Resumo:
Pt
|
Texto:
Pt
|
PDF:
Pt
This study aimed to synthesize novel compounds as more effective carbonic anhydrase II inhibitors. For this purpose, 2-(3-methoxy-4-(prop-2-yn-1-yloxy)phenyl)-4,5-diphenyl-1H-imidazole (3) was reacted with 3-methoxy-4-(prop-2-yn-1-yloxy)benzaldehyde through the glyoxal reaction to produce a series of imidazole-based 1,2,3-triazoles 5a-f. The synthesized compounds were structurally confirmed using IR, 1H, and 13C NMR techniques. To evaluate their potential as inhibitors of carbonic anhydrase II enzyme, the synthesized compounds were tested via in vitro enzyme inhibition assay. Among the derivatives, compounds 5f and 5a exhibited the most promising inhibitory potential, with IC50 values of 0.025 ± 0.001 and 0.032 ± 0.003 µM, respectively. Both 5a and 5f derivatives have comparable inhibitory potential but 5f was found to be more potent than 5a: Molecular docking analysis revealed that compounds 5a and 5f displayed excellent binding scores of -8.0 and -8.4 kcal mol-1, respectively. The results were further validated by MD simulations. The RMSD analysis revealed the average values of 3.20 Å for the ligand-protein complex, 1.38 Å for the apoprotein, and 7.15 Å for the ligand molecule. Based on the chemical stability and biological importance, the compound 5f was identified as potential lead candidates for the development of more effective carbonic anhydrase II inhibitors. purpose 23methoxy4prop2yn1yloxyphenyl4,5diphenyl1Himidazole 23methoxy4prop2yn1yloxyphenyl45diphenyl1Himidazole methoxypropynyloxyphenyldiphenylHimidazole 2 3 methoxy 4 prop yn 1 yloxy phenyl 4,5 diphenyl 1H imidazole 5 H (3 3methoxy4prop2yn1yloxybenzaldehyde methoxypropynyloxybenzaldehyde benzaldehyde imidazolebased based 1,2,3triazoles 123triazoles triazoles 1,2,3 5af. 5af af f. f 5a-f IR C techniques assay IC IC5 0025 0 025 0.02 0001 001 0.00 0032 032 0.03 0003 003 µM respectively 8.0 80 8 -8. 8.4 84 mol1, mol1 mol 1, mol-1 simulations 320 20 3.2 ligandprotein protein complex 138 38 1.3 apoprotein 715 7 15 7.1 molecule importance 23methoxy4prop2yn1yloxyphenyl4 5diphenyl1Himidazole yloxyphenyl Himidazole 45 4, ( yloxybenzaldehyde 3triazoles 123 1,2, 002 02 0.0 000 00 03 8. -8 mol- 32 3. 13 1. 71 7. methoxypropynyloxyphenyl 23methoxy4prop2yn1yloxyphenyl diphenylHimidazole 12 1,2 0. -