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In this study, the compound 1-(4-methylpiperazin-1-yl-methyl)-3-benzyl-4-(4-hydroxybenzylideneamino)-4,5-dihydro-1H-1,2,4-triazol-5-one (MBHT), synthesized using the Mannich reaction, was comprehensively investigated using theoretical methods. The stable geometry of the molecule was optimized using the B3LYP and B3PW91 functionals within the framework of density functional theory (DFT) and with the basis set 6-311G(d,p). Structural characterization was performed by determining the functional groups using FT-IR spectroscopy and by detailed investigation of the proton and carbon environments using 1H-NMR and 13C-NMR spectroscopies. Theoretical IR and NMR data were calculated using Gaussian 09W software and the GIAO method; the obtained results were validated by comparing them with experimental findings. The molecule's electronic structure was evaluated in detail through parameters such as HOMO–LUMO energy levels and energy gap, Natural Bond Orbital (NBO) analysis, nonlinear optical (NLO) properties, molecular electrostatic potential (MEP) maps, and Mulliken charge distributions. These analyses provided information about MBHT's electron distribution, reactivity profile, and potential interaction sites. Furthermore, molecular docking studies were performed using PDB:5HS1 and PDB:5EQB proteins to investigate its in-silico potential for biological interaction with candidiasis. In the final part of the study, ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis was conducted to evaluate MBHT as a drug candidate. The findings reveal both the structural and electronic properties of MBHT, as well as its potential for interaction with biological targets, providing important information regarding the compound's suitability for the drug development process.

In this study, 1-(4-metilpiperazin-1-il-metil)-3-p-klorobenzil-4-(4-hidroksibenzilidenamino)-4,5-dihidro-1H-1,2,4-triazol-5-on (PCHT), a Mannich base derived from 1,2,4-triazole, was synthesized and its structural properties were investigated using both experimental and theoretical methods. The structure of the compound was experimentally characterized by FT-IR, ¹H-NMR, and ¹³C-NMR spectroscopic techniques. Geometric optimization of the molecule was performed using Density Functional Theory (DFT) with B3LYP and B3PW91 functionals and the 6-31G(d,p) basis set. Theoretical vibrational frequencies and FT-IR, ¹H-NMR and ¹³C-NMR NMR isotropic chemical shift values were calculated via the GIAO method and compared with the experimental data. Furthermore, electronic parameters such as Mulliken atomic charges, HOMO–LUMO energy levels, energy gap (ΔEg), dipole moment, ionization potential, electron affinity, chemical hardness, chemical softness, and electronegativity were calculated. Molecular electrostatic potential (MEP) surface maps were generated to identify the reactive sites of the molecule, and nucleophilic and electrophilic regions were analyzed. In addition, Natural Bond Orbital (NBO) analysis was conducted to examine the electronic structure in more detail, evaluating donor–acceptor interactions and hyperconjugation effects. To investigate the biological activity potential, molecular docking studies were performed, and the binding energies and molecular interactions between the ligand and the target protein were examined. Lastly, the compound's pharmacokinetic properties were assessed using ADMET analysis, which highlighted the molecule's possible drug-like qualities by looking at factors like Lipinski's "rule of five," bioavailability, water solubility, gastrointestinal absorption, and blood-brain barrier permeability.

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.

Among heterocyclic compounds, 1,2,4-triazoles are valuable chemical structures known for their broad spectrum of biological activities and unique roles in medicinal chemistry applications, especially in drug development processes. In this study, eight 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-one derivatives were synthesized and reacted with 3-nitrobenzoyl chloride to obtain N-[3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-one-4-yl]-3-nitrobenzamide derivatives. Subsequently, the amide derivatives underwent Mannich reactions with formaldehyde and morpholine, resulting in four N-Mannich bases. The structures of a total of 12 synthesized compounds were elucidated using IR, 1H-NMR and 13C-NMR spectroscopic techniques. The biological activities of the compounds were evaluated in vitro. Antioxidant properties were assessed using reducing power, free radical scavenging, and metal chelating activity assays. Additionally, antimicrobial activities were tested against five microorganisms (Bacillus cereus, Klebsiella pneumoniae, Staphylococcus aureus, Serratia marcescens, and Candida albicans) using the agar well diffusion method. The results indicated that the compounds exhibited weak antioxidant activity, while some demonstrated notable antimicrobial effects.

1,2,4-Triazoles, recognized for their remarkable therapeutic potential, play a significant role in drug development due to their chemical stability and interaction with various biological targets. In this study, 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-one compunds were reacted with Succinyl Chloride to produce six N,N'-di[3-alkyl(aryl)-4,5-dihydro-1H-1,2,4-triazol-5-one-4-yl]succinylamide derivatives. These derivatives were further modified via the Mannich reaction with formaldehyde and morpholine, yielding three N-Mannich derivatives. Structural characterization of nine synthesized compounds was performed using IR, 1H-NMR and 13C-NMR spectroscopy. Biological evaluations focused on antioxidant properties, including reducing power, free radical scavenging capacity, and metal chelating activity. The antioxidant effects of the compounds were found to be generally weak. Antimicrobial activity tests, performed against Bacillus cereus, Klebsiella pneumoniae, Staphylococcus aureus, Serratia marcescens, and Candida albicans using the agar well diffusion method, revealed that some compounds exhibited strong antimicrobial properties. This study emphasizes the significant biological potential of triazole derivatives, suggesting that their bioactivity can be further enhanced through functional group modifications.

