Phenolic Compounds: Investigating Their Anti-Carbonic Anhydrase, Anti-Cholinesterase, Anticancer, Anticholinergic, and Antiepileptic Properties Through Molecular Docking, MM-GBSA, and Dynamics Analyses DOI Creative Commons
Musa Tozlu, Mahinur Kırıcı, Alireza Poustforoosh

и другие.

Korean Journal of Chemical Engineering, Год журнала: 2025, Номер unknown

Опубликована: Фев. 8, 2025

Abstract Phenolic compounds are a new class of Carbonic Anhydrase inhibitors (CAIs). Despite numerous advancements in treatment approaches, cancer continues to be growing health problem worldwide. In our study, we tested the effects 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), Human anhydrase I (hCA I) enzymes. The U2OS human osteosarcoma cell line was used determine anticancer potential these phenolic compounds. proliferation colony formation were analyzed using Neutral Red Uptake (NRU) assay clonogenic assay. K i values arachidonoyl dopamine, 2,4,6-trihydroxybenzaldehyde, 3,4-dihydroxy-5-methoxybenzoic acid 203.80, 1170.00, 910.00 mM, respectively, for hCA I, 75.25, 354.00, 1510.00 II II). Additionally, IC 50 from vivo studies found range 173.25 1360.00 mM CA II, CO 2 -hydratase activity methods. NRU results revealed that had dose-dependent cytotoxic effect cells. cells determined > 100, 93.7, 81.4, 26.9, 53.1, 100 µM, respectively. Notably, compound with lowest value, significantly suppressed at 5 10 µM concentrations. These demonstrated could inhibit approximately 30% CO2-hydratase total enzyme rat erythrocytes. Furthermore, suggests molecules pave way development approaches treatment. activities seven studied compared against AChE (PDB ID: 4M0E), BChE 5NN0), 2CAB), E3 ubiquitin-protein ligase 4HG7) proteins. binding free energy molecule highest docking score is computed MM/GBSA techniques. Finally, molecular dynamics simulations performed between 4M0E protein over 0–200 ns interval. Graphical abstract

Язык: Английский

Phenolic Compounds: Investigating Their Anti-Carbonic Anhydrase, Anti-Cholinesterase, Anticancer, Anticholinergic, and Antiepileptic Properties Through Molecular Docking, MM-GBSA, and Dynamics Analyses DOI Creative Commons
Musa Tozlu, Mahinur Kırıcı, Alireza Poustforoosh

и другие.

Korean Journal of Chemical Engineering, Год журнала: 2025, Номер unknown

Опубликована: Фев. 8, 2025

Abstract Phenolic compounds are a new class of Carbonic Anhydrase inhibitors (CAIs). Despite numerous advancements in treatment approaches, cancer continues to be growing health problem worldwide. In our study, we tested the effects 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), Human anhydrase I (hCA I) enzymes. The U2OS human osteosarcoma cell line was used determine anticancer potential these phenolic compounds. proliferation colony formation were analyzed using Neutral Red Uptake (NRU) assay clonogenic assay. K i values arachidonoyl dopamine, 2,4,6-trihydroxybenzaldehyde, 3,4-dihydroxy-5-methoxybenzoic acid 203.80, 1170.00, 910.00 mM, respectively, for hCA I, 75.25, 354.00, 1510.00 II II). Additionally, IC 50 from vivo studies found range 173.25 1360.00 mM CA II, CO 2 -hydratase activity methods. NRU results revealed that had dose-dependent cytotoxic effect cells. cells determined > 100, 93.7, 81.4, 26.9, 53.1, 100 µM, respectively. Notably, compound with lowest value, significantly suppressed at 5 10 µM concentrations. These demonstrated could inhibit approximately 30% CO2-hydratase total enzyme rat erythrocytes. Furthermore, suggests molecules pave way development approaches treatment. activities seven studied compared against AChE (PDB ID: 4M0E), BChE 5NN0), 2CAB), E3 ubiquitin-protein ligase 4HG7) proteins. binding free energy molecule highest docking score is computed MM/GBSA techniques. Finally, molecular dynamics simulations performed between 4M0E protein over 0–200 ns interval. Graphical abstract

Язык: Английский

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