Yazar "Oh, Jong Min" seçeneğine göre listele

Listeleniyor 1 - 4 / 4
  • Küçük Resim Yok
    Öğe
    Design, Synthesis, and Biological Evaluation of Pyridazinones Containing the (2-Fluorophenyl) Piperazine Moiety as Selective MAO-B Inhibitors
    (Mdpi, 2020) Cecen, Muhammed; Oh, Jong Min; Ozdemir, Zeynep; Buyuktuncel, Saliha Ebru; Uysal, Mehtap; Abdelgawad, Mohamed A.; Musa, Arafa
    Twelve pyridazinones (T1-T12) containing the (2-fluorophenyl) piperazine moiety were designed, synthesized, and evaluated for monoamine oxidase (MAO) -A and -B inhibitory activities. T6 was found to be the most potent MAO-B inhibitor with an IC50 value of 0.013 mu M, followed by T3 (IC50 = 0.039 mu M). Inhibitory potency for MAO-B was more enhanced by meta bromo substitution (T6) than by para bromo substitution (T7). For para substitution, inhibitory potencies for MAO-B were as follows: -Cl (T3) > -N(CH3)(2) (T12) > -OCH3 (T9) > Br (T7) > F (T5) > -CH3 (T11) > -H (T1). T6 and T3 efficiently inhibited MAO-A with IC50 values of 1.57 and 4.19 mu M and had the highest selectivity indices (SIs) for MAO-B (120.8 and 107.4, respectively). T3 and T6 were found to be reversible and competitive inhibitors of MAO-B with K-i values of 0.014 and 0.0071, respectively. Moreover, T6 was less toxic to healthy fibroblast cells (L929) than T3. Molecular docking simulations with MAO binding sites returned higher docking scores for T6 and T3 with MAO-B than with MAO-A. These results suggest that T3 and T6 are selective, reversible, and competitive inhibitors of MAO-B and should be considered lead candidates for the treatment of neurodegenerative disorders like Alzheimer's disease.
  • Küçük Resim Yok
    Öğe
    Development of a Novel Class of Pyridazinone Derivatives as Selective MAO-B Inhibitors
    (Mdpi, 2022) Alagoz, Mehmet Abdullah; Oh, Jong Min; Zenni, Yaren Nur; Ozdemir, Zeynep; Abdelgawad, Mohamed A.; Naguib, Ibrahim A.; Ghoneim, Mohammed M.
    Sixteen compounds (TR1-TR16) were synthesized and evaluated for their inhibitory activities against monoamine oxidase A and B (MAOs). Most of the derivatives showed potent and highly selective MAO-B inhibition. Compound TR16 was the most potent inhibitor against MAO-B with an IC50 value of 0.17 mu M, followed by TR2 (IC50 = 0.27 mu M). TR2 and TR16 selectivity index (SI) values for MAO-B versus MAO-A were 84.96 and higher than 235.29, respectively. Compared to the basic structures, the para-chloro substituent in TR2 and TR16 increased the inhibitory activity of MAO-B. TR2 and TR16 were reversible MAO-B inhibitors that were competitive, with K-i values of 0.230 +/- 0.004 and 0.149 +/- 0.016 mu M, respectively. The PAMPA method indicated that compounds TR2 and TR16 had the tendency to traverse the blood-brain barrier. Docking investigations revealed that lead compounds were beneficial for MAO-B inhibition via association with key as well as selective E84 or Y326 residues, but not for MAO-A inhibition via interaction primarily driven by hydrophobic contacts. In conclusion, TR2 and TR16 are therapeutic prospects for the management of multiple neurodegenerative diseases.
  • Küçük Resim Yok
    Öğe
    Inhibition of Cholinesterases by Benzothiazolone Derivatives
    (Mdpi, 2022) Alagoz, Mehmet Abdullah; Kim, Seong-Min; Oh, Jong Min; Arslan, Gulnur; Ozdemir, Zeynep; Sari, Suat; Ozcelik, Azime Berna
    Thirteen benzothiazolone derivatives (M1-M13) were synthesized and evaluated for their inhibitory activity against cholinesterases (ChEs) and monoamine oxidases (MAOs). All the compounds inhibited ChEs more effectively than MAOs. In addition, most of the compounds showed higher inhibitory activities against butyrylcholinesterase (BChE) than acetylcholinesterase (AChE). Compound M13 most potently inhibited BChE with an IC50 value of 1.21 mu M, followed by M2 (IC50 = 1.38 mu M). Compound M2 had a higher selectivity index (SI) value for BChE over AChE (28.99) than M13 (4.16). The 6-methoxy indole group of M13 was expected to have a greater effect on BChE inhibitory activity than the other groups. Kinetics and reversibility tests showed that M13 was a reversible noncompetitive BChE inhibitor with a K-i value of 1.14 +/- 0.21 mu M. In a docking simulation, M13 is predicted to form a hydrogen bond with the backbone carbonyl group of Ser287 of BChE through its methoxy indole moiety and pi-pi interactions between its benzothiazolone group and the side chain of Trp82 with the five-membered pyrrole ring and with the six-membered benzene ring. From these results, it is suggested that M13 is a BChE inhibitor and a potential candidate agent for the treatment of Alzheimer's disease.
  • Küçük Resim Yok
    Öğe
    Inhibition of Monoamine Oxidases by Pyridazinobenzylpiperidine Derivatives
    (Mdpi, 2024) Oh, Jong Min; Zenni, Yaren Nur; Ozdemir, Zeynep; Kumar, Sunil; Kilic, Semanur; Akdag, Mevlut; Ozcelik, Azime Berna
    Monoamine oxidase inhibitors (MAOIs) have been crucial in the search for anti-neurodegenerative medications and continued to be a vital source of molecular and mechanistic diversity. Therefore, the search for selective MAOIs is one of the main areas of current drug development. To increase the effectiveness and safety of treating Parkinson's disease, new scaffolds for reversible MAO-B inhibitors are being developed. A total of 24 pyridazinobenzylpiperidine derivatives were synthesized and evaluated for MAO. Most of the compounds showed a higher inhibition of MAO-B than of MAO-A. Compound S5 most potently inhibited MAO-B with an IC50 value of 0.203 mu M, followed by S16 (IC50 = 0.979 mu M). In contrast, all compounds showed weak MAO-A inhibition. Among them, S15 most potently inhibited MAO-A with an IC50 value of 3.691 mu M, followed by S5 (IC50 = 3.857 mu M). Compound S5 had the highest selectivity index (SI) value of 19.04 for MAO-B compared with MAO-A. Compound S5 (3-Cl) showed greater MAO-B inhibition than the other derivatives with substituents of -Cl > -OCH3 > -F > -CN > -CH3 > -Br at the 3-position. However, the 2- and 4-position showed low MAO-B inhibition, except S16 (2-CN). In addition, compounds containing two or more substituents exhibited low MAO-B inhibition. In the kinetic study, the K-i values of S5 and S16 for MAO-B were 0.155 +/- 0.050 and 0.721 +/- 0.074 mu M, respectively, with competitive reversible-type inhibition. Additionally, in the PAMPA, both lead compounds demonstrated blood-brain barrier penetration. Furthermore, stability was demonstrated by the 2V5Z-S5 complex by pi-pi stacking with Tyr398 and Tyr326. These results suggest that S5 and S16 are potent, reversible, selective MAO-B inhibitors that can be used as potential agents for the treatment of neurological disorders.