title: Synthesis of long-chain fatty acid derivatives as a novel anti-Alzheimer's agent.
abstract: In order to develop new drugs for Alzheimer's disease, we prepared 17 fatty acid derivatives with different chain lengths and different numbers and positions of double bonds by using Wittig reaction and stereospecific hydrogenation of triple bonds as key reactions. Among them, (4Z,15Z)-octadecadienoic acid (10) and (23Z,34Z)-heptatriacontadienoic acid (16) showed the most potent neurite outgrowth activities on Aβ(25-35)-treated rat cortical neurons, which activities were comparable to that of a positive control, NGF. Both fatty acids 10 and 16 possess two (Z)-double bonds at the n-3 and n-14 positions, which might be important for the neurite outgrowth activity.
authors.affiliation: Division of Natural Products Chemistry, Institute of Natural Medicine, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
authors.forename: Yu-ichiro
authors.initials: Y
authors.lastname: Yamakawa
authors.affiliation: Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuya
authors.affiliation: Graduate School of Science and Technology for Research, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan; Graduate School of Innovative Life Science, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan. Electronic address: toyooka@eng.u-toyama.ac.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Toyooka
authors.affiliation: Division of Division of Neuromedical Science, Institute of Natural Medicine, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Tohda
authors.affiliation: Frontier Research Core for Life Sciences, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
authors.forename: Suresh
authors.initials: S
authors.lastname: Awale
authors.affiliation: Research Promotion Office, Joint Usage/Research Center for Science-Based Natural Medicine, Institute of Natural Medicine, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Division of Natural Products Chemistry, Institute of Natural Medicine, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan.
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Kadota
authors.affiliation: Division of Natural Products Chemistry, Institute of Natural Medicine, University of Toyama, Sugitani 2630, Toyama 930-0194, Japan. Electronic address: tezuka@inm.u-toyama.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tezuka
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D002478:Cells, Cultured; D005227:Fatty Acids / Q000138:chemical synthesis* / Q000627:therapeutic use*; D016501:Neurites / Q000187:drug effects* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats
chemical_list: D005227:Fatty Acids
keywords: Anti-Alzheimer’s agent; Long-chain fatty acid; Neurite outgrowth activity; Synthesis