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JOURNAL OF MOLECULAR STRUCTURE · 2024 · IF 4

Synthesis and anti-cancer investigations of copper(II) complexes based on adenine

Xiaoyan Zhai,Hussein Hanibah,Nor Zakiah Nor Hashim,Juzheng Zhang,Xianli Ma,Lilan Wei,Xiaoqun Zhou

Platinum-based chemotherapeutics have played a critical role in oncology for decades. However, their broader utility is hindered by the advent of severe side effects and the emergence of drug resistance. The pursuit of alternative agents, particularly non-platinum (non-Pt) metal complexes, has gained momentum in current research. Designing efficacious non-Pt metal agents that target DNA poses a complex challenge. In this study, we present the strategic design, synthesis, and thorough characterization of two innovative copper(II) complexes leveraging adenine as a ligand, a potential avenue to overcome these challenges. Our investigation demonstrates the superior cytotoxicity of these copper(II) complexes compared to the benchmark cisplatin, with complex C2 exhibiting the most promising anticancer activity, showcasing an impressive IC 50 value of 4.51 μM in MGC-803 cells. Mechanistic insights underscore that complex C2 executes its cytotoxic effects by instigating DNA damage, orchestrating cell cycle arrest at the G2 phase, perturbing mitochondrial membrane potential, inducing ROS production, and ultimately triggering apoptotic pathways. These findings significantly emphasize the potential of designing novel adenine-based anticancer metal complexes targeting DNA, portraying a compelling trajectory for advancing anticancer drug development.

CAS / MDL: 7447-39-4 5404-86-4
研究领域: 药理学 · 肿瘤学 · 生物化学
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APPLIED ORGANOMETALLIC CHEMISTRY · 2019 ·Vol. 34 ·期 1 ·e5264 · IF 3.259

Syntheses, crystal structure and biological evaluation of three novel Cu (II) complexes with Schiff base derived from fluorinated amino acid and Salicylaldehyde

Ruixue Wu,Caifeng Bi,Xia Zhang,Ziao Zong,Chuanbin Fan,Xiaoyin Zhang,Nana Li,Yuhua Fan

Three novel Cu (II) coordination complexes, formulated as [Cu 3 (C 14 H 8 NO 3 F) 2 (CH 3 COO) 2 ] n ( 1 ), [Cu 2 (C 14 H 9 NO 3 F) 2 (CH 3 COO)Cl] ( 2 ) and [Cu(C 14 H 8 NO 3 F)(CH 3 OH) 2 ] ( 3 ), have been synthesized by 3-Fluoroanthranilic acid, Salicylaldehyde and Cu (II) salt as sources in different reaction conditions and characterized by single crystal X-ray diffraction, X-ray powder diffraction, IR spectroscopy and elemental analysis. Single-crystal diffraction analysis revealed that the complexes exhibited different coordination modes and conformations which were linked into multidimensional networks through some weak interactions. The biological activities vary greatly on account of the different Cu (II) numbers among the three complexes. In order to discuss the bioactivities, the complexes have been screened for antimicrobial activities against E. coli and S. aureus , antitumor activities against A549 (human lung cancer cells), Hela (human cervical cancer cells) and HepG-2(human liver hepatocellular carcinoma cells). Their interactions with calf thymus DNA were investigated by UV–visible and fluorescence spectrometry, as well as viscosity measurements. Interestingly, 1 (the rare 3-core Cu (II) coordination polymer) shows great antibacterial activities and highest DNA binding affinities. Antitumor studies revealed that complex 1 also exhibited highest activity.

