Search Results (1,579)

The anti-inflammatory scaffold 5-aminosalicylic acid, which is widely used in therapeutic applications, was chosen for the synthesis of N-[3-(hydrazinecarbonyl)-4-hydroxyphenyl]acetamide (1) to enhance its antibacterial properties. The condensation of hydrazide 1 with aromatic aldehydes provided hydrazone derivatives 2a–f, whereas cyclocondensation reactions and other related transformations afforded five-membered heterocycles, including pyrrole 3, pyrazole 4, pyrrolidinone 7, oxadiazoles 9, 10, thiadiazole 14, and triazole 15. Additional modifications yielded acetylhydrazine derivative 11, which was O-alkylated to analogue 12. Antibacterial evaluation showed stronger activity against Gram-positive bacteria such as S. aureus and MRSA than against Gram-negative strains of E. coli and S. Enteritidis, consistent with differences in cell membrane permeability. Notably, derivatives containing pyrrolidinone 7, thiosemicarbazide 13, and 1,3,4-thiadiazole 14 exhibited potent bactericidal activity against S. aureus and MRSA, while hydrazones 2b, 2c, 2f, pyrrole 3, and pyrrolidinone 7 exhibited activity against E. coli. These results provide a practical strategy for the discovery of heterocyclic compounds and emphasise the potential of functionalised 5-aminosalicylic acid derivatives as prime candidates for the development of broad-spectrum antibacterial agents. Full article

We developed an efficient and modular route to 2- and 6-(1,2,3-triazol-1-yl)azulenes to expand the synthetic accessibility and functional scope of azulene-based π-systems with stimulus-responsive photophysics. Readily accessible 2- and 6-azidoazulenes, prepared in excellent yields via S_NAr reactions of haloazulenes, were subjected to Cu(I)-catalyzed Huisgen [3 + 2] cycloaddition with a broad range of terminal alkynes to afford the corresponding triazolylazulenes in good to high yields, followed by acid-mediated decarboxylation and Staudinger reduction to enable further diversification to 2-azulenyltriazoles and a 6-aminoazulene derivative. Single-crystal X-ray diffraction analysis revealed substitution-position-dependent torsional arrangements and variations in π-conjugation between the azulene and triazole units. Photophysical characterization by UV/Vis absorption and fluorescence spectroscopy showed pronounced halochromism under acidic conditions, and selected derivatives displayed substantially enhanced fluorescence quantum yields. Overall, these results establish the azulene–1,2,3-triazole motif as a versatile building block for designing optoelectronic π-systems with acid-responsive emission properties. 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

Fusarium head blight (FHB), caused mainly by the Fusarium graminearum species complex, is a devastating cereal disease associated with yield losses and mycotoxin contamination. Early infection is closely linked to spore germination and germ tube elongation, yet conventional monitoring methods are labor-intensive and poorly suited for dynamic phenotypic quantification. We present EffiFormer-CGS, a three-module deep learning framework integrating object detection, key point localization, and phenotypic quantification for microscopic images of FHB spores. A dataset of 2381 images was generated from systematic experiments with triazole fungicides (Prochloraz, Prothioconazole, and Tebuconazole) across multiple concentrations and time points. Spores were annotated with bounding boxes and fine-grained geometric key points, enabling calculation of germination degree as the ratio of germ tube length to body length. EffiFormer-CGS achieved 90.8% mAP@0.5:0.95 in object detection and 91.4% mAP@0.5 in key point localization. All fungicides significantly inhibited germination, with Prochloraz showing the strongest effect. Predictions closely matched manual counts, with germination rate errors ≤ 5.18%. EffiFormer-CGS provides an efficient, automated, and high-precision approach for spore germination analysis, supporting high-throughput fungicide screening, resistance monitoring, and sustainable FHB management. Full article

