Search Results (150)

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

Transition metal complexes bearing protic N-heterocyclic carbene (pNHC) ligands are promising precatalysts for organic reactions due to their capacity for unique hydrogen-bonding interactions. Herein, we report the synthesis and structural characterization of the first Pd(II) complex featuring a pNHC derived from 1,2,4-triazole—a heterocyclic system previously unexplored for the preparation of metal/pNHC complexes. The complex was synthesized via oxidative addition of 3-bromo-5-cyclohexyl-1-methyl-1H-1,2,4-triazole to Pd(PPh₃)₄ in the presence of NH₄BF₄. Its molecular structure was characterized by NMR spectroscopy and X-ray diffraction analysis. Full article

This paper introduces the nitration process of obtaining the synthetic intermediate 1-(2-chloro-4-fluoro-5-nitrobenzene)-4-difluoromethyl-4,5-dihydro-3-methyl-1,2,4-triazol-5(1H)-one of pyraclostrobin using raw materials fluorobenzotriazolone, fuming nitric acid, fuming sulfuric acid, and toluene. The exothermic characteristics of the nitration, quenching, extraction, and alkali washing in the nitration reaction were studied, and the thermal decomposition risk of the raw materials and the secondary decomposition risk of the products in the nitration process were evaluated. The results showed that the thermal decomposition risk of the four raw materials was level 1. The acceptable level of runaway reaction in the nitration process was evaluated to be level 2, the acceptable level of runaway reaction in the quenching was level 3, the acceptable level of runaway reaction in the extraction and the alkali washing was level 1, the process hazard level of the nitration reaction and the quenching was evaluated to be level 5, and the process hazard level of the extraction and the alkali washing was level 1. Based on the comprehensive assessment results, targeted risk mitigation and control strategies are proposed to ensure process safety. 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

Background/Objectives: In this study, a novel series of 4-(arylchalcogenyl)methyl)-1H-1,2,3-Triazol-1-yl-menadione derivatives were synthesized to explore their potential as new antituberculosis (anti-TB) agents. Selenium-containing compounds are known for their significant antimycobacterial activity, which motivated their inclusion in the design. Methods: The target compounds were synthesized via a copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, affording yields ranging from 34% to 93%. All compounds were evaluated in vitro for anti-TB activity against Mycobacterium tuberculosis H37Rv (ATCC 27294), as well as a drug-resistant strain (T113/09). Results: Several selenium-containing derivatives exhibited promising activity. Compounds 9b and 9g were equipotent to the first-line anti-TB drug, and one compound surpassed its activity. Notably, compounds 9a, 9b, 9g, and 9h also showed efficacy against the INH- and RIF-resistant Mtb strain T113/09. Conclusions: The efficacy of selenium-containing triazole-menadione hybrids against both sensitive and resistant Mtb strains highlight their potential as candidates for addressing antimicrobial resistance in TB treatment. Further investigations are required to understand their mechanisms of action and assess their in vivo therapeutic potential.. Full article

The synthesis of (E)-1-(1-benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-3-phenyl-2-propen-1-one derivatives was carried out in two steps, using benzylic chloride derivatives as starting material. The structural determination of intermediates and final products was performed by spectroscopic methods: infrared spectroscopy, nuclear magnetic resonance spectroscopy and mass spectrometry (IR, NMR, and MS). In vitro evaluation of cytotoxic activity on adherent and non-adherent cells showed that triazole chalcones exhibited significant activity against three of the five cell lines studied: non-Hodgkin lymphoma U937, glioblastoma multiform tumor T98G, and gallbladder cancer cells Gb-d1. In contrast, the cytotoxic activity observed for cervical cancer HeLa and gallbladder adenocarcinoma G-415 was considerably lower. Additionally, in the cell lines where activity was observed, some compounds demonstrated an In vitro inhibitory effect superior to that of the control, paclitaxel. Molecular docking studies revealed specific interactions between the synthesized ligands and therapeutic targets in various cell lines. In U937 cells, compounds 4a and 4c exhibited significant inhibition of vascular endothelial growth factor receptor (VEGFR) kinase, correlating with their biological activity. This effect was attributed to favorable interactions with key residues in the binding site. In T98G cells, compounds 4r and 4w showed affinity for transglutaminase 2 (TG2) protein, driven by their ability to form hydrophobic interactions. In Gb-d1 cells, compounds 4l and 4p exhibited favorable interactions with mitogen-activated protein kinase (MEK) protein, similar to those observed with the known inhibitor selumetinib. In HeLa cells, compounds 4h and 4g showed activity against dihydrofolate reductase (DHFR) protein, driven by hydrogen bonding interactions and favorable aromatic ring orientations. On the other hand, compounds 4b and 4t exhibited no activity, likely due to unfavorable interactions related to halogen substitutions in the aromatic rings. Full article

