Phenolic Compounds: Investigating Their Anti-Carbonic Anhydrase, Anti-Cholinesterase, Anticancer, Anticholinergic, and Antiepileptic Properties Through Molecular Docking, MM-GBSA, and Dynamics Analyses

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dc.authoridTUZUN, BURAK/0000-0002-0420-2043
dc.contributor.authorAkkus, Musa
dc.contributor.authorKirici, Mahinur
dc.contributor.authorPoustforoosh, Alireza
dc.contributor.authorErdogan, Mehmet Kadir
dc.contributor.authorGundogdu, Ramazan
dc.contributor.authorTuzun, Burak
dc.contributor.authorTaslimi, Parham
dc.date.accessioned2025-05-04T16:47:23Z
dc.date.available2025-05-04T16:47:23Z
dc.date.issued2025
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstractPhenolic compounds are a new class of Carbonic Anhydrase inhibitors (CAIs). Despite numerous advancements in treatment approaches, cancer continues to be a growing health problem worldwide. In our study, we tested the effects of 4-hydroxy-3-methoxyacetophenone (1), doxycycline hydrochloride (2), 5,7-dichloro-8-hydroxyquinoline (3), methyl 3,4,5-trihydroxybenzoate (4), 2-hydroxy-4-methylacetophenone (5), 6-hydroxy-4-methylcoumarin (6), and 2,5-dihydroxyacetophenone (7) on Achetylcholynesterase (AChE), Butrycholynesterase (BChE), and Human Carbonic anhydrase I (hCA I) enzymes. The U2OS human osteosarcoma cell line was used to determine the anticancer potential of these phenolic compounds. The effects of the compounds on proliferation and colony formation were analyzed using the Neutral Red Uptake (NRU) assay and the clonogenic assay. The Ki values of arachidonoyl dopamine, 2,4,6-trihydroxybenzaldehyde, and 3,4-dihydroxy-5-methoxybenzoic acid were 203.80, 1170.00, and 910.00 mM, respectively, for hCA I, and 75.25, 354.00, and 1510.00 mM, respectively, for Human Carbonic anhydrase II (hCA II). Additionally, IC50 values from in vivo studies were found to range from 173.25 to 1360.00 mM for CA I and CA II, respectively, using CO2-hydratase activity methods. The NRU assay results revealed that the compounds had a dose-dependent cytotoxic effect on U2OS cells. The IC50 values of the compounds in U2OS osteosarcoma cells were determined to be > 100, 93.7, 81.4, 26.9, > 100, 53.1, and > 100 mu M, respectively. Notably, methyl 3,4,5-trihydroxybenzoate (4), the compound with the lowest IC50 value, significantly suppressed colony formation at 5 and 10 mu M concentrations. These results demonstrated that the phenolic compounds used in in vivo studies could inhibit approximately 30% of the CO2-hydratase activity of the total CA enzyme of rat erythrocytes. Furthermore, the anticancer potential of the tested compounds suggests that these molecules could pave the way for the development of new approaches in cancer treatment. The activities of the seven molecules studied were compared against AChE (PDB ID: 4M0E), BChE (PDB ID: 5NN0), hCA I (PDB ID: 2CAB), and E3 ubiquitin-protein ligase (PDB ID: 4HG7) proteins. The binding free energy of the molecule with the highest docking score is computed using MM/GBSA techniques. Finally, molecular dynamics simulations were performed between 6-hydroxy-4-methylcoumarin and the 4M0E protein over a 0-200 ns interval.
dc.description.sponsorshipSivas Cumhuriyet niversitesi [RGD-020]; Scientific Research Project Fund of Sivas Cumhuriyet University (CUBAP)
dc.description.sponsorshipThis work was supported by the Scientific Research Project Fund of Sivas Cumhuriyet University (CUBAP) under the project number RGD-020.
dc.identifier.doi10.1007/s11814-025-00401-8
dc.identifier.endpage1168
dc.identifier.issn0256-1115
dc.identifier.issn1975-7220
dc.identifier.issue5
dc.identifier.scopus2-s2.0-85217639608
dc.identifier.scopusqualityQ2
dc.identifier.startpage1149
dc.identifier.urihttps://doi.org/10.1007/s11814-025-00401-8
dc.identifier.urihttps://hdl.handle.net/20.500.12418/35592
dc.identifier.volume42
dc.identifier.wosWOS:001416601900001
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherKorean Institute Chemical Engineers
dc.relation.ispartofKorean Journal of Chemical Engineering
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.snmzKA_WOS_20250504
dc.subjectPhenolic substance
dc.subjectEnzyme inhibition
dc.subjectMolecular docking
dc.subjectAnticancer
dc.subjectMolecular dynamic
dc.titlePhenolic Compounds: Investigating Their Anti-Carbonic Anhydrase, Anti-Cholinesterase, Anticancer, Anticholinergic, and Antiepileptic Properties Through Molecular Docking, MM-GBSA, and Dynamics Analyses
dc.typeArticle

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