Background/Objectives: Leishmaniasis constitutes one of the most fatal parasitic diseases globally, adversely impacting the health of individuals residing in both intertropical and temperate zones. In these geographical areas, the administration of treatment is often inconsistent and largely ineffective with the available pharmaceuticals, as these exhibit more pronounced side effects than the therapeutic advantages they purport to provide. Methods: Consequently, the current investigation seeks to engage in molecular modeling of novel pharmacological candidates incorporating 1,2,3 disubstituted triazole moieties, coordinated with Cu^II metal centers, in pursuit of promising bioactive properties. Results: Two complexes were prepared and X-ray analysis revealed a comparable structural configuration surrounding the copper (II) atom. The planar square coordination geometry was elucidated through the assessment of the ${\tau }_4=0$ (tau four) parameters. The comprehensive characterization encompasses HRMS-ESI (+), NMR, elemental analyses, mid-infrared, and UV-vis spectroscopic techniques. Time-dependent density functional theory (TD-DFT) analyses will substantiate the findings obtained through UV-vis spectroscopy. Crucially, the biological assays against Leishmania (L.) amazonensis revealed that Complex 1 exhibited outstanding potency against the intracellular amastigote form, demonstrating a half-maximal inhibitory concentration (IC₅₀) of 0.4 µM. This activity was 6-fold higher than that of amphotericin B (IC₅₀ = 2.5 µM) and 33-fold higher than pentamidine (IC₅₀ = 13.3 µM). Furthermore, Complex 1 showed a promising selectivity index (SI = 9.7) against amastigotes, surpassing the reference drugs and meeting the criteria for a lead compound. While less active on promastigotes, both complexes demonstrated high stability in DMSO solution, a prerequisite for biological testing. Conclusions: These results unequivocally identify Complex 1 as a highly promising candidate for the development of new antileishmanial therapies, warranting further in vivo studies. Full article

A collection of 40 derivatives of 1,2-diphenyl-2-[1,2,3]triazol-1-yl-ethanol was obtained through a sequence of reactions, starting with benzoin as the initial raw material and using the CuAAC reaction as the key step in this process. The structure of a pair of these compounds was ultimately corroborated by single-crystal X-ray diffraction studies, which also reveals important O-H···N interactions. The antimicrobial activity of synthesized 1,2,3-triazoles was assessed against strains that include Candida albicans and Staphylococcus aureus. The antiproliferative properties of some of these novel compounds were also tested using a variety of tumor cell lines, including U251 (human glioblastoma), PC-3 (human prostate cancer cell line), K562 (human leukemia), HCT-15 (human colorectal adenocarcinoma), MCF-7 (human breast adenocarcinoma), and SKLU (human lung adenocarcinoma). Full article

This computational study investigates the thermal decomposition of 1,2,4-triazol-3(2H)-ones and their thione analogues using Density Functional Theory (DFT). The reaction proceeds via a concerted, six-membered cyclic transition state, primarily driven by the breaking of the N–N bond. A key finding is that the accuracy of the calculated activation energies (Ea) strongly depends on the choice of DFT functional. For sulfur-containing systems (thiones), the hybrid functional APFD (with 25% Hartree–Fock exchange) provides the most reliable results, effectively describing their higher polarizability. In contrast, for oxygen-containing systems (triazolones), the dispersion-corrected functional B97D-GD3BJ (with 0% Hartree–Fock exchange) delivers superior accuracy by better modeling electrostatic and dispersion interactions. The -CH₂CH₂CN group at the N-2 position acts not only as a protecting group but also stabilizes the transition state through non-covalent interactions. Electron-withdrawing substituents slightly increase the E_a, while electron-donating groups decrease it. Sulfur analogues consistently show significantly lower activation energies (by ~40 kJ/mol) than their oxygen counterparts, explaining their experimentally observed faster decomposition. This work establishes a dual-methodology computational framework for accurately predicting the kinetics of these reactions, providing valuable insights for the regioselective synthesis of biologically relevant triazole derivatives via controlled pyrolysis. Full article

Macrocyclic drugs are promising for targeting undruggable proteins, including those in cancer. Our prior work identified BE-43547A₂ (BE) as a selective inhibitor of pancreatic cancer stem cells in PANC-1 cultures, but its high lipophilicity limits clinical application. To address this, we designed derivatives retaining BE’s backbone while modifying tail groups to improve its properties. A concise total synthesis enabled a versatile late-stage intermediate (compound 17), serving as a platform for efficient diversification of BE analogs via modular click chemistry. This approach introduced a central triazole ring connected by flexible alkyl spacers. Key properties, including lipophilicity, solubility, and Caco-2 permeability, were experimentally determined. These derivatives exhibited reduced lipophilicity and improved solubility but unexpectedly lost cellular activity. Direct target engagement studies using MicroScale Thermophoresis (MST) revealed compound-dependent deactivation mechanisms: certain derivatives retained binding to eEF1A1 with only modestly reduced affinity (e.g., compound 29), while others showed no detectable binding (e.g., compound 31). Microsecond-scale molecular dynamics simulations and free-energy calculations showed that, for derivatives retaining target affinity, tail modifications disrupted the delicate balance of drug–membrane and drug–solvent interactions, resulting in substantially higher transmembrane free-energy penalties (>5 kcal/mol) compared to active compounds (<2 kcal/mol). These insights emphasize the need to simultaneously preserve both target engagement and optimal permeability when modifying side chains in cell-permeable macrocyclic peptides, positioning compound 17 as a robust scaffold for future lead optimization. This work furnishes a blueprint for balancing drug-like properties with therapeutic potency in macrocyclic therapeutics. Full article