Two new Cu(II) (CP1) and Co(II) (CP2) coordination polymers (CPs) with the triazole ligand 5-methyl-1-(pyridin-4-yl-methyl)-1H-1,2,3-triazole-4-carboxylate (L1) have been synthesized and structurally characterized by SCXRD (Single Crystal X-Ray Difraccion), PXRD (Power X-Ray Difracction), FT-IR (Fourier Transform Infrared), TG (Theermo Gravimetric), and electrochemical techniques. Both CPs were obtained at the water/n-butanol interface by reacting nitrate salts of each metal with the NaL1 ligand. SCXRD analysis revealed that CP1 (Coordination Polymer 1) and CP2 (Coordination Polymer 2) crystallize in the monoclinic space groups C2/c (No. 15) and P2₁/n (No. 14), respectively, forming 1D zigzag chain structures, which further lead to a 2D supramolecular network through O-H⋯O and C-H⋯O hydrogen bond interactions, respectively. In CP1, the supramolecular structure is assembled by hydrogen bonds involving water molecules. In contrast, CP2 forms its supramolecular network mainly through hydrogen bonds between adjacent triazole ligand molecules. Hirshfeld surface analysis revealed that the most significant contributions to the crystal packing come from H⋯O/O⋯H, H⋯H, H⋯N/N⋯H, and H⋯C/C⋯H interactions. In addition, FT-IR provided information on the functional groups involved in the coordination, while the decomposition patterns of both CPs were evaluated by TGA. Electrochemical studies conducted in a saline environment showed that CP1 exhibits superior hydrogen evolution reaction (HER) kinetics compared to CP2, as evidenced by a higher exchange current density and a lower Tafel slope. Density functional theory calculations and experimental bandgap measurements provided a deeper understanding of the electronic properties influencing the electrochemical behavior. The results highlight the potential of CP1 as an efficient catalyst for HER under saline conditions. Full article

This research focuses on the removal of emerging contaminants (CEC) present in synthetic aqueous matrices. Azole compounds were selected as CEC of interest due to their persistence and toxicity, particularly the triazole and oxazole groups. These compounds are also trace contaminants listed in the proposed revision of Directive 91/271/EEC on urban wastewater treatment and the 3rd European Union Observation List (Implementing Decision EU 2020/116), highlighting their regulatory importance. The draft Directive includes the implementation of quaternary treatments to achieve the highest possible removal rates of micropollutants. Among the technologies used on a large scale are some advanced oxidation processes (AOP), often combined with adsorption on activated carbon (AC). Laboratory-scale pilot plants have been designed and operated in this research, including UV photolysis and oxidation with H₂O₂ and adsorption with GAC. The results demonstrate that UV photolysis is able to remove all the selected CECs except fluconazole, reaching eliminations higher than 86% at high doses of 31.000 J/m². Treatment by H₂O₂ achieved removals of 4 to 55%, proving to be ineffective in the degradation of persistent compounds when acting as a single technology. Adsorption by AC is improved with longer contact times, reaching removals above 80% for benzotriazole and methyl benzotriazole at short contact times, followed by sulfamethoxazole and tebuconazole. Fluconazole had a mean adsorption capacity at low contact times, while metconazole and penconazole showed low adsorption capacities. Full article