CAS / MDL: 95-01-2 825-22-9 90-02-8
研究领域: 配位化学 · 生物无机化学 · 药物化学
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INORGANICA CHIMICA ACTA · 2015 · IF 2.046

Synthesis, characterization and anticancer activity of two ternary copper(ІІ) Schiff base complexes

Xin Li,Cheng Fang,Ziao Zong,Liansheng Cui,Caifeng Bi,Yuhua Fan

Two ternary copper(II) Schiff base complexes 2Cu(C 14 H 8 NO 3 F)(C 12 H 8 N 2 )·3CH 3 OH ( 1 ) and 2Cu(C 14 H 8 NO 3 Cl)(C 12 H 8 N 2 )·3CH 3 OH ( 2 ) were synthesized and characterized by IR spectroscopy, elemental analysis, and single crystal X-ray diffraction. X-ray crystallography shows that both of the copper atoms adopt square pyramidal geometry. Each copper atom is five coordinated by one nitrogen atom from –C N–, two nitrogen atoms from 1,10-phenanthroline, one hydroxyl oxygen atom and one carboxylate oxygen atom. The proteasome is often found to be overactive in cancer cells. It has also been found that cancer cells are more sensitive to proteasome inhibition than normal cells. Therefore proteasome inhibitors are pursued as antitumor drugs. The anticancer activity of the two complexes was studied. The results showed that complex ( 1 ) can significantly inhibit the cellular proliferation of human breast cancer MDA-MB-231 cells. In addition, it has proteasome-inhibitory activity in human breast cancer MDA-MB-231 cells. The inhibition of the tumor proteasomal activity resulted in the accumulation of ubiquitinated proteins and ubiquitinated form of IκB-α, (a natural proteasome substrate) followed by induction of apoptosis. The results suggest that the fluorine-containing copper complex, as a potent proteasome inhibitor, has potential to be developed into a novel anticancer drug.

研究领域: 无机化学 · 药理学 · 肿瘤学
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TRANSITION METAL CHEMISTRY · 2018 ·Vol. 43 ·期 3 ·259-271 · IF 1.261

DNA binding, crystal structure, molecular docking studies and anticancer activity evaluation of a copper(II) complex

Liu Ya-Xian,Mo Hui-Wen,Lv Zhen-Yu,Shen Fang,Zhang Chun-Lian,Qi Yong-Yu,Mao Zong-Wan,Le Xue-Yi

A copper complex [Cu(HPBM)( l -Phe)(H 2 O)]·ClO 4 (1) (HPBM = 5-methyl-2-(2′-pyridyl)benzimidazole, l -Phe =  l -phenylalanine anion) was synthesized and characterized by elemental analysis, IR, ESI–MS, HR–ESI–MS, ESR spectroscopy, and by X-ray single-crystal analysis. The binding constant of the complex with calf thymus DNA (CT-DNA) was determined as 7.38 (± 0.57) × 10 4  M −1 . Further studies indicated that the complex interacts with CT-DNA through minor groove binding. The in vitro cytotoxic activities of both the free proligand and the complex against Eca-109, HeLa and A549 cancer cells and normal LO2 cells were evaluated by the MTT method. The IC 50 values range from 5.7 ± 0.1 to 8.3 ± 0.6 µM. Free HPBM displays no cytotoxic activity against the selected cancer cells, with IC 50 values more than 100 µM. Double staining analysis showed that the complex can induce apoptosis in Eca-109 cells. Comet assays demonstrated that the complex can damage DNA and cause apoptosis. The complex also induces an increase in intracellular reactive oxygen species and a reduction in mitochondrial membrane potential. The complex can also increase the intracellular Ca 2+ level and induce release of cytochrome c . The cell cycle arrest was investigated by flow cytometry. The results demonstrate that the complex induces apoptosis in Eca-109 cells through DNA-binding and ROS-mediated mitochondrial dysfunctional pathways.

CAS / MDL: 63-91-2
研究领域: 生物化学 · 药理学 · 肿瘤学
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INORGANICA CHIMICA ACTA · 2016 · IF 1.918

Multi-properties of a Cu(II) complex: Crystal structure, anion binding ability, bioactivity and cell cytotoxicity

Xuefang Shang,Kui Ren,Jie Li,Wanli Li,Jiajia Fu,Xueli Zhang,Jinlian Zhang

A new copper(II) complex based on Schiff bases of 3-nitrosalicylaldehyde was synthesized and the crystal was also obtained fortunately. Its structure was well characterized by single-crystal X-ray diffraction and HRMS. The complex showed the strongest binding ability and high selectivity for hydrogen sulfide among other anions (AcO − , H 2 PO 4 − , F − , Cl − , Br − and I − ) at neutral pH in organic-aqueous solutions. The possible mechanism was the copper ion was released and combined with hydrogen sulfide after the anion was added. In addition, the further application of the sensor was applied to hela cells cytotoxicity. The above results indicated the copper(II) complex could be used as a sensor for the detection of HS − in the sample of environment, pharmacy, and etc. More importantly, the copper(II) complex also exhibited effective and wide antibacterial activity.

