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

International Journal of Molecular Sciences

Jian-Zhang Wu¹  Chan-Chan Cheng¹  Lai-Lai Shen¹  Zhan-Kun Wang³  Shou-Biao Wu¹  Wu-Lan Li²  Su-Hua Chen¹  Rong-Ping Zhou¹  Pei-Hong Qiu¹ 

[1] Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China; E-Mails:;College of Information Science and Computer Engineering, Wenzhou Medical University, Wenzhou 325035, China; E-Mail:;Institute of Sports Science, Wenzhou Medical University, Wenzhou 325035, China; E-Mail:

关键词: chalcone derivatives;    antioxidant;    PC12 cells;    Nrf2-ARE pathway;    GCLC;    HO-1;   

DOI  :  10.3390/ijms151018525

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.