Comert_2025_Future.Med.Chem__1

AIM: In this study, new boron-containing carbamate compounds were synthesized and evaluated as potential acetylcholinesterase (AChE) inhibitors by in vitro and in silico analyses. MATERIALS & METHODS: The structures were characterized by spectroscopic analysis including (1)H NMR, (13)C NMR, (11)B NMR, and MS. The purities of the compounds were determined by HPLC analysis. In vitro and in silico analyses were performed. RESULTS: Based on our findings, compounds (1-4) demonstrated more potent AChE inhibitory activity compared to tacrine, which is an FDA-approved AChE inhibitor. Compound 4 had the highest inhibitory activity with an IC(50) of 37.87 +/- 0.96 nM and was more effective than tacrine (74.23 +/- 0.83 nM). Compounds 1, 2, and 3, respectively, showed 1.78-, 1.73-, and 1.58-fold more potent enzyme inhibition activity compared to tacrine. The strong interactions with critical residues in the binding pocket of AChE were identified between protein and the compounds. Furthermore, compound 4 exerted an antiproliferative activity against various human cancer cell lines (32.91 +/- 4.92 microM in HT29 and 42.38 +/- 2.73 microM in MCF-7). CONCLUSION: Our study indicates the discovery of new boron-containing AChE inhibitors as potential candidates for the treatment of Alzheimer's disease and cancer.