From BACE1 inhibitor to multifunctionality of tryptoline and tryptamine triazole derivatives for Alzheimer's disease.

ABSTRACT: Efforts to discover new drugs for Alzheimer's disease emphasizing multiple targets was conducted seeking to inhibit amyloid oligomer formation and to prevent radical formation. The tryptoline and tryptamine cores of BACE1 inhibitors previously identified by virtual screening were modified in silico for additional modes of action. These core structures were readily linked to different side chains using 1,2,3-triazole rings as bridges by copper catalyzed azide-alkyne cycloaddition reactions. Three compounds among the sixteen designed compounds exerted multifunctional activities including β-secretase inhibitory action, anti-amyloid aggregation, metal chelating and antioxidant effects at micromolar levels. The neuroprotective effects of the multifunctional compounds 6h, 12c and 12h on Aβ₁₋₄₂ i

SUBMITTER: Jiaranaikulwanitch J 

PROVIDER: S-EPMC3618987 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature