Sürdürülebilir Kalkınma Amaçları

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• MakaleAçık Erişim2027/r/gumushane/13442
  Design, Synthesis, and X-ray Characterization of Benzohydrazide Derivatives as Cholinesterase Inhibitors for the Treatment of Alzheimer’s Disease: An Experimental and Computational Approach to Biological Activity

  Topal, Fevzi; Ünver, Hakan; Topal, Meryem; Çevik, Ulviye Acar; Kırboğa, Kevser Kübra; Işık, Mesut; Beydemir, Şükrü

  In this study, a series of new benzohydrazide derivatives (1a-i) were synthesized, and characterized as potential cholinesterase inhibitors for use in the treatment of Alzheimer’s disease (AD). The inhibitory activities of the synthesized compounds against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes were evaluated using in vitro and in silico methods. IC50 values for AChE inhibition ranged from 29.50 to 46.21 nM, with compound 1c exhibiting the highest inhibitory potential at an IC50 of 29.50 nM. For the BChE enzyme, the strongest effect was observed with compound 1d at an IC50 of 55 nM. The synthesized derivatives exhibited higher inhibitory potential compared to the reference tacrine (IC50: 58.73 nM for AChE and 187.30 nM for BChE) against cholinesterase enzymes through both competitive and non-competitive inhibition mechanisms. Molecular docking (ΔG: -10.67 to -9.95 kcal/mol for AChE; -9.80 to -8.69 kcal/mol for BChE) and 100 ns molecular dynamics simulations supported the binding affinities and indicated the dynamic stability of the enzyme-inhibitor complexes, in agreement with the experimental inhibition data. In silico ADMET profiling indicated favourable drug-likeness and high predicted gastrointestinal absorption and blood-brain barrier permeability (TPSA 41.46-61.69 A2), and structural alert screening returned no PAINS matches. The findings suggest that these derivatives may serve as promising lead compounds for further investigation as potential cholinesterase inhibitors relevant to AD, pending experimental cytotoxicity evaluation.

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  İncele
• MakaleYalnız künye2026/r/gumushane/13777
  Synthesis, characterization, and thermal-magnetic evaluation of novel triazine-derived polyamides and their metal complexes

  Çanakçı, Dilek; Sarıbıyık, Oğuz Yunus

  In this work, novel triazine-containing polyamide derivatives possessing thermal stability and magnetic properties were synthesized. The synthesis process involves two steps: first, the chlorination of adipic acid and succinic acid using thionyl chloride; and second, the amidation of triazine. As a result of these procedures, two different triazine-containing polyamides were synthesized. The synthesized polyamides formed complexes with Ag, Cu, and Zn ions to enhance their thermal stability and magnetic properties.The structures of the synthesized polyamides were elucidated primarily by FTIR analysis, focusing on distinctive bands corresponding to the carbonyl group. The molecular structures of the polyamides were confirmed using 1H NMR and 13C NMR spectroscopy. Scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDX) was employed to obtain information on the morphology and elemental composition of the samples. In addition, X-ray diffraction (XRD) analysis was performed to characterize the crystal structures, unit cell parameters, and orientations of the solid-state metal complexes. The thermal stability of both the polyamides and their metal complexes was investigated using thermogravimetric analysis (TGA). The magnetization of the synthesized compounds was measured as a function of temperature under zero-field-cooled (ZFC) and field-cooled (FC) conditions using a physical property measurement system (PPMS).

  İncele
• MakaleYalnız künye2026/r/gumushane/13497
  Novel 1,2,4-triazole-based n-mannich derivatives: Synthesis, spectroscopic characterization, cytotoxic, antimicrobial, and enzyme inhibitory activities, and in silico studies

  Yılmaz, Yonca; Medetalibeyoğlu, Hilal; Kapancık, Serkan; Tüzün, Burak; Lukšič, Miha; Aslan, Rukiye; Topal, Fevzi; Kocyigit, Umit M.; Yüksek, Haydar; Harmankaya, Ahmet

  A series of novel 1,2,4-triazole-based Mannich bases was designed, synthesized, and evaluated for biological and theoretical properties. Schiff base intermediates (C1–6) were prepared by condensing 4-benzoxy-3-methoxybenzaldehyde with various 3-substituted-4-amino-4,5-dihydro-1H-1,2,4-triazole-5-ones. Mannich reactions with formaldehyde and 2,6-dimethylmorpholine produced six target compounds (D1–6). Structures were confirmed using spectroscopic techniques. Following structural confirmation, the compounds showed significant cytotoxicity against HT-29 and MCF-7 cancer cell lines in MTT assays. Enzyme inhibition studies demonstrated activity against glucose-6-phosphate dehydrogenase (G6PDH) and lactate dehydrogenase (LDH), indicating potential relevance to cancer metabolism. Moderate acetylcholinesterase inhibition was observed, with IC50 values from 56.81 to 182.40 µM. Antimicrobial testing showed that D1, D3, D4, and D5 were active against selected microbial strains, while D2 and D6 were inactive. Density functional theory (DFT) calculations, molecular docking, ADME/T predictions, and molecular mechanics simulations were conducted to complement the experimental findings. These computational analyses indicated favorable binding interactions and pharmacological profiles.In summary, the newly synthesized triazole-based Mannich derivatives represent promising candidates for further pharmacological investigation.

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  İncele
• MakaleYalnız künye2024/r/gumushane/12669
  Three novel 1,2,3-triazole-fused compounds: Syntheses, structural and spectroscopic characterizations with molecular modeling

  Ejder, Esengül; Onur, Sultan; Yıldırım, Arzu Özek; Yıldırım, Muhammet Hakkı; Tümer, Ferhan

  In this study, we report syntheses, structural and spectroscopic characterizations, and molecular modeling of three novel triazole fused compounds: 4-((4-methoxyphenoxy)methyl)-1-(4-methoxyphenyl)-1H-1,2,3-triazole, 1-(4-isopropylphenyl)-4-((4-methoxyphenoxy)methyl)-1H-1,2,3-triazole, and 1-(4-fluorophenyl)-4-((4-methoxyphenoxy)methyl)-1H-1,2,3-triazole. Their molecular structures and intermolecular interactions were elucidated using single-crystal X-ray crystallography. The compounds crystallize in the P-1 and P21/c space groups with weak C−H∙∙∙N and C-H∙∙∙O interactions. Hirshfeld surface analyses revealed the complex network of intermolecular interactions, determining that in all three compounds, an average of 13 % of the packing interactions were due to hydrogen bonds, and an average of 25 % were due to C-H···π interactions. Since the compounds differ from each other by only one substituent (methoxy, isopropyl, and fluorine) in their phenyl ring, their experimental infrared spectra were clarified by comparing them with the calculated ones. NMR spectroscopy was employed to examine the behavior of the compounds in solution. Conformational scans revealed that the energy differences between conformers are low, indicating potential conformations in which compounds could exist in solution. Nonlinear optical properties were calculated to evaluate the potential of the compounds for optical applications, particularly emphasizing the significantly larger values seen for two compounds compared to a reference compound. Finally, molecular electrostatic potential maps were generated to visualize the charge distribution and potential electrophilic and nucleophilic attack regions.

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