title: Inhibition of β-Secretase Activity by Monoterpenes, Sesquiterpenes, and C13Norisoprenoids.
abstract: Inhibition of β-secretase (BACE1) is currently regarded as the leading treatment strategy for Alzheimer's disease. In the present study, we aimed to screen the in vitro inhibitory activity of 80 types of aroma compounds (monoterpenes, sesquiterpenes, and C13norisoprenoids), including plant-based types, at a 200-μM concentration against a recombinant human BACE1. The results showed that the most potent inhibitor of BACE1 was geranyl acetone followed by (+)-camphor, (-)-fenchone, (+)-fenchone, and (-)-camphor with the half-maximal inhibitory concentration (IC50) values of 51.9 ± 3.9, 95.9 ± 11.0, 106.3 ± 14.9, 117.0 ± 18.6, and 134.1 ± 16.4 μM, respectively. Furthermore, the mechanism of inhibition of BACE1 by geranyl acetone was analyzed using Dixon kinetics plus Cornish-Bowden plots, which revealed mixed-type mode. Therefore aroma compounds may be used as potential lead molecules for designing anti-BACE1 agents.
authors.affiliation: Joint Research Center, Kindai University (Former name: Kinki University).
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Marumoto
authors.affiliation: Department of Materials Science, Wakayama National College of Technology.
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Okuno
authors.affiliation: Graduate School of Materials Science, Nara Institute of Science and Technology.|Graduate School of Science, Osaka City University.|Department of Applied Chemistry, Kindai University (Former name: Kinki University).
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Miyazawa
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D001892:Camphanes; D002164:Camphor / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D058990:Molecular Targeted Therapy; D039821:Monoterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D009636:Norbornanes / Q000494:pharmacology / Q000627:therapeutic use; D045792:Norisoprenoids / Q000494:pharmacology*; D008517:Phytotherapy; D011994:Recombinant Proteins; D012717:Sesquiterpenes / Q000494:pharmacology*; D013729:Terpenes / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D001892:Camphanes; D004791:Enzyme Inhibitors; D039821:Monoterpenes; D009636:Norbornanes; D045792:Norisoprenoids; D011994:Recombinant Proteins; D012717:Sesquiterpenes; D013729:Terpenes; C027327:fenchone; D002164:Camphor; C009884:geranylacetone; D053829:Amyloid Precursor Protein Secretases
keywords: C13 norisoprenoid; monoterpene; sesquiterpene; terpenoids; β-Secretase (BACE1) inhibitory activity