title: Evaluation of synthetic naphthalene derivatives as novel chemical chaperones that mimic 4-phenylbutyric acid.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomicho, Choshi, Chiba 288-0025, Japan. Electronic address: smimori@cis.ac.jp.
authors.forename: Seisuke
authors.initials: S
authors.lastname: Mimori
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomicho, Choshi, Chiba 288-0025, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Koshikawa
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomicho, Choshi, Chiba 288-0025, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Mashima
authors.affiliation: Faculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Mitsunaga
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, Chiba 288-0025, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawada
authors.affiliation: Department of Biochemistry, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kaneko
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, Chiba 288-0025, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Okuma
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Kurume University, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nomura
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomicho, Choshi, Chiba 288-0025, Japan.
authors.forename: Yasuoki
authors.initials: Y
authors.lastname: Murakami
authors.affiliation: Department of Clinical Medicine, Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomicho, Choshi, Chiba 288-0025, Japan.
authors.forename: Tetsuto
authors.initials: T
authors.lastname: Kanzaki
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomicho, Choshi, Chiba 288-0025, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamana
mesh_terms: D045744:Cell Line, Tumor; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006801:Humans; D018832:Molecular Chaperones / Q000737:chemistry*; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry*; D010300:Parkinson Disease / Q000188:drug therapy; D010654:Phenylbutyrates / Q000737:chemistry*; D015398:Signal Transduction
chemical_list: D018832:Molecular Chaperones; D009281:Naphthalenes; D010654:Phenylbutyrates; C075773:4-phenylbutyric acid
keywords: 4-Phenylbutyric acid (4-PBA); Chemical chaperone; Endoplasmic reticulum (ER) stress; Naphthalene; Parkinson’s disease (PD)