新合成的柠檬醛衍生物是 HepG2 细胞的新型抑制剂

IF 2.5 4区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY
Wei Gao, Xiaoju Hua, Shengliang Liao, Zhikai Xiahou, Haikuan Yang, Lifang Hu, Yunyang Chi
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引用次数: 0

摘要

由 6-甲基吡啶-2,4-二醇和柠檬醛合成的 2H 吡喃化合物 1 在铜催化下与一系列芳基硼酸发生 N-芳基化反应,得到芳基化的吡喃吡啶核心结构衍生物(收率高达 77%)。其中,化合物 3 h 对 HepG2 肝癌细胞的抑制效果比柠檬醛好得多,与新合成的衍生物(本文简称 3 h)接触后的 IC50 值为 5.3 μM,低于顺铂的 IC50 值(6.5 μM)。同时,随着药物浓度的增加,HepG2细胞的细胞周期停滞在S期,细胞凋亡率显著增加。此外,实时荧光定量 PCR 和 Western 印迹实验表明,凋亡蛋白 BAX 的表达增加,而抗凋亡蛋白 BCL2 的表达受到抑制,且呈剂量依赖性。此外,3 h 还能有效降低 PI3 K、ATK 和 ERK 的磷酸化水平,从而抑制 MAPK/ERK 和 PI3 K/ATK 信号通路。简而言之,3 h 对 HepG2 肝癌细胞的存活有抑制作用,未来可用作抗癌药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Newly Synthesized Citral Derivatives Serve as Novel Inhibitor in HepG2 Cells

Newly Synthesized Citral Derivatives Serve as Novel Inhibitor in HepG2 Cells

2H-pyran compound 1 synthesized from 6-methylpyridine-2,4-diol and citral, has been used for Cu-catalyzed N-arylation with a range of arylboric acids to obtain arylated pyranopyridine core structure derivatives (yield up to 77 %). Among them, compound 3 h exhibited a much better inhibitory effect on HepG2 liver cancer cells compared to citral, and the IC50 value was 5.3 μM following exposure with the newly synthesized derivatives (herein named 3 h for short in this paper), which was lower than that of the cisplatin (6.5 μM). Meanwhile, the cell-cycle arrest of HepG2 cells occurred in the S phase, and the apoptosis of HepG2 cells was significantly increased with increasing drug concentration. In addition, real-time fluorescence quantification PCR and Western blotting experiments showed that the expression of apoptotic protein BAX was increased, while the expression of anti-apoptotic protein BCL2 was inhibited in a dose-dependent fashion. The results of these experiments indicated that apoptosis was promoted in HepG2 cells via apoptotic signaling pathway activated by 3 h. Furthermore, 3 h effectively decreased the phosphorylation levels of PI3 K, ATK and ERK, resulting in the inhibitions of MAPK/ERK and PI3 K/ATK signaling pathways. Briefly, 3 h has been found to show inhibitory effects on the survival of HepG2 liver cancer cells and may be used as anti-cancer drug in the future.

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来源期刊
ChemistryOpen
ChemistryOpen CHEMISTRY, MULTIDISCIPLINARY-
CiteScore
4.80
自引率
4.30%
发文量
143
审稿时长
1 months
期刊介绍: ChemistryOpen is a multidisciplinary, gold-road open-access, international forum for the publication of outstanding Reviews, Full Papers, and Communications from all areas of chemistry and related fields. It is co-owned by 16 continental European Chemical Societies, who have banded together in the alliance called ChemPubSoc Europe for the purpose of publishing high-quality journals in the field of chemistry and its border disciplines. As some of the governments of the countries represented in ChemPubSoc Europe have strongly recommended that the research conducted with their funding is freely accessible for all readers (Open Access), ChemPubSoc Europe was concerned that no journal for which the ethical standards were monitored by a chemical society was available for such papers. ChemistryOpen fills this gap.
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