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Open AccessArticle

Synthetic Chalcones with Potent Antioxidant Ability on H2O2-Induced Apoptosis in PC12 Cells

1
Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China
2
Institute of Sports Science, Wenzhou Medical University, Wenzhou 325035, China
3
College of Information Science and Computer Engineering, Wenzhou Medical University, Wenzhou 325035, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2014, 15(10), 18525-18539; https://doi.org/10.3390/ijms151018525
Received: 27 August 2014 / Revised: 24 September 2014 / Accepted: 28 September 2014 / Published: 14 October 2014
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells 2014)
Chalcone derivatives (E)-3-(4-hydroxy-3-methoxyphenyl)-1-(4-methoxyphenyl) prop-2-en-1-one and (E)-3-(4-hydroxyphenyl)-1-(4-methoxyphenyl) prop-2-en-1-one (Compounds 1 and 2) have been demonstrated to be potent anti-inflammatory agents in our previous study. In light of the relationship of intracellular mechanisms between anti-inflammatories and antioxidants, we further designed and synthesized a series of chalcone derivatives based on 1 and 2, to explore their antioxidant efficacy. The majority of the derivatives exhibited strong protective effects on PC12 (PC12 rat pheochromocytoma) cells exposed to H2O2, and all compounds were nontoxic. A preliminary structure-activity relationship was proposed. Compounds 1 and 1d ((E)-2-methoxy-4-(3-(4-methoxyphenyl)-3-oxoprop-1-en-1-yl) phenyl acrylate) exerted the action in a good dose-dependent manner. Quantitative RT-PCR (qRT-PCR) and western blot analysis showed that 1 and 1d significantly improve the expression of nuclear factor erythroid 2 p45-related factor 2 (Nrf2)-dependent antioxidant genes g-Glutamylcysteine Ligase Catalytic Subunit (GCLC) and heme oxygenase-1 (HO-1) and their corresponding proteins (γ-glutamyl cysteine synthase (γ-GCS) and HO-1) in PC12 cells. Inhibition of GCLC and HO-1 by specific inhibitors, l-buthionine-S-sulfoximine (BSO) and zinc protoporphyrin (ZnPP), respectively, partially reduce the protective effect of 1 and 1d. These data present a series of novel chalcone analogs, especially compounds 1 and 1d, as candidates for treating oxidative stress-related disease by activating the Nrf2-antioxidant responsive element (ARE) pathway. View Full-Text
Keywords: chalcone derivatives; antioxidant; PC12 cells; Nrf2-ARE pathway; GCLC; HO-1 chalcone derivatives; antioxidant; PC12 cells; Nrf2-ARE pathway; GCLC; HO-1
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Wu, J.-Z.; Cheng, C.-C.; Shen, L.-L.; Wang, Z.-K.; Wu, S.-B.; Li, W.-L.; Chen, S.-H.; Zhou, R.-P.; Qiu, P.-H. Synthetic Chalcones with Potent Antioxidant Ability on H2O2-Induced Apoptosis in PC12 Cells. Int. J. Mol. Sci. 2014, 15, 18525-18539.

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