Yazar "Aslan, Osman Nuri" seçeneğine göre listele

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    Design, synthesis, and inhibition of ?-glucosidase by novel L-phenylalanine-derived hydrazones: Kinetic, molecular docking, and dynamics studies
    (Elsevier Science Inc, 2025) Kalay, Erbay; Adem, Sevki; Demir, Yeliz; Aslan, Osman Nuri; Sahin, Engin; Eyupoglu, Volkan; Comakli, Veysel
    In this paper, a series of novel hydrazones derived from L-phenyl alanine were synthesized in four steps and employed to inhibit alpha-glucosidase through kinetic studies, molecular docking, and molecular dynamics analyses. Among the synthesized compounds, 8, 15, and 16 exhibited the strongest inhibitory effects, with IC50 values of 31.08 mu M, 24.15 mu M, and 19.47 mu M, respectively, surpassing the standard inhibitor acarbose (79.63 mu M). Molecular docking studies revealed robust interactions, with compound 16 achieving the highest MolDock score of -176.316. Molecular dynamics simulations were conducted to evaluate the binding affinity of compound 16 to the isomaltase enzyme from Saccharomyces cerevisiae (3A4A). The most favorable docking pose was subjected to further analysis through MD simulations under dynamic conditions. The MMGBSA analysis of the simulation cluster indicated a strong binding affinity of approximately -43.06 kcal/mol, highlighting the compound's potential for modulating alpha-glucosidase activity. These results underscore the potential of bromine and hydroxylsubstituted hydrazones to modulate isomaltase activity, with therapeutic implications for hyperglycemia and obesity management.
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    Rhodanine-Sulfonate hybrids targeting aldose reductase: Synthesis, in vitro inhibition, molecular docking, and cytotoxicity studies
    (Springer, 2025) Kalay, Erbay; Demir, Yeliz; Turkes, Cuneyt; Aslan, Osman Nuri; Pezik, Esra; Sahin, Engin
    Aldose reductase (ALR2), a key enzyme in the polyol pathway, plays a significant role in the onset and progression of diabetic complications, rendering it a critical pharmacological target. In this study, a novel series of twenty-four sulfonate ester-functionalized rhodanine derivatives (compounds 1-24) were rationally designed, synthesized via Knoevenagel condensation, and comprehensively evaluated for their inhibitory activity against ALR2. Spectroscopic and spectrometric methods confirmed the structural integrity of the synthesized compounds. In vitro enzyme inhibition assays revealed that all compounds acted as competitive inhibitors, with several analogues, particularly compounds 6 and 8, exhibiting stronger ALR2 inhibition (Ki = 0.43 mu M and 0.48 mu M, respectively) than the reference drug epalrestat (Ki = 0.98 mu M). Structure-activity relationship (SAR) analysis highlighted the critical influence of para-substituted electron-donating (e.g., methyl) and electron-withdrawing (e.g., nitro, halogen) groups on binding potency. Molecular docking of the most potent inhibitor (compound 6) demonstrated a stable binding pose supported by key interactions, including hydrogen bonding with His110 and pi-pi stacking with Phe122. In silico ADME profiling confirmed favorable drug-likeness properties for all derivatives. Cytotoxicity studies on L929, A549, and RG-2 cell lines revealed that most compounds were less toxic than the reference drug at lower concentrations, with compound 8 showing a promising cytotoxic profile. These findings position rhodanine-sulfonate hybrids as promising scaffolds for the development of next-generation ALR2 inhibitors for the treatment of diabetic complications.