Design, synthesis and biological evaluation of Schiff ’s base derivatives as multifunctional agents for the treatment of Alzheimer’s disease

AbstractA series of Schiff ’s base derivatives was rationally designed, synthesized, and evaluated as multi-function agents for the treatment of Alzheimer’s disease (AD). The results revealed that compound3b was a novel multifunctional agent. It acted as a highly selective monoamine oxidase-B inhibitor (IC50 = 8.4 nM), which was explained by the docking study. Compound3b also was an antioxidant agent (2.3 eq) and could significantly inhibit self-induced Aβ1-42 aggregation (31.8%). Meanwhile, compound3b was a selective metal chelator and could inhibit Cu2+-induced Aβ1-42 aggregation (62.3%). Furthermore, compound3b presented good neuroprotective effects on H2O2-induced PC12 cell injury. More importantly, compound demonstrated good blood brain barrier permeability and druglike properties. Therefore, compound3b, a promising multi-targeted active molecule, offers an attractive starting point for further study in the drug-discovery process against AD.
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research