Tacrine, Trolox and Tryptoline as Lead Compounds for the Design and Synthesis of Multi-target Agents for Alzheimer's Disease Therapy.

ABSTRACT: The versatile biological activities of tacrine, trolox and β-carboline derivatives make them promising lead structures for the development of multifunctional Alzheimer's disease (AD) agents. Based on the topology of the active site of cholinesterases and other target proteins involved in the pathogenesis of AD, we have designed and synthesized tacrine-trolox and tacrine-tryptoline hybrids with various linker chain lengths. The hybrids containing the trolox moiety (8a-8d) showed moderate to high TcAChE inhibition (IC₅₀: 17.37 - 2200 nM), eqBuChE inhibition (IC₅₀: 3.16 - 128.82 nM) and free radical scavenging activities (IC₅₀: 11.48 - 49.23 µM). The hybrids with longer linker chain lengths in general showed better ChE inhibitory activity. As exp

SUBMITTER: Teponnou GAK 

PROVIDER: S-EPMC5418947 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature