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

doi:10.1021/jm3012189

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

Pathology and Laboratory Medicine

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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 language	English (US)
Pages (from-to)	8969-8973
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	55
Issue number	20
DOIs	https://doi.org/10.1021/jm3012189
State	Published - Oct 25 2012

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/jm3012189

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Pokhrel, L., Maezawa, I., Nguyen, T. D. T., Chang, K. O., Jin, L-W., & Hua, D. H. (2012). 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. Journal of Medicinal Chemistry, 55(20), 8969-8973. https://doi.org/10.1021/jm3012189

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

In: Journal of Medicinal Chemistry, Vol. 55, No. 20, 25.10.2012, p. 8969-8973.

Research output: Contribution to journal › Article › peer-review

Pokhrel, L, Maezawa, I, Nguyen, TDT, Chang, KO, Jin, L-W & Hua, DH 2012, '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', Journal of Medicinal Chemistry, vol. 55, no. 20, pp. 8969-8973. https://doi.org/10.1021/jm3012189

Pokhrel, Laxman ; Maezawa, Izumi ; Nguyen, Thi D T ; Chang, Kyeong Ok ; Jin, Lee-Way ; Hua, Duy H. / 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. In: Journal of Medicinal Chemistry. 2012 ; Vol. 55, No. 20. pp. 8969-8973.

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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

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