Bazı Yeni 1,2,4-Triazol-3-Tiyo-N-Sübstitüeamit Türevlerinin Sentezi ve Alzheimer Hastalığı Üzerine Etkilerinin Araştırılması
Özet
In the current study, forty new compounds that have 5-naphthyl-1,2,4-triazole and 5-naphthyloxymethyl-1,2,4-triazole rings moiety linked to the benzothiazole, thiazole, and phenyl scaffolds via amid chain, were designed and synthesized as selective BChE inhibitors. The structures of the synthesized compounds were elucidated by IR, 1H NMR, 13C NMR, ESI-MS and HRMS spectral methods. The inhibitory effects and selectivity of the compounds on acetylcholinesterase and butrylcholinesterase enzymes were determined using Ellman method. The inhibitory activity results revealed that most of these compounds exhibited significant inhibitor potency on BChE while all synthesized compounds showed no significant activity on AChE. The cytotoxicity effect against SH-SY5Y cells and antioxidant capacity of the most active derivatives were investigated. In addition, enzyme kinetic studies were performed to determine the inhibition types of 2-[(4-allyl-5-((naphthalen-1-yloxy)methyl)-4H-1,2,4-triazol-3-yl)thio]-N-(thiazol-2-yl)acetamide and 2-[(4-methyl-5-((naphthalen-2-yloxy)methyl)-4H-1,2,4-triazol-3-yl)thio]-N-(thiazol-2-yl)acetamide, which are the derivatives with the highest BChE inhibitory activity, and their effects on the inhibition of amyloid β aggregation and neuroprotective effects against H2O2 and Aβ1-42-induced cytotoxicity on SH-SY5Y cells were evaluated.Protein-ligand interactions in the active sites of AChE and BChE enzymes of the selected compounds were investigated.
