ABSTRACT
In this study, a series of novel ferulic and caffeic acid dimers was designed and synthesised, and their multifunctional properties against Alzheimer's disease (AD) were evaluated. Results showed that our multifunctional strategy was great supported by enhancing the inhibition of Aß1-42 self-induced aggregation. Moreover, 7b also had potent protective effects against glutamate-induced cell death without significant cell toxicity in mouse hippocampal neuronal HT22 cells and 10c effectively scavenged diphenylpicrylhydrazyl free radicals. Collectively, these data strongly encourage further optimisation of 7b as a new hit to develop multifunctional agents for the treatment of AD.
Subject(s)
Alzheimer Disease/drug therapy , Caffeic Acids/chemical synthesis , Caffeic Acids/therapeutic use , Coumaric Acids/chemical synthesis , Coumaric Acids/therapeutic use , Amyloid beta-Peptides/antagonists & inhibitors , Animals , Antioxidants/pharmacology , Biphenyl Compounds/chemistry , Cell Death/drug effects , Cell Line , Free Radical Scavengers/chemistry , Free Radical Scavengers/pharmacology , Glutamic Acid/toxicity , Humans , Mice , Neurons/drug effects , Peptide Fragments/antagonists & inhibitors , Picrates/chemistryABSTRACT
The total synthesis of cyclomarin C was accomplished through a convergent strategy from a tetrapeptide fragment and a tripeptide one. The developed methods to prepare the needed noncoded amino acids, the proper protection of peptide fragments, and identification of the optimum macrocylization site can be applied to further synthetic studies on other members of cyclomarins. [structure: see text]
