Tamaddon-Abibigloo_2025_J.Mol.Struct_1324_140717

In this study a new series of isatin-1,3,5-triazine-benzylamine hybrids (6a-k) were designed, synthesized and evaluated for in vitro anti-Alzheimer's disease(AD) properties. These molecules were tested for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibition and biometal chelation effect. Results revealed these molecules to be very potent AChE inhibitors with IC50 values in the range of 0.8636.30 nM. BChE inhibition potencies were also good and IC50 values for active compounds were from 0.66 to 3.88 microM. Molecule 6c had the highest activity against both enzymes and further studies showed that it kinetically inhibited AChE and BChE with non-competitive and competitive mechanisms, respectively. This compound could effectively inhibit amyloid beta self/Cu2+ induced aggregation in 10microM. These compounds could significantly chelate to Cu2+ as an important biometal involved in AD andin silico simulations demonstrated that these molecules had key interactions with both ChE enzymes. It was concluded that these compounds had high potency to be used in future evaluations as anti-AD lead compounds.