Design, Synthesis, and Biological Activity of Novel 1,3,5-Triazine–1,2,4-Triazine Hybrids as Cholinesterase Inhibitors

Abstract Fourteen 1,3,5-triazine–1,2,4-triazine hybrids were designed and synthesized. Their structures were confirmed by IR, NMR, and high-resolution mass spectra, as well as by single crystal X-ray diffraction. The cholinesterase inhibitory activities of the hybrids were assayed by Ellman’s method. Five of the fourteen hybrids inhibited acetylcholinesterase by more than 50% at a concentration of 50 μM. Only two hybrids inhibited butyrylcholinesterase by more than 50% at a concentration of 50 μM. Compound 5c possessed the best acetyl­cholinesterase and butyrylcholinesterase inhibitory activities with IC 50 of 6.80±0.14 μM and 1.91±0.12 μM, respectively. Molecular docking showed that compound 5c interacted with both catalytic active site and peripheral anionic site of acetylcholinesterase.