title: Inhibition of Acyl-CoA: cholesterol acyltransferase (ACAT), overexpression of cholesterol transporter gene, and protection of amyloid β (Aβ) oligomers-induced neuronal cell death by tricyclic pyrone molecules.
abstract: A major effort in Alzheimer's disease therapeutic development has targeted Aβ and downstream events. We have synthesized a small library of tricyclic pyrone compounds. Their protective action in MC65 cells and inhibition of ACAT along with the upregulation of cholesterol transporter gene were investigated. Five active compounds exhibited potencies in the nanomolar ranges. The multiple effects of the compounds on Aβ and cellular cholesterol pathways could be potential mechanisms underlying the protective effects in vivo.
authors.affiliation: Department of Chemistry, 213 CBC Building, Kansas State University, Manhattan, Kansas 66503, USA.
authors.forename: Laxman
authors.initials: L
authors.lastname: Pokhrel
authors.forename: Izumi
authors.initials: I
authors.lastname: Maezawa
authors.forename: Thi D T
authors.initials: TD
authors.lastname: Nguyen
authors.forename: Kyeong-Ok
authors.initials: KO
authors.lastname: Chang
authors.forename: Lee-Way
authors.initials: LW
authors.lastname: Jin
authors.forename: Duy H
authors.initials: DH
authors.lastname: Hua
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000101:Acetyl-CoA C-Acetyltransferase / Q000037:antagonists & inhibitors*; D016229:Amyloid beta-Peptides / Q000502:physiology*; D016923:Cell Death; D002460:Cell Line; D015870:Gene Expression; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016229:Amyloid beta-Peptides; D006575:Heterocyclic Compounds, 3-Ring; D011753:Pyrones; D000101:Acetyl-CoA C-Acetyltransferase