title: Oleic acid and linoleic acid from Tenebrio molitor larvae inhibit BACE1 activity in vitro: molecular docking studies.
abstract: In our ongoing research to find therapeutic compounds for Alzheimer's disease (AD) from natural resources, the inhibitory activity of the BACE1 enzyme by Tenebrio molitor larvae and its major compounds were evaluated. The T. molitor larvae extract and its fractions exhibited strong BACE1 suppression. The major components of hexane fraction possessing both high yield and strong BACE1 inhibition were determined by thin layer chromatography, gas chromatography, and nuclear magnetic resonance analysis. A remarkable composition of unsaturated long chain fatty acids, including oleic acid and linoleic acid, were identified. Oleic acid, in particular, noncompetitively attenuated BACE1 activity with a half-maximal inhibitory concentration (IC₅₀) value of 61.31 μM and Ki value of 34.3 μM. Furthermore, the fatty acids were stably interacted with BACE1 at different allosteric sites of the enzyme bound with the OH of CYS319 and the NH₃ of TYR320 for oleic acid and with the C=O group of GLN304 for linoleic acid. Here, we first revealed novel pharmacophore features of oleic acids and linoleic acid to BACE1 by in silico docking studies. The present findings would clearly suggest potential guidelines for designing novel BACE1 selective inhibitors.
authors.affiliation: 1 Department of Food Science and Nutrition, Dong-A University , Saha-gu, Busan, Korea.
authors.forename: Kumju
authors.initials: K
authors.lastname: Youn
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Yun
authors.forename: Jinhyuk
authors.initials: J
authors.lastname: Lee
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Jae-Sam
authors.initials: JS
authors.lastname: Hwang
authors.forename: Woo-Sik
authors.initials: WS
authors.lastname: Jeong
authors.forename: Mira
authors.initials: M
authors.lastname: Jun
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D007814:Larva / Q000737:chemistry* / Q000254:growth & development; D019787:Linoleic Acid / Q000737:chemistry*; D062105:Molecular Docking Simulation; D019301:Oleic Acid / Q000737:chemistry*; D013712:Tenebrio / Q000737:chemistry* / Q000254:growth & development
chemical_list: D004791:Enzyme Inhibitors; D019301:Oleic Acid; D019787:Linoleic Acid; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human