This study is among the pioneering investigations evaluating the embryonic effects of triazol-5-one derivatives administered in ovo to broiler embryos. The synthesized compound, 1-(morpholin-4-yl-methyl)-3-(p-chlorobenzyl)-4-(4-hydroxybenzylideneamino)-4,5-dihydro-1H-1,2,4-triazol-5-one, was examined for its in vitro biological properties and in ovo embryonic safety. The compound is hypothesized to influence embryonic viability in a manner consistent with its structural and biological characteristics. Structural confirmation was achieved through FT-IR, ¹H-NMR, and ¹³C-NMR analyses. In vitro assays showed weak reducing and radical-scavenging capacity but high, stable metal-chelating activity, alongside strong antimicrobial effects. For the in ovo trial, 120 fertilized Ross-308 eggs were assigned to three groups (Control, Dimethyl sulfoxide (DMSO), Experimental; n = 40). On day 17, 0.5 mL of solution was injected into the amniotic cavity, and embryos were monitored until 510 h. Hatchability was 87.5% in the Control group, 80% in the DMSO group, and 0% in the Experimental group. No live chicks hatched in the experimental group, indicating complete embryonic lethality. All embryo losses occurred after injection during incubation, and Levene’s test followed by one-way ANOVA (p = 0.385) confirmed no initial weight differences, indicating a compound-specific effect. The compound’s embryotoxicity may result from strong metal chelation, low antioxidant capacity, oxidative stress, mitochondrial dysfunction, and membrane disruption. These findings provide a basis for defining safe dose ranges, optimizing injection parameters, and assessing the in ovo applicability of related triazole compounds.

Bu çalışmada, 3-hidroksibenzaldehit ile 2,5-diklorobenzensulfonil klorürün trietilamin ortamındaki reaksiyonundan yeni 3-formilfenil 2,5-diklorobenzensulfonat (2) bileşiği sentezlenmiştir. Sentezlenen benzaldehit türevi bileşik (2) ile literatürde kayıtlı dokuz adet 3-alkil/aril-4-amino-4,5-dihidro-1H-1,2,4-triazol-5-on (1a-1i) bileşikleri reaksiyona sokulmuştur. Reaksiyon sonucunda dokuz adet yeni 3-[(3-alkil/aril-4,5-dihidro-1H-1,2,4-triazol-5-on-4-il)-azometin]-fenil 2,5-diklorobenzensulfonat (3a-3i) bileşikleri sentezlenmiştir. Sentezlenen yeni Schiff bazı bileşiklerin (3a-3i) yapıları IR, 1H-NMR, 13C-NMR spektroskopik yöntemler ile karakterizasyonu yapılmıştır. Yeni bileşiklerin (3a-3i) hem antibakteriyel hem de antioksidan özelliklerine bakılarak biyolojik özellikleri incelenmiştir. Antibakteriyel özellikleri Agar kuyucuk difüzyon metodu ile incelenmiş ve gözlemlemeler sonucunda 3a-3d, 3h ve 3i bileşiklerinin iyi antibakteriyel aktiviteye sahip olduğu belirlenmiştir. Antioksidan özellikleri Blois, Dinis, Oyaizu metotları ile incelenmiş ve sentezlenen yeni bileşiklerin (3a-3i) standart olarak kullanılan α-tokoferole oldukça yakın düzeyde metal şelat aktivitesine sahip olduğu gözlemlenmiştir. Ayrıca, yeni Schiff bazı bileşiklerinin (3a-3i) dört farklı susuz çözücüde (DMF, izopropil alkol, aseton ve tert-butil alkol) tetrabutilamonyum hidroksit (TBAH) ile titre edilerek asidik özelliklerine bakılmış, yarı nötralizasyon potansiyelleri ve bunlara karşılık gelen pKa değerleri belirlenmiştir.

In this study, a total of nine new 2-[(3-alkyl/aryl-4,5-dihydro-1H-1,2,4-triazol-5-one-4-yl)azomethine]phenyl 2,5-dichlorobenzenesulfonates (4a-i) were synthesized through the reactions of 2-formylphenyl 2,5-dichlorobenzenesulfonate (3) with 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (2a-i). The compounds 4a, 4e, 4g and 4h were successfully synthesized with yields exceeding 90%. Compounds 4a-i were elucidated using 1H, 13C NMR and IR spectroscopic methods. The spectroscopic data were compared with the literature, and the results were found to be consistent. The antioxidant effects of compounds 4a–i were investigated using three different methods, and it was found that compounds 4a-i showed metal chelation activity close to that of α-tocopherol, which was used as the standard. Additionally, the antimicrobial properties of the compounds 4a–i were evaluated using the agar well diffusion method against six different bacterial strains. The antimicrobial properties of the new compounds (4a-i) were compared with those of standard antibiotics such as neomycin, streptomycin, and ampicillin. It was observed that compound 4a exhibited better antimicrobial activity than neomycin and streptomycin, and comparable activity to ampicillin.