The chemical chaperone 4-phenylbutyric acid (4-PBA) has potential as an agent for the treatment of neurodegenerative diseases. However, the requirement of high concentrations warrants chemical optimization for clinical use. In this study, novel naphthalene derivatives with a greater chemical chaperone activity than 4-PBA were synthesized with analogy to the benzene ring. All novel compounds showed chemical chaperone activity, and 2 and 5 possessed high activity. In subsequent experiments, the protective effects of the compounds were examined in Parkinson's disease model cells, and low toxicity of 9 and 11 was related to amphiphilic substitution with naphthalene.
Keywords: 4-Phenylbutyric acid (4-PBA); Chemical chaperone; Endoplasmic reticulum (ER) stress; Naphthalene; Parkinson’s disease (PD).
Copyright © 2015 Elsevier Ltd. All rights reserved.