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Mol Pharm. 2014 Feb 3;11(2):428-35. doi: 10.1021/mp400395g. Epub 2013 Dec 26.

Antioxidant and antiapoptotic effects of 1,1'-(biphenyl-4,4'-diyl)-bis(3-(dimethylamino)-propan-1-one) on protecting PC12 cells from Aβ-induced injury.

Author information

1
Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University , Southern Renmin Road, No. 17, Section 3, Chengdu 610041, P. R. China.

Abstract

Abnormal extracellular deposition of β-amyloid (Aβ) is thought to play a key role in the pathogenesis of Alzheimer's disease (AD). Preventing Aβ-induced neurotoxicity has become a potential therapeutic approach to improve the onset and progression of AD. Here we report the synthesis of 1,1'-(biphenyl-4,4'-diyl)-bis(3-(dimethylamino)-propan-1-one) (BDBDP) and evaluate whether it protects PC12 cells from Aβ1-42-induced cytotoxicity in PC12 cells. Treating cells with Aβ1-42 significantly reduced cell viability and mitochondrial membrane potential while also significantly increasing apoptosis and production of reactive oxygen species (ROS). Pretreating the cells with BDBDP significantly ameloriated these Aβ1-42-induced effects. Futhermore, BDBDP strongly reduced pro-apoptotic signaling in response to ROS by reducing levels of activated caspase-3 and increasing the ratio of Bcl-2 to Bax. These findings provide evidence that BDBDP protects against Aβ1-42-induced neurotoxicity in PC12 cells by inhibiting oxidative stress and cell apoptosis.

PMID:
24350730
DOI:
10.1021/mp400395g
[Indexed for MEDLINE]

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