Wang_2026_Molecules_31_595

A new series of tacrine-coumarin hybrids (compounds 15a-18b) linked by 1,2,3-triazole had been designed and synthesized as multifunctional ligands for the treatment of Alzheimer's disease (AD). The inhibitory effects of the synthesized compounds on AChE and BuChE, their ability to inhibit Abeta aggregation, and their MAO inhibitory activities were evaluated. In vitro studies showed that some of the hybrids (compounds 17a-18b) exhibited significant abilities to inhibit both AChE and BuChE, self-induced Abeta aggregation, and MAO-B. In particular, compound 17d showed a well-balanced inhibitory profile against AChE and BuChE (IC(50) = 0.080 +/- 0.007 microM for AChE, IC(50) = 0.044 +/- 0.004 microM for BuChE), self-induced Abeta aggregation (58.4% +/- 2.1% at 20 microM), and MAO-B (IC(50) = 0.18 +/- 0.01 microM), suggesting that 17d might be an excellent multifunctional agent for AD treatment. In addition, compounds 15a and 15b were identified as selective inhibitors of BuChE at micromolar concentrations.