研究领域: 化学 · 生物学 · 医学
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Journal of Sulfur Chemistry · 2018 · IF 1.32

Highly selective probes of copper(II) complexes for sulfide detection and cytotoxicity assay

Yanmei Chen,Xuefang Shang,Xing Zhao,Jie Li,Jianmei Yuan,Hongli Chen,Jinlian Zhang,Tianyun Wang

Two probes based on novel Copper(II) complexes were developed in order to obtain H2S molecular probes with higher selectivity. The molecular structures of the complexes were characterized by 1H NMR, HRMS, IR and elemental analysis. The interaction of the compounds with biologically important anions and amino acids was determined by UV-vis and Fluorescence titration experiments. Results indicated that the compounds showed the highest binding ability for HS− among studied anions (AcO−, H2PO4−, F−, Cl−, Br− and I−) and amino acids (GSH, HCys and Cys) accompanied by blue shift phenomenon in pure DMSO and aqueous solution. The possible mechanism of host–guest interaction may be that the Copper(II) ion of complex was captured by HS− and free ligand released which showed a remarkable changes in UV-vis absorption. In addition, cytotoxicity of the synthesized compounds was studied on MCF-7 cells. Results indicated that the synthesized compounds had low cytotoxicity over a concentration range of 0–150 µg⋅mL−1, which exhibited that the synthesized probes could be used to detect H2S in vivo.The probes based on novel copper(II) complexes were synthesized and obtained by the reaction of substituent salicylaldehyde with amine derivatives, and then reacted with Cu(CH3COO)2·H2O, respectively. Investigation on the interference from other species suggested that copper(II) complexes have high selectivity for HS− over other anions (AcO−, , F−, Cl−, Br− and I−), followed by the release of the copper ion to give a remarkable increase in UV–VIS absorption in pure DMSO solution and aqueous solution.

研究领域: 分析化学 · 生物化学 · 医学
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TALANTA · 2012 · IF 3.794

Ionic liquids with amino acids as cations: Novel chiral ligands in chiral ligand-exchange capillary electrophoresis

Xiaoyu Mu,Li Qi,Haizhi Zhang,Ying Shen,Juan Qiao,Huimin Ma

Ionic liquids (ILs) with l -proline ( l -Pro) as cations have been developed for the novel chiral ligands coordinated with Cu(II) in chiral ligand exchange capillary electrophoresis (CLE-CE). Four kinds of amino acid ionic liquids (AAILs), including [ l -Pro][CF 3 COO], [ l -Pro][NO 3 ], [ l -Pro][BF 4 ] and [ l -Pro 2 ][SO 4 ], were successfully synthesized. Among them, [ l -Pro][CF 3 COO] was selected as the model ligand to optimize the separation conditions. The influences of AAIL concentration, pH, and methanol concentration on efficiency of chiral separation were investigated. Then it has been testified that the optimal buffer solution consisted of 25.0   mM Cu(Ac) 2 , 50.0   mM AAIL and 20% (v/v) methanol at pH 4.0. The interesting thing is well enantioresolution could be observed with [ l -Pro][CF 3 COO] as the new chiral ligand and nine pairs of labeled d , l -AAs were successfully separated with the resolution ranging from 0.93 to 6.72. Meanwhile, the baseline separation of labeled d , l -AAs could be achieved with the other three kinds of AAILs as ligands. The results have demonstrated the good applicability of AAILs with AAs as cations for chiral separation in CLE-CE system. In addition, comparative study was also conducted for exploring the mechanism of the AAILs as new ligands in CLE-CE.

