Abstract: Two oxoisoaporphine-melatonin hybrids(compound 2a and 2b) have been designed, synthesized and tested for their ability to inhibit acetylcholinesterase, butyrylcholinesterase, acetylcholinesterase-induced β-amyloid(Aβ) aggregation. Their inhibitory mechanism and antioxidant properties were also studied. The synthetic compounds(2a and 2b) exhibited moderate AChE inhibitory activity with IC50 values in the micromolar range in most cases. Non-competitive binding mode was found for these derivatives. Moreover, the compounds(2a and 2b) exhibit high acetylcholinesterase-induced Aβ antiaggregating activity with inhibitory potencies ranging from 79.3% to 84.7%, and significant antioxidant properties with peroxyl radical absorbance capacities ranging from 1.1- to 1.5-fold the value of trolox.

Key words: Oxoisoaporphine derivatives, melatonin, cholinesterase, antioxidant, A&, beta, antiaggregating