Triazole fungicides are used to protect tomato yield from fungal infection. However, information regarding triazole residues and dissipation profiles is limited. This study aimed to evaluate the behavior, residue dissipation, and potential risks of penconazole (PCZ, 10% EC, 25 cm³/100 L water) and difenoconazole (DFZ, 25% EC, 50 cm³/100 L water) applied during the fruiting stage of tomatoes over 15 days in Mit Al-Qurashi village, Dakahlia Governorate, Egypt. The study also examined the residue levels of PCZ and DFZ in tomatoes following household preparation methods, as well as the health risks and residue intake associated with these pesticides. Additionally, the impact of PCZ and DFZ residues on macro- and micro-nutrient levels, as well as quality parameters in tomato fruits, was investigated. Our data showed that PCZ and DFZ exhibited dissipation rates recorded at 70.88% and 73.33% after 6 days of application, then increased to 99.74% and 98.25% after 15 days of application, respectively, corresponding to half-lives of 2.08 and 2.78 days. The pre-harvest intervals (PHIs) were determined to be 9 days for DFZ and 12 days for PCZ. Based on risk assessment and Health Risk Index (HRI) calculations, the withholding periods for using treated tomato fruits for human consumption were extended to 15 days for DFZ treatment and reduced to 9 days for PCZ. Notably, tomato fruits treated with PCZ or DFZ could be safely consumed one day after application if processed into paste. However, other forms of processing, including washing with water, acetic acid (5%), and sodium carbonate (5%) for 5 min, significantly reduced the residue levels of the tested fungicides. Moreover, the tested fungicides not only significantly reduced the levels of macro- and micronutrients in tomato fruits but also altered the quality parameters of the tomatoes. These findings could guide the safe and responsible use of PCZ and DFZ in tomatoes, helping to prevent potential health risks to consumers. Full article

Click chemistry, and particularly the Cu-catalyzed Azide Alkyne Cycloaddition (CuAAC) reaction has gained increased attention in recent years as an invaluable tool for synthesizing pharmaceutical active organic compounds. In this study, quinolinones and triazoles, two bioactive heterocyclic moieties amenable to various substitutions, were employed to design and synthesize novel quinolinone–triazole hybrid molecules via the CuAAC click reaction under microwave irradiation. The synthesized hybrid molecules and their alkyne precursors were structurally characterized and evaluated for their antioxidant capacity, lipoxygenase (LOX) inhibitory activity, cell viability using HaCaT epithelial cells, and cytotoxicity against two cancer lines. The results indicated that, among the precursors, alkyne 4c exhibits the best combined antioxidant and anti-inflammatory activity (100% lipid peroxidation inhibition, IC₅₀ = 22.5 μM for LOX inhibition); among the hybrid molecules, compound 5a was the most potent (98.0% lipid peroxidation inhibition, IC₅₀ = 10.0 μM for LOX inhibition). Regarding the assessment of HaCaT cell viability, all studied compounds showed encouraging results, with cell viability rates between 61.5% and 100%. Moreover, based on the results of the cytotoxicity against cancer lines A549 and A375, it emerged that the tested compounds exhibited moderate–low or no cytotoxicity. These results highlight the potential of quinolinone–triazole hybrids as valuable candidates in drug discovery. Full article

Chagas disease is caused by the protozoan Trypanosoma cruzi, and its current treatment is limited to the use of two nitroderivatives, benznidazole (Bz) and nifurtimox; however, their toxicity often leads to discontinuation, justifying the search for new therapeutic options. The biological activity of quinones has long shown efficacy towards pathogenic microorganisms. In our previous investigations, two naphthoquinones combining ortho- and para-quinoidal moieties exhibited remarkable trypanocidal activity and presented low toxicity to host cells. Here, these two active compounds were further assessed. On trypomastigotes and epimastigotes, brominated (NQ1) and chlorinated (NQ2) nor-beta-lapachone-derived 1,2,3-triazoles were more active than Bz, presenting IC₅₀/24 h values in the range of 0.8 to 3.1 µM. NQ1-treated epimastigotes showed a mitochondrial impairment and reactive oxygen species (ROS) production under electron microscopy and flow cytometry. The in vitro evaluation of both combinations of compounds with Bz indicated an additive interaction. In vivo, oral treatment with NQ1 reduced parasitemia in an acute model, with no evidence of toxicity. The treatment also led to a reduction in myocarditis, decreasing the PR interval in electrocardiographic analysis and reversing the sinus bradycardia caused by infection. These data suggest that T. cruzi mitochondrion are part of the NQ1 mechanism of action. In vivo, this compound presented moderate trypanocidal and promising anti-inflammatory activity. Its combination with Bz could enhance current therapeutic protocols and should be better explored in the future. Full article

