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    Boron Containing Curcumin-Like Compound as an Acetylcholinesterase Inhibitor and Anticancer Agent: Synthesis, Biological Evaluation, and Computational Insights
    (Humana Press Inc, 2025) Comert Onder, Ferah; Ural, Kadircan; Onder, Alper; Ozpolat, Bulent; Ay, Mehmet
    Alzheimer's disease (AD) and cancer are significant global health challenges that highlight the need for the development of new therapeutics. Targeting biological mechanisms involved in both AD and cancer could be an effective treatment strategy for developing novel inhibitors. In this study, we investigated the effect of a newly synthesized boron containing curcumin-like compound as a potential acetylcholinesterase (AChE) inhibitor along with its cytotoxic effects on breast and colorectal cancer cell lines. Compound A exhibited a potent AChE inhibitory activity (IC50 = 22.89 +/- 2.32 nM), demonstrating that it was more effective than the known inhibitors donepezil (IC50 = 28.32 +/- 3.27 nM) and tacrine. Compound A showed a moderate cytotoxic activity on MCF-7 and BT20 cells with the IC50 values 40.70 +/- 2.31 mu M and 41.71 +/- 4.51 mu M, respectively. Throughout molecular dynamics (MD) simulations, the RMSD value of the protein was calculated as 1.56 +/- 0.20 & Aring; and 1.65 +/- 0.19 & Aring; for the complexes of compound A and curcumin, respectively. The interactions with specific amino acid residues such as Tyr124, Tyr337, and Trp86 for AChE, and Trp82, His438, and Tyr332 for BChE were obtained. Additionally, MM/GBSA calculations demonstrated that Compound A had the highest binding free energies (-88.89 +/- 8.34 kcal/mol for AChE and -73.25 +/- 8.83 kcal/mol for BChE) compared to curcumin (-67.87 +/- 5.48 kcal/mol for AChE and -51.68 +/- 5.28 kcal/mol for BChE) and tacrine (-56.67 +/- 2.22 kcal/mol for BChE) were calculated. Overall, these findings suggest that Compound A is a promising agent with its potent AChE inhibitory activity and anticancer potential, making it a valuable candidate for further research in neurodegenerative diseases and cancer therapy.
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    Design, synthesis, characterization, in silico studies, and in vitro anticancer evaluation of novel 7-methoxyquinolone-substituted triazole hybrids
    (Taylor & Francis Ltd, 2025) Allito, Lemiye; Comert Onder, Ferah; Demirel, Ramazan; Onder, Alper; Ozden, Ozkan; Erdogan, Musa
    AimsThe quinolone scaffold is a crucial member of the heterocyclic compound family in modern medicinal chemistry, exhibiting a broad range of biological activities. Since 4-quinolones are known to interact with significant drug targets, and due to the remarkable pharmacological properties of 1,2,3-triazole compounds, a molecular hybridization approach was used to design novel 7-methoxyquinolone-substituted triazole hybrid conjugates (QN1-QN11).Materials and methodsThese hybrid compounds were evaluated to determine their anticancer activities in various breast and colon cancer cell lines, including BT20, MDA-MB-231, MCF7, and HT29. In addition, the apoptotic-like morphological changes in aggressive MDA-MB-231 cells were observed following treatment with the compounds for 48 hours. In silico studies, including molecular docking, molecular dynamics (MD) simulation, and MM/GBSA calculations, were carried out for the synthesized compounds against important cancer drug targets.ResultsThe highly cytotoxic agents QN10 and QN7 were identified with IC50 values of 4.49 +/- 0.68 mu M and 19.05 +/- 1.58 mu M in BT20 and HT29 cell lines, respectively. In addition, the morphologically changes were observed on MDA-MB-231 cells.ConclusionsThese findings show that the synthesized click products are highly cytotoxic agents in cancer cell lines and may be considered as potential candidates for enzyme inhibition.
