title: Synthesis and SAR Studies of Neuritogenic Gentiside Derivatives.
abstract: Tetradecyl 2,3-dihydroxybenzoate (ABG-001) has been designed and synthesised as a lead compound to treat Alzheimer's disease, based on structure-activity relationships of gentisides. In this paper, the alkyl chain and ester linkage group of ABG-001 were modified. Consequently, several series of novel gentiside derivatives were designed and synthesised, and their neuritogenic activity was evaluated in PC12 cells. Among all the tested compounds, S-dodecyl 2,3-dihydroxybenzothioate (15d, named as ABG-199) was the most potent; the compound induced significant neurite outgrowth at 0.1 µM, which was comparable to that of nerve growth factor at the optimal concentration of 40 ng/mL and ABG-001 at 1 µM. A brief study on the mechanism of action of ABG-199 revealed that extracellular signal-regulated kinase phosphorylation was involved in ABG-199-induced neurite outgrowth in PC12 cells.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang University.
authors.forename: Guangfa
authors.initials: G
authors.lastname: Wang
authors.forename: Linglin
authors.initials: L
authors.lastname: Bian
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Wang
authors.forename: Lijuan
authors.initials: L
authors.lastname: Gao
authors.forename: Kaiyue
authors.initials: K
authors.lastname: Sun
authors.forename: Lan
authors.initials: L
authors.lastname: Xiang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Qi
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D062385:Hydroxybenzoates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D016501:Neurites / Q000187:drug effects* / Q000473:pathology; D016716:PC12 Cells; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D062385:Hydroxybenzoates; C571109:tetradecyl-2,3-dihydroxybenzoate