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

Laxman Pokhrel, Izumi Maezawa, Thi D T Nguyen, Kyeong Ok Chang, Lee-Way Jin, Duy H. Hua

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

A major effort in Alzheimers 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.

Original languageEnglish (US)
Pages (from-to)8969-8973
Number of pages5
JournalJournal of Medicinal Chemistry
Volume55
Issue number20
DOIs
StatePublished - Oct 25 2012

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Pyrones
Sterol O-Acyltransferase
Amyloid
Cell Death
Cholesterol
Genes
Alzheimer Disease
Up-Regulation
Inhibition (Psychology)
Therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

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abstract = "A major effort in Alzheimers 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.",
author = "Laxman Pokhrel and Izumi Maezawa and Nguyen, {Thi D T} and Chang, {Kyeong Ok} and Lee-Way Jin and Hua, {Duy H.}",
year = "2012",
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language = "English (US)",
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T2 - Cholesterol acyltransferase (ACAT), overexpression of cholesterol transporter gene, and protection of amyloid β (Aβ) oligomers-induced neuronal cell death by tricyclic pyrone molecules

AU - Pokhrel, Laxman

AU - Maezawa, Izumi

AU - Nguyen, Thi D T

AU - Chang, Kyeong Ok

AU - Jin, Lee-Way

AU - Hua, Duy H.

PY - 2012/10/25

Y1 - 2012/10/25

N2 - A major effort in Alzheimers 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.

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