Antimicrobial resistance remains a critical global health challenge, and was intensified by the COVID-19 pandemic. To address this growing threat, novel antibacterial agents targeting unconventional mechanisms are urgently needed. One promising strategy involves inhibiting bacterial riboswitches—RNA elements that regulate gene expression. Unlike most riboswitches that respond to small-molecule metabolites, the T-box riboswitch uniquely binds non-aminoacylated tRNA and is predominantly found in Gram-positive bacteria, making it an attractive target due to its conserved sequences and regulatory role over essential genes. This study explored oxazolidinone- and triazole-based compounds as potential inhibitors of the T-box riboswitch. Prior investigations into tricyclic oxazolidinones revealed an allosteric modulator that effectively inhibited T-box riboswitch transcriptional readthrough in vitro, though it showed limited disruption of the isolated tRNA–antiterminator complex. To enhance RNA-binding affinity and stereoselectivity, a macrocyclic oxazolidinone scaffold was designed, incorporating a strategic substituent to expand the interaction footprint. A synthetically viable candidate was identified, and computational docking studies suggested that one of the designed compounds may interfere with tRNA-induced transcription by forming π–π stacking interactions with G5 in the antiterminator region. These findings support the potential of targeting the T-box riboswitch with structurally optimized small molecules as a novel antibacterial strategy. Full article

Purpureocillium lilacinum is an emerging pathogen that can cause severe ocular infections. This study aimed to investigate the risk factors, clinical manifestations, antifungal susceptibilities, and outcomes of ocular infections caused by P. lilacinum at a large ophthalmic center in Southern China. This retrospective study reviewed the medical records of 34 patients with culture-proven P. lilacinum oculomycosis treated at the Zhongshan Ophthalmic Center from January 2020 to December 2024. The study included 34 patients (17 males, 17 females). The most common risk factor was ocular trauma (38.2%). In vitro susceptibility testing revealed high resistance to fluconazole and caspofungin, but general susceptibility to voriconazole (median MIC 0.25 mg/L). Despite 97.1% of patients receiving voriconazole therapy, outcomes were generally poor, with 54.5% of patients experiencing a poor outcome (vision worse than counting fingers). A significantly shorter time to microbiological diagnosis was associated with a favorable outcome (median 26 days vs. 65 days, p = 0.007). In conclusion, the visual outcomes of this infection remain generally poor, with the major clinical challenge being the delay in diagnosis. Therefore, prompt microbiological investigation is recommended for patients with suspected intraocular infection. Voriconazole remains the first-line therapeutic choice, the therapeutic potential of newer triazoles warrants further investigation. Full article

This study details the design, synthesis, and evaluation of a novel series of fourteen 2-((1H-1,2,4-triazol-5-yl)thio)-N-benzylidene-N-arylacetohydrazide hybrid compounds. The primary objective was to investigate their potential as antimicrobial agents and assess their cytotoxicity. A systematic approach combining in silico screening and experimental validation was employed. The initial in silico analysis, using SwissADME, identified compounds with favorable drug-like properties. Subsequently, all fourteen compounds were synthesized and characterized using various spectroscopic methods. Their antibacterial efficacy was evaluated in vitro against Gram-negative (Klebsiella aerogenes) and Gram-positive (Enterococcus sp.) bacteria through growth kinetics and colony-forming unit (CFU) assays. Cytotoxicity was assessed using MTT assays on HEK (human embryonic kidney) cell lines. The compound, 2-((1H-1,2,4-triazol-3-yl)thio)-N′-(2-fluorobenzylidene)-N-phenylacetohydrazide emerged as the most promising candidate, demonstrating broad-spectrum antibacterial activity. These findings highlight the potential of 2-((1H-1,2,4-triazol-5-yl)thio)-N-benzylidene-N-arylacetohydrazide hybrids as a scaffold for developing new antimicrobial agents. Furthermore, this study suggests possible environmental applications for these compounds in antimicrobial resistance (AMR) management. Full article

Coccidioides immitis and C. posadasii are the causative agents of coccidioidomycosis (CM) or Valley Fever, endemic to the alkaline deserts of North and South America. Clinical treatment of CM is predominantly limited to the triazole and polyene drug classes. There are limited therapeutic options for the treatment of CM, most commonly requiring prolonged courses of therapy with established antifungal agents such as azoles and Amphotericin B, which often lead to toxicity and drug resistance. Clearly, there is a need to develop novel and better antifungal drugs against CM. This review examines both repurposed and recently discovered compounds in various stages of development for the treatment of CM. Full article