基于萘普生-芳基金属配合物的抗癌及抗炎性能

doi:10.7503/cjcu20190534

高等学校化学学报 ›› 2020, Vol. 41 ›› Issue (2): 243.doi: 10.7503/cjcu20190534

基于萘普生-芳基金属配合物的抗癌及抗炎性能

薛旭玲,陈俊,张自由,王萌萌,吕梦迪,郝元元,胡炯圣,葛超,苏志(),钱勇,刘红科()

南京师范大学化学与材料科学学院, 南京 210023

收稿日期:2019-10-15 出版日期:2020-02-10 发布日期:2019-12-19
通讯作者: 苏志,刘红科 E-mail:zhisu@njnu.edu.cn;liuhongke@njnu.edu.cn
基金资助:
国家自然科学基金重点国际合作项目(21420102002);国家自然科学基金(21771109);国家自然科学基金(21778033);国家自然科学基金(21807060);江苏省333工程人才专项基金;江苏省六大人才高峰和江苏省自然科学基金(BE2013716);江苏省六大人才高峰和江苏省自然科学基金(BK20171472);中国博士后基金资助.(2019M651874)

Arene-metal Complexes Based on Naproxen for Antitumor and Anti-inflammatory Applications ^†

XUE Xuling,CHEN Jun,ZHANG Ziyou,WANG Mengmeng,Lü Mengdi,HAO Yuanyuan,HU Jiongsheng,GE Chao,SU Zhi(),QIAN Yong,LIU Hongke()

School of Chemistry and Materials Science, Nanjing Normal University, Nanjing 210023, China

Received:2019-10-15 Online:2020-02-10 Published:2019-12-19
Contact: Zhi SU,Hongke LIU E-mail:zhisu@njnu.edu.cn;liuhongke@njnu.edu.cn
Supported by:
? Supported by the Key International Joint Research Program of the National Natural Science Foundation of China(21420102002);the National Natural Science Foundation of China(21771109);the National Natural Science Foundation of China(21778033);the National Natural Science Foundation of China(21807060);the “333 Talent Project” of Jiangsu Province of China, the “Summit of the Six Top Talents” Program of Jiangsu Province of China;the “Summit of the Six Top Talents” Program of Jiangsu Province of China, the Natural Science Foundation of Jiangsu Province, China(BE2013716);the “Summit of the Six Top Talents” Program of Jiangsu Province of China, the Natural Science Foundation of Jiangsu Province, China(BK20171472);the China Postdoctoral Science Foundation(2019M651874)

1. ESM to 243-252.pdf.pdf(505KB)

摘要/Abstract

摘要：

以萘普生(NPX)为前体, 分别与芳基钌(Ru)、锇(Os)及铱(Ir)二聚体反应制备了3个单核配合物[Ru(η ⁶-p-cymene)(NPX-bpy)Cl]Cl(1), [Os(η ⁶-p-cymene)(NPX-bpy)Cl]Cl(2)和[Ir(η ⁵-Cp ^*)·(NPX-bpy)Cl]Cl(3). 利用元素分析、电喷雾质谱和核磁共振波谱对3个配合物的组成和结构进行了表征, 并研究了其细胞毒性. 结果表明, 3个配合物对几种肿瘤细胞株均无毒性(IC₅₀>100 μmol/L), 仅配合物1对NB-4细胞有中等程度的毒性(IC₅₀=45.2 μmol/L), 且毒性大于配合物2和3, 这可能与配合物1在细胞核内具有更高的富集量有关. 此外, 3个配合物均可有效抑制COX-2的表达, 保留了萘普生的抗炎性质, 实现了金属配合物抗癌及抗炎的多功能化应用.

关键词: 芳基金属, 抗癌药物, 抗炎, 环氧合酶

Abstract:

Naproxen(NPX) was used as precursors to prepare three arene complexes[Ru(η ⁶-p-cymene)·(NPX-bpy)Cl]Cl(1), [Os(η ⁶-p-cymene)(NPX-bpy)Cl]Cl(2) and [Ir(η ⁵-Cp ^*)(NPX-bpy)Cl]Cl(3) with arene ruthenium(Ru), osmium(Os) and iridium(Ir) dimers. The complexes were characterized by elemental analysis, electrospray ionization mass spectrometry and nuclear magnetic resonance spectroscopy. The cytotoxicity results showed that the three complexes exhibited little cytotoxic activity against the tumor cell lines(IC₅₀>100 μmol/L), except that complex 1 has moderate activity on NB-4 cells(IC₅₀=45.2 μmol/L), which may be attributed to the higher enrichment of complex 1 in the nucleus than complex 2 and 3. In addition, the three complexes could effectively inhibit the expression of COX-2, equivalent to the anti-inflammatory properties of naproxen, and achieved the multi-functional application of anticancer and anti-inflammatory threapy of arene-metal complexes.

Key words: Arene-metal complex, Anticancer drug, Anti-inflammation, Cyclooxygenase-2

中图分类号:

O614

TrendMD:

薛旭玲,陈俊,张自由,王萌萌,吕梦迪,郝元元,胡炯圣,葛超,苏志,钱勇,刘红科. 基于萘普生-芳基金属配合物的抗癌及抗炎性能. 高等学校化学学报, 2020, 41(2): 243.

XUE Xuling,CHEN Jun,ZHANG Ziyou,WANG Mengmeng,Lü Mengdi,HAO Yuanyuan,HU Jiongsheng,GE Chao,SU Zhi,QIAN Yong,LIU Hongke. Arene-metal Complexes Based on Naproxen for Antitumor and Anti-inflammatory Applications ^†. Chem. J. Chinese Universities, 2020, 41(2): 243.

图/表 8

Scheme 1 Synthetic routes of target complexes 1—3

Table 1 IC50(μmol/L) data of compounds against several cell lines in vitro

Complex	IC₅₀/(μmol·L^-1)
Complex	HeLa	A549	A2780	NB-4
NPX-bpy	>200	>200	>200	>200
1	>200	>200	120.3±1.9	45.2±2.0
2	>200	>200	108.4±4.2	78.6±2.3
3	167.8±2.4	118.3±4.7	109.8±3.3	101.4±1.9
CDDP	1.6±1.2	17.9±0.9	10.0±1.7	4.2±1.1

Fig.2 Inhibition of COX-2 activity after treated with different concentrations of complexes 1—3

Fig.3 Fluorescent spectra of complex 1—3 in aqueous solution(containing 5% DMSO) λex=270 nm.

Fig.4 UV-Vis spectra of complexes 1(A), 2(B) and 3(C) in H2O solution(containing 5% DMSO) incubation for 24 h at 298 K to detect the hydrolysis of the complexes and the absorbance intensity statistics of the complexes 1—3 for different incubation time(D)

Fig.5 CD spectra of CT-DNA bound by complexes 1—3(A—C) with different [complex]/[DNA] values

Fig.6 Gel electrophoresis assay of pBR322 DNA treated with different concentrations of complexes 1—3(A—C)

Fig.7 Intracellular concentrations of metal ions(Ru, Os and Ir) in different organelles after treated with complexes 1—3 using ICP-MS detection

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基于萘普生-芳基金属配合物的抗癌及抗炎性能

Arene-metal Complexes Based on Naproxen for Antitumor and Anti-inflammatory Applications ^†

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基于萘普生-芳基金属配合物的抗癌及抗炎性能

Arene-metal Complexes Based on Naproxen for Antitumor and Anti-inflammatory Applications †

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Arene-metal Complexes Based on Naproxen for Antitumor and Anti-inflammatory Applications ^†