| Title: |
Assessing the Potential of 1,2,3-Triazole-Dihydropyrimidinone Hybrids Against Cholinesterases: In Silico, In Vitro, and In Vivo Studies. |
| Authors: |
Gastalho, Carlos M., Sena, Ana M., López, Óscar, Fernández-Bolaños, José G., García-Sosa, Alfonso T., Pereira, Florbela, Antunes, Célia M., Costa, Ana R., Burke, Anthony J., Carreiro, Elisabete P. |
| Source: |
International Journal of Molecular Sciences; Oct2024, Vol. 25 Issue 20, p11153, 20p |
| Subject Terms: |
CHOLINESTERASES, MOLECULAR docking, GALANTHAMINE, ARTEMIA, ANTIOXIDANTS |
| Abstract: |
Combining the pharmacological properties of the 1,2,3-triazole and dihydropyrimidinone classes of compounds, two small families of mono- and di(1,2,3-triazole)-dihydropyrimidinone hybrids, A and B, were previously synthesized. The main objective of this work was to investigate the potential anti-Alzheimer effects of these hybrids. The inhibitory activities of cholinesterases (AChE and BuChE), antioxidant activity, and the inhibitory mechanism through in silico (molecular docking) and in solution (STD-NMR) experiments were evaluated. The 1,2,3-triazole-dihydropyrimidinone hybrids (A and B) showed moderate in vitro inhibitory activity on eqBuChE (IC50 values between 1 and 58.4 μM). The best inhibitor was the hybrid B4, featuring two 1,2,3-triazole cores, which exhibited stronger inhibition than galantamine, with an IC50 of 1 ± 0.1 μM for eqBuChE, through a mixed inhibition mechanism. Among the hybrids A, the most promising inhibitor was A1, exhibiting an IC50 of 12 ± 2 µM, similar to that of galantamine. Molecular docking and STD-NMR experiments revealed the key binding interactions of these promising inhibitors with BuChE. Hybrids A and B did not display Artemia salina toxicity below 100 μM. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
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