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    New and potential boron-containing compounds for treatment of Alzheimer's disease and cancers
    (Taylor & Francis Ltd, 2025) Comert Onder, Ferah; Ural, Kadircan; Onder, Alper; Ozpolat, Bulent; Ay, Mehmet
    AimIn this study, new boron-containing carbamate compounds were synthesized and evaluated as potential acetylcholinesterase (AChE) inhibitors by in vitro and in silico analyses.Materials & methodsThe structures were characterized by spectroscopic analysis including 1H NMR, 13C NMR, 11B NMR, and MS. The purities of the compounds were determined by HPLC analysis. In vitro and in silico analyses were performed.ResultsBased on our findings, compounds (1-4) demonstrated more potent AChE inhibitory activity compared to tacrine, which is an FDA-approved AChE inhibitor. Compound 4 had the highest inhibitory activity with an IC50 of 37.87 +/- 0.96 nM and was more effective than tacrine (74.23 +/- 0.83 nM). Compounds 1, 2, and 3, respectively, showed 1.78-, 1.73-, and 1.58-fold more potent enzyme inhibition activity compared to tacrine. The strong interactions with critical residues in the binding pocket of AChE were identified between protein and the compounds. Furthermore, compound 4 exerted an antiproliferative activity against various human cancer cell lines (32.91 +/- 4.92 mu M in HT29 and 42.38 +/- 2.73 mu M in MCF-7).ConclusionOur study indicates the discovery of new boron-containing AChE inhibitors as potential candidates for the treatment of Alzheimer's disease and cancer.
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    Recent developments in natural bioactive peptides: Anticancer potential and structure–activity relationships
    (Elsevier B.V., 2022) Comert Onder, Ferah; Ay, Mehmet
    Most of the drugs used in medicine have been obtained from natural products or their synthetic derivatives. Bioactive peptides are an important group of natural product sources isolated from marine organisms, plants, animals, and microorganisms. Bioactive peptides have been investigated to promote health because of their high tissue affinity, specificity, and efficiency. Therefore, they possess a key role in cancer, including early diagnosis, prognostic predictors, and treatment. Anticancer effects of peptides have been widely investigated and shown to have many advantages as peptide-based drugs. Many naturally occurring peptides such as plitidepsin, dolastatin 10, didemnin B, and kahalalide F are used in clinical trials for the treatment of various cancers. The structure-activity relationship of these peptides can contribute to the design and development of peptide-based drugs. The aim of this chapter is to review the recent developments in bioactive peptides and their role in cancer therapy. © 2022 Elsevier B.V.
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    Repurposing of FDA-Approved Drugs as Acetylcholinesterase Inhibitors for Alzheimer's Disease: A Combined In Silico and In Vitro Evaluation and Structure-Activity Relationship
    (Wiley-V C H Verlag Gmbh, 2025) Sikik, Merve; Comert Onder, Ferah
    Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by cognitive decline and decreased cholinergic activity that affects millions of individuals worldwide. Herein, in vitro acetylcholinesterase (AChE) inhibitory potentials of FDA-approved drugs identified by computational approaches, including structure-based virtual screening, molecular dynamics (MD) simulations, and molecular mechanics-generalized Born surface area (MM/GBSA), were carried out. The top docking poses of the selected drugs (Trazodone, Frovatriptan, Eletriptan, Bupropion, Rivaroxaban, Sotalol, and Indapamide) were analyzed during 200 ns MD simulations. The average root-mean-square deviation (RMSD) values along with standard deviation were calculated for all complexes between approximately 1.90 +/- 0.37 and 1.59 +/- 0.21 & Aring;. The average RMSD values of AChE-Trazodone and AChE-Rivaroxaban, respectively, were found to be 1.69 +/- 0.19 and 1.74 +/- 0.30 & Aring;. On the basis of in vitro findings, Trazodone (12.61 +/- 0.52 nM) showed 2.11-fold more inhibitory activity than donepezil (DNP). In vitro AChE activity of Rivaroxaban (26.82 +/- 0.51 nM) was found to be similar to DNP (26.67 +/- 0.56 nM). Frovatriptan, Eletriptan, Bupropion, Sotalol, and Indapamide had 1.84-, 1.70-, 1.67-, 1.29-, and 1.23-fold higher activity than tacrine. This study highlights the potency of the studied FDA-approved drugs to inhibit AChE for the treatment of AD through in silico and in vitro studies.