Background: In the era of resistance, the design and search for new “small” molecules with a narrow spectrum of activity that target a protein or enzyme specific to a certain bacterium with high selectivity and minimal side effects remains an urgent problem of medicinal chemistry. In this regard, we developed and successfully implemented a strategy for the search for new hybrid molecules, namely, the not broadly known [2-(3-R-1H-[1,2,4]-triazol-5-yl)phenyl]amines. They can act as “building blocks” and allow for the introduction of certain structural motifs into the desired final products in order to enhance the antistaphylococcal effect. Methods: The “one-pot” synthesis of the latter is based on the conversion of substituted 4-hydrazinoquinazolines or substituted 2-aminobenzonitriles and carboxylic acid derivatives to the target products. The possible molecular mechanism of the synthesized compounds (DNA gyrase inhibitors) was investigated and discussed using molecular docking, and their further study for antistaphylococcal activity was substantiated. Results: A significant part of the obtained compounds showed high antibacterial activity against Staphylococcus aureus (MIC: 10.1–62.4 µM) and 5-bromo-2-(3-(furan-3-yl)-1H-1,2,4-triazol-5-yl)aniline and 5-fluoro-2-(3-(thiophen-3-yl)-1H-1,2,4-triazol-5-yl)aniline, with MICs of 5.2 and 6.1 µM, respectively, approaching the strength of the effect of the reference drug, “Ciprofloxacin” (MIC: 4.7 µM). The conducted SAR and ADME analyses confirm the prospects of the further structural modification of these compounds. The obtained [2-(3-R-1H-[1,2,4]-triazol-5-yl)phenyl]amines reveal significant antimicrobial activity and deserve further structural modification and detailed study as effective antistaphylococcal agents. The SAR analysis revealed that the presence of a cycloalkyl or electron-rich heterocyclic fragment in the third position of the triazole ring was essential for the antibacterial activity of the obtained compounds. At the same time, the introduction of a methyl group into the aniline moiety led to an enhancement of activity. The introduction of halogen into the aniline fragment has an ambiguous effect on the level of antistaphylococcal activity and depends on the nature of the substituent in the third position. Conclusions: Obtained [2-(3-R-1H-[1,2,4]-triazol-5-yl)phenyl]amines reveal significant antistaphylococcal activity and deserve for further detailed study as effective antibacterial agents. Full article

The overexpression of the epidermal growth factor receptor (EGFR) in certain types of prostate cancers and glioblastoma makes it a promising target for targeted radioligand therapy. In this context, pairing an EGFR-targeting peptide with the emerging theranostic pair comprising the Auger electron emitter cobalt-58m (^58mCo) and the Positron Emission Tomography-isotope cobalt-55 (⁵⁵Co) would be of great interest for creating novel radiopharmaceuticals for prostate cancer and glioblastoma theranostics. In this study, GE11 (YHWYGYTPQNVI) was investigated for its EGFR-targeting potential when conjugated using click chemistry to N1-((triazol-4-yl)methyl)-N1,N2,N2-tris(pyridin-2-ylmethyl)ethane-1,2-diamine (TZTPEN). This chelator is suitable for binding Co²⁺ and Co³⁺. With cobalt-57 (⁵⁷Co) serving as a surrogate radionuclide for ^55/58mCo, the novel GE11-TZTPEN construct was successfully radiolabeled with a high radiochemical yield (99%) and purity (>99%). [⁵⁷Co]Co-TZTPEN-GE11 showed high stability in PBS (pH 5) and specific uptake in EGFR-positive cell lines. Disappointingly, no tumor uptake was observed in EGFR-positive tumor-bearing mice, with most activity being accumulated predominantly in the liver, gall bladder, kidneys, and spleen. Some bone uptake was also observed, suggesting in vivo dissociation of ⁵⁷Co from the complex. In conclusion, [⁵⁷Co]Co-TZTPEN-GE11 shows poor pharmacokinetics in a mouse model and is, therefore, not deemed suitable as a targeting radiopharmaceutical for EGFR. Full article

