Yazar "Tarikogullari, Ayse H." seçeneğine göre listele

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    Design, Synthesis, and In Silico Analyses of Nitroimidazole Derivatives Targeting Cholinesterases
    (Wiley-V C H Verlag Gmbh, 2025) Biyik, Busra; Tarikogullari, Ayse H.; Alagoz, Mehmet Abdullah; Demir, Yeliz; Gulcin, Ilhami; Burmaoglu, Serdar; Algul, Oztekin
    The increasing incidence of diseases and the constraints of current treatments require expedited drug development. Drug repositioning presents an effective approach for discovering new therapeutic applications for drugs already in clinical use. This study examines the efficacy of metronidazole and secnidazole, which are presently utilized as antiprotozoal agents, in the treatment of Alzheimer's disease via ester modifications. The secondary alcohol group in nitroimidazole structures underwent esterification with acetyl, pivaloyl, cyclopropyl, and cyclohexyl carbonyl chlorides. The compounds exhibited significant inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), with Ki values between 52.40 +/- 6.99 nM and 240.80 +/- 45.56 nM for AChE and 77.82 +/- 18.01 nM and 323.70 +/- 56.21 nM for BChE. Molecular docking studies demonstrated significant interactions of the most active compounds (MNZ 8 and MNZ 4) with essential residues, including Trp84 and Phe330 in AChE, as well as Trp82 and active-site water molecules in BChE. These findings corroborate their inhibitory potential, notwithstanding initial positional alterations observed during simulations. The synthesized compounds' absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties were also assessed in silico. All compounds demonstrated drug-like properties and did not exhibit undesirable toxic effects. The findings indicate that repositioned derivatives of metronidazole and secnidazole may serve as promising lead compounds for the development of cholinesterase inhibitors aimed at treating Alzheimer's disease.
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    Exploring enzyme inhibition profiles of novel halogenated chalcone derivatives on some metabolic enzymes: Synthesis, characterization and molecular modeling studies
    (Elsevier Sci Ltd, 2022) Anil, Derya Aktas; Polat, M. Fatih; Saglamtas, Ruya; Tarikogullari, Ayse H.; Alagoz, M. Abdullah; Gulcin, Ilhami; Algul, Oztekin
    Enzyme inhibition is a very active area of research in drug design and development. Chalcone derivatives have a broad enzyme inhibitory activity and function as potential molecules in the development of new drugs. In this study, the synthesized novel halogenated chalcones with bromobenzyl and methoxyphenyl moieties were evaluated toward the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes and human erythrocyte carbonic anhydrase I (hCA I), and II (hCA II) isoenzymes. They showed highly potent inhibition ability toward AChE with Ki values of 1.83 +/- 0.21-11.19 +/- 0.96 nM and BChE with Ki values of 3.35 +/- 0.91-26.70 +/- 4.26 nM; hCA I with Ki values of 29.41 & PLUSMN; 3.14-57.63 & PLUSMN; 4.95 nM, and hCA II with Ki values of 24.00 & PLUSMN; 5.39-54.74 & PLUSMN; 1.65 nM. Among the tested enzyme inhibitions, compounds 14 and 13 were the most active compounds against AChE and BChE. Docking studies were performed to the most active compounds against AChE, BChE, hCA I and hCA II to propose a binding mode in the active site and molecular dynamics simulations were studied to check the molecular interactions and the stability of the ligands in the active site. The results may contribute to the development of new drugs particularly to treat some global disorders including Alzheimer's disease (AD), glaucoma, and diabetes.