New and potential boron-containing compounds for treatment of Alzheimer's disease and cancers

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 ¹H NMR, ¹³C NMR, ¹¹B 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 IC₅₀ 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 µM in HT29 and 42.38 ± 2.73 µM 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.