The use of the concept of privileged structures significantly accelerates the search for new leads and their optimization. 6-(methylsulfonyl)-8-(4-methyl-4H-1,2,4-triazol-3-yl)-2-(5-nitro-2-furoyl)-2,6-diazaspiro[3.4]octane 1 has been identified as a lead, with MICs of 0.0124–0.0441 μg/mL against MTb multiresistant strains. Several series of structural analogues have been synthesized, including variations in the periphery and simplifications of their scaffolds. All synthesized compounds were tested against the MTb H37Rv strain and ESKAPE panel of pathogens using serial broth dilutions. However, an attempt to optimize structure of 1 did not lead to the development of more active compounds which can work against MTb, but to substances with high activity against S. aureus. Induced-fit docking and MM-GBSA calculations determined a change in the likely biotarget from deazaflavin-dependent nitroreductase to azoreductases. The privileged nature of the scaffold was demonstrated by the detection of a different type of activity. Full article

Influenza is a disease of significant morbidity and mortality. The number of anti-influenza drugs is small; many of them stimulate the appearance of resistant strains. This article presents the results of assessing the antiviral activity of 1,2,3-triazole-containing derivatives of alkaloid lupinine for their ability to suppress the reproduction of orthomyxoviruses (influenza viruses: A/Vladivostok/2/09 (H1N1) and A/Almaty/8/98 (H3N2)). The ability of (1S,9aR)-1-[(1,2,3-triazol-1-yl)-methyl]octahydro-1H-quinolizines with aryl-, 4-((4-formylphenoxy)methyl)- or 4-((3-tert-butyl-5-ethyl-2-hydroxy-benzoyloxy)methyl)- substituents at the C-4 position of the triazole ring to reduce the infectivity of the virus when processing virus-containing material was established, indicating good prospects for the studied compounds as virucidal agents affecting extracellular virions. The experimental results demonstrated that the triazolyl lupinine derivatives exhibited varying degrees of affinity for both hemagglutinin and neuraminidase proteins. Furthermore, these compounds demonstrated inhibitory effects on the replication of influenza viruses with different antigenic subtypes. The obtained biological data are in agreement with the results of molecular docking, which showed strong binding energies of the investigated compounds under study with biological targets—hemagglutinin and neuraminidase proteins. Following the evaluation of antiviral efficacy among the studied triazolyl derivatives of lupinine, four compounds have been identified for subsequent comprehensive in vitro and in vivo investigations to further elucidate their antiviral properties. Full article

At the current stage of organic chemistry development, various fundamental synthetic approaches have been developed for the synthesis of 1,2,4-triazole and pyrimidine scaffolds, which demonstrate diverse biological effects. The relevance of this research lies in the combination of two pharmacophore fragments in one molecule—a pyrimidine and an azole heterocycle—connected by a thiomethylene bridge, which is expected to improve solubility and enhance known biological properties, as well as introduce new ones. This study presents the synthesis of compounds and investigates their antiradical activity applying the DPPH free radical method. Three compounds demonstrate greater activity than the reference drug, the natural antioxidant ascorbic acid. Full article

Cu(II) and Mn(II) coordination polymers [Cu(ttpa)(sub)]_n (Cuttpa or 1) and {[Mn₂(ttpa)₂(nip)₂(H₂O)₂]·3H₂O}_n (Mnttpa or 2) (ttpa = tris(4-(1,2,4-triazol-1-yl)phenyl)amine, H₂sub = suberic acid, nip = 5-nitroisophthalicate) were hydrothermally prepared and the structures were characterized. Cuttpa exhibited a 2D (4,4) network based on [Cu₂(COO)₄] dimers with upper and lower dangled ttpa ligands and a 2D → 3D polythreaded network. Mnttpa showed a 2D (4,4) network with dangled uncoordinated triazole rings from ttpa ligands and nitro groups from nip²⁻ ligands and a 2D → 3D polythreaded network. E_g data of Cuttpa and Mnttpa were 1.88 eV and 2.11 eV. Cuttpa and Mnttpa exhibited good catalytic activity for the decomposition of methyl blue (MB) under visible light and supersound irradiation. The decomposition mechanism using Cuttpa was explored. The holes (h⁺) and ^•OH hydroxyl radicals played the main roles, and the ^•O₂⁻ superoxide radicals played certain auxiliary roles in the decomposition of MB within the Cuttpa catalyst. Full article