Optimizing kinase and PARP inhibitor combinations through machine learning and in silico approaches for targeted brain cancer therapy

Molecular Diversity, Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

Язык: Английский

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Design, synthesis, in silico studies and antiproliferative evaluation of some novel hybrids of pyrimidine-morpholine

Frontiers in Chemistry, Год журнала: 2025, Номер 13

Опубликована: Фев. 28, 2025

Introduction Cancer is a complex group of diseases characterized by the uncontrolled growth and spread abnormal cells in body. These can invade nearby tissues organs, or they may metastasize to other parts body through bloodstream lymphatic system. Methods In this study, eight novel pyrimidine-morpholine hybrides ( 2a-2h ) were designed synthesized based on molecular hybridization approach identify potent cytotoxic agents. Spectroscopic methods, including infrared spectroscopy (IR), proton carbon nuclear magnetic resonance 1 HNMR & 13 CNMR), mass spectrometry, employed confirm structures compounds. The effects derivatives evaluated against cancerous cell lines, MCF-7 SW480, using MTT assay. Results discussion It was demonstrated that all had appropriate potential with IC 50 range 5.12–117.04 μM. Compound 2g identified as most compound, exhibiting values 5.10 ± 2.12 μM 19.60 1.13 toward SW480 respectively. Cell cycle analysis showed could induces phase arrest breast cancer cells. apoptosis assay induction line. biological activity compounds confirmed docking studies. DFT for 2h conducted at B3LYP/6-31+G** level theory. concluded both thermodynamically kinetically more stable than . Moreover, interpretation ADME (Absorption, Distribution, Metabolism, Excretion) indicates these new series possess acceptable prognostic physicochemical properties. serve promising candidates further investigation anticancer

Язык: Английский

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Spiroindoline quinazolinedione derivatives as inhibitors of P-glycoprotein: potential agents for overcoming multidrug resistance in cancer therapy

Molecular Diversity, Год журнала: 2025, Номер unknown

Опубликована: Март 19, 2025

Язык: Английский

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

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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In-silico Study of an Inhibitor of S-Adenosyl-L-Homocysteine Hydrolase (SAHH) of Naegleria fowleri using Molecular Docking, Density Functional Theory (DFT), and Molecular Dynamics (MD) Simulation

Molecular Biotechnology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 13, 2025

Язык: Английский

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Identification of potential inhibitors of the E2 protein of Eastern equine encephalitis virus (EEEV) using molecular docking, density functional theory, and molecular dynamics simulations: an in silico approach

Chemical Papers, Год журнала: 2025, Номер unknown

Опубликована: Март 14, 2025

Язык: Английский

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Exploring Antiproliferative Potential, In Silico Docking, and Molecular Dynamics of Pyrimidine-Morpholine Hybrid Molecules

Current Pharmaceutical Analysis, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Язык: Английский

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