with standard chemotherapeutics such as doxorubicin. These results demonstrate the potential role of β-phenylalanine derivatives, azole-containing sulphonamides, as promising scaffolds for the development of novel anticancer agents, particularly in the context of lung cancer and drug-resistant tumours. Full article

In this study, a C-C bond-linked triazole-fused oxadiazole energetic compound, 4-amino-5-(4-amino-1,2,5-oxadiazol-3-yl)-2,4-dihydro-3H-1,2,4-triazol-3-one (1), was successfully designed and efficiently synthesized. Following nitration, a functional group-modified nitramine energetic compound (2) was obtained, and its energetic ionic salt (3) was further prepared. A comprehensive characterization of the structures of these three compounds was conducted, resulting in the successful elucidation of the single-crystal structures of compound 2·Ca²⁺·6H₂O and compound 3·MeOH. Compound 2 exhibited a positive formation enthalpy (56.2 kJ·mol⁻¹) and moderate mechanical sensitivity (FS = 120 N, IS = 12 J). Due to the presence of the nitramine group, compound 2 exhibited a relatively low thermal decomposition temperature (T_dec = 94 °C). However, the thermal stability of compound 3 was significantly improved (T_dec = 233 °C), which is attributed to salt formation. Compound 3 exhibits a positive formation enthalpy (121.0 kJ·mol⁻¹), along with excellent detonation performance (D = 8120 m·s⁻¹, P = 32.1 GPa) and reduced mechanical sensitivity (FS = 224 N, IS = 24 J). Therefore, the multi-heterocyclic compound, joined via C-C bond linkage, demonstrates outstanding performance, offering a new avenue for the design and synthesis of energetic materials. Full article

Compounds containing the pentazolate anion (cyclo-N₅⁻) represent a distinctive group of energetic materials that have received extensive attention in recent years. Cyclo-N₅⁻ was used as a polynitrogen anion for the syntheses of energetic salts through metathesis reactions. Propamidinium (1), 5-amino-4-carbamoyl-1H-imidazol-3-ium (2), (1H-1,2,3-triazol-4-yl)methanaminium (3), 5-amino-4H-1,2,4-triazol-1-ium (4), 5-amino-3-methyl-4H-1,2,4-triazol-1-ium (5), and amino(pyrimidin-2-yl)methaniminium (6) pentazolates were obtained with high yields (>80%), and their crystal structures were confirmed through single-crystal X-ray diffraction analyses. Hirshfeld surface analyses and 2D fingerprint plots generated by CrystalExplorer17 demonstrated that these compounds exhibited extensive hydrogen-bonding networks in their crystal packing. Mechanical sensitivity tests showed that all the prepared salts were highly insensitive (IS > 35 J, FS > 360 N), providing valuable insights for the further exploration of broader energetic materials containing cyclo-N₅⁻. Full article

The synthesis of a new acyclic and cyclic series of D-Ala-AMP analogues was reported. Chemical modifications were introduced on the carbohydrate, the sulfamate linker, and/or the amino-acid N-terminal moiety in order to increase in vivo stability and cell permeability. These new compounds were evaluated in vitro as DltA inhibitors and also in vivo as adjuvant antibiotics to re-sensitize methicillin-resistant Staphylococcus aureus. Indeed, we showed that seven nucleosides containing either a fluorine atom, an azido group, a difluorophosphonylated allylic ether moiety onto the 2′-position, or a sulfamate and a triazole as the sulfamate linker had moderate to excellent IC₅₀ values. Among all these new DltA inhibitors, two molecules functionalized by the fluorinated ether or the sulfamide linker were able to efficiently re-sensitize MRSA to imipenem. Quantification of D-alanyl esters confirmed that these two compounds reduced the level of bacterial cell wall D-alanyl residues by 50% and 80%. Full article