A Novel Donepezil-Caffeic Acid Hybrid: Synthesis, Biological Evaluation, and Molecular Docking Studies

被引：0

作者：

Kilicaslan, Derya ^{[1
]}

Kurt, Akif Hakan ^{[2
]}

Kose, Muhammet ^{[3
]}

Cesme, Mustafa ^{[3
]}

Gungor, Ozge ^{[3
]}

Oztabag, Cansu Kara ^{[4
]}

Doganer, Adem ^{[5
]}

机构：

[1] Kahramanmaras Sutcu Imam Univ, Afsin Vocat Sch, Dept Chem & Chem Proc Technol, Kahramanmaras, Turkiye

[2] Bolu Abant Izzet Baysal Univ, Fac Med, Dept Pharmacol, Bolu, Turkiye

[3] Kahramanmaras Sutcu Imam Univ, Fac Art & Sci, Dept Chem, Kahramanmaras, Turkiye

[4] Bolu Abant Izzet Baysal Univ, Inst Hlth Sci, Dept Interdisciplinary Neurosci, Bolu, Turkiye

[5] Kahramanmaras Sutcu Imam Univ, Fac Med, Dept Biostat & Med Informat, Kahramanmaras, Turkiye

来源：

BIOCHEMISTRY-MOSCOW | 2023年 / 88卷 / 01期

关键词：

donepezil; caffeic acid; hybrid molecule; acetylcholinesterase; molecular docking; protective effect; TARGET-DIRECTED LIGANDS; ALZHEIMERS-DISEASE; ACETYLCHOLINESTERASE INHIBITORS; DESIGN; DERIVATIVES; BINDING; AGENTS; THERAPY; POTENT;

D O I：

10.1134/S0006297923010054

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A novel donepezil-caffeic acid (DP-CA) hybrid molecule was designed, synthesis, and investigated by molecular modeling. Its biological activity and protective effect were investigated by the IR spectroscopy, H-1 and C-13 NMR spectroscopy, and mass spectrometry. DP-CA was highly active against acetylcholine esterase and inhibited it at the micromolar concentrations. Fluorescence and UV-Vis spectroscopy studies showed strong binding of DP-CA to DNA. Moreover, DP-CA exhibited protective effects against H2O2-induced toxicity in U-118 MG glioblastoma cells. Finally, molecular docking showed a high affinity of DP-CA in all concentrations, and the active 4EY7 site exhibited essential residues with polar and apolar contacts. Taken together, these findings indicate that DP-CA could be a prospective multifunctional agent for the treatment of neurodegenerative diseases.

引用

页码：50 / 63

页数：14

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