Proteasome inhibition and cytostatic effects on human cancer cells by pyrazolone-enamines: a combined crystallographic, structural and computational study

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	Proteasome inhibition and cytostatic effects on human cancer cells by pyrazolone-enamines: a combined crystallographic, structural and computational study
	Yan, Xingchen 1,2; Xu, Jiakun 1,3; Wu, Xiaojing 1; Zhang, Zhongyu 1; Zhang, Xia 1; Fan, Yuhua 1; Bi, Caifeng 1
刊名	NEW JOURNAL OF CHEMISTRY
	2015
卷号	39 期号:3 页码:2168-2180
英文摘要	Nine compounds were designed and synthesized by the condensation reaction of the carbonyl in 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one (HPMBP) with the amino groups in 5-aminoisophthalic acid, 4,40-diaminodiphenylmethane, 4-aminophenylacetic acid, 4-aminobenzamide, 2-amino-4-methylphenol, 5-amino-2-methylphenol, 2-aminophenol, 3-aminophenol and 4-aminophenol. They were then characterized by IR, H-1 NMR, elemental analysis, and X-ray crystallography, which suggested that all of them exist as the pyrazolone-enamine forms in the solid state and in a DMSO solution through tautomeric reactions. The nine compounds (compounds 1-9) were evaluated for their ability to inhibit the proliferation of human liver cancer HepG2 cells. Compounds 5, 6, 7 and 8 demonstrated a strong inhibitory effect on the proliferation of HepG2 cells. The nine compounds can also inhibit the activity of the human cancer cellular 20S proteasome. Further studies on compound 6 as the representative indicate that it can cause the accumulation of ubiquitinated proteins and the proteasome target proteins Bax and p27, and exhibit a cytostatic effect in HepG2 cells in a concentration-dependent and time-dependent manner. The four potential tautomers of compound 6 were optimized and their single point energies were calculated by the density functional theory (DFT) B3LYP method based on the polarized continuum model (PCM) in water to identify the most likely tautomer existing in cancer cells. Based on the optimized structure of the most stable tautomer in water, the Wiberg bond orders, molecular electrostatic potential (MEP) maps and frontier molecular orbital were calculated. As compounds 5, 6, 7 and 8 have hydroxyl in the ortho-position or meta-position, our study can provide some information to study their anticancer mechanism and the substitution effect of different functional groups.
WOS标题词	Science & Technology ; Physical Sciences
类目[WOS]	Chemistry, Multidisciplinary
研究领域[WOS]	Chemistry
关键词[WOS]	TETRADENTATE SCHIFF-BASES ; SPECTROPHOTOMETRIC DETERMINATION ; CRYSTAL-STRUCTURE ; COPPER-COMPLEXES ; METAL-COMPLEXES ; DERIVATIVES ; APOPTOSIS ; ANTICANCER ; INDUCTION ; TARGET
收录类别	SCI
语种	英语
WOS记录号	WOS:000350896000064
公开日期	2015-12-24
内容类型	期刊论文
源URL	[http://ir.qibebt.ac.cn/handle/337004/6405]
专题	青岛生物能源与过程研究所_单细胞中心
作者单位	1.Ocean Univ China, Coll Chem & Chem Engn, Key Lab Marine Chem Theory & Technol, Minist Educ, Qingdao 266100, Shandong, Peoples R China 2.Chinese Acad Sci, Qingdao Inst Bioenergy & Bioproc Technol, Qingdao 266101, Peoples R China 3.Chinese Acad Fishery Sci, Yellow Sea Fisheries Res Inst, Key Lab Sustainable Dev Marine Fisheries, Minist Agr, Qingdao 266071, Peoples R China
推荐引用方式 GB/T 7714	Yan, Xingchen,Xu, Jiakun,Wu, Xiaojing,et al. Proteasome inhibition and cytostatic effects on human cancer cells by pyrazolone-enamines: a combined crystallographic, structural and computational study[J]. NEW JOURNAL OF CHEMISTRY,2015,39(3):2168-2180.
APA	Yan, Xingchen.,Xu, Jiakun.,Wu, Xiaojing.,Zhang, Zhongyu.,Zhang, Xia.,...&Bi, Caifeng.(2015).Proteasome inhibition and cytostatic effects on human cancer cells by pyrazolone-enamines: a combined crystallographic, structural and computational study.NEW JOURNAL OF CHEMISTRY,39(3),2168-2180.
MLA	Yan, Xingchen,et al."Proteasome inhibition and cytostatic effects on human cancer cells by pyrazolone-enamines: a combined crystallographic, structural and computational study".NEW JOURNAL OF CHEMISTRY 39.3(2015):2168-2180.