研究领域: 分析化学 · 手性化学
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INORGANIC CHEMISTRY COMMUNICATIONS · 2018 · IF 1.81

Design, synthesis, crystal structure and cytotoxicity studies of colorimetric fluorescent “OFF-ON” probes for rapid detection of hydrogen sulfide based on Cu(II) complex

Xuefang Shang,Xuejing Yue,Yanmei Chen,Congshu Li,Hongli Chen,Tianyun Wang

Four colorimetric fluorescent probes based on copper(II) complexes were synthesized and the molecular structures were characterized by X-ray diffraction, ESI-HRMS and elemental analysis . When exposed to HS − , the synthesized probes showed significant color changes from yellow to red and remarkable increase of fluorescence intensity (over 80-fold). What's more, the interaction of host-guest could be completed in 2 min. However, no clear color and fluorescence intensity changes were observed in the presence of other anions (AcO − , H 2 PO 4 − , F − , Cl − , Br − , I − , SO 4 2− , SO 3 2− , CO 3 2− , Cys and GSH). The synthesized colorimetric fluorescent probes could detect HS − rapidly and conveniently. Cytotoxicity studies indicated that the synthesized fluorescent probes were low cytotoxicity in Hela cells and may be used to detect H 2 S level in vivo.

研究领域: 化学 · 生物学 · 医学
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Materials · 2022 ·Vol. 15 ·期 5 ·1719 · IF 3.748

An Efficient Cyan Emission from Copper (II) Complexes with Mixed Organic Conjugate Ligands

Jingjing Wang,Junjie Ren,Qinglin Tang,Xinzhi Wang,Yao Wang,Yanxin Wang,Zhonglin Du,Wei Wang,Linjun Huang,Laurence A. Belfiore,Jianguo Tang

Copper (II) complexes containing mixed ligands were synthesized in dimethyl formamide (DMF). The intense cyan emission at an ambient temperature is observed for solid copper (II) complexes with salicylic acid and a 12% quantum yield with a fluorescent lifetime of approximately 10 ms. Hence, copper (II) complexes with salicylic acid are excellent candidates for photoactive materials. Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) reveal that the divalent copper metal centers coordinate with the nitrogen and oxygen lone pairs of conjugate ligands. XPS binding energy trends for core electrons in lower-lying orbitals are similar for all three copper (II) complexes: nitrogen 1s and oxygen 1s binding energies increase relative to those for undiluted ligands, and copper 2p3/2binding energies decrease relative to that for CuCl2. The thermal behavior of these copper complexes reveals that the thermal stability is characterized by the following pattern: Cu(1,10-phenanthroline)(salicylic acid) > Cu(1,10-phenanthroline)(2,2’-bipyridine) > Cu(1,10-phenanthroline)(1-benzylimidazole)2.Keywords:copper (II) complex;luminescent materials;benzylimidazole;bipyridine;salicylic acid;spectroscopy

研究领域: 无机化学 · 材料科学
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Foods · 2024 ·Vol. 13 ·期 4 ·591 · IF 4.7

Hesperitin-Copper(II) Complex Regulates the NLRP3 Pathway and Attenuates Hyperuricemia and Renal Inflammation

Xi Peng,Kai Liu,Xing Hu,Deming Gong,Guowen Zhang

Background: Hyperuricaemia (HUA) is a disorder of purine metabolism in the body. We previously synthesized a hesperitin (Hsp)-Cu(II) complex and found that the complex possessed strong uric acid (UA)-reducing activity in vitro. In this study we further explored the complex’s UA-lowering and nephroprotective effects in vivo. Methods: A mouse with HUA was used to investigate the complex’s hypouricemic and nephroprotective effects via biochemical analysis, RT-PCR, and Western blot. Results: Hsp-Cu(II) complex markedly decreased the serum UA level and restored kidney tissue damage to normal in HUA mice. Meanwhile, the complex inhibited liver adenosine deaminase (ADA) and xanthine oxidase (XO) activities to reduce UA synthesis and modulated the protein expression of urate transporters to promote UA excretion. Hsp-Cu(II) treatment significantly suppressed oxidative stress and inflammatory in the kidney, reduced the contents of cytokines and inhibited the activation of the nucleotide-binding oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) inflammatory pathway. Conclusions: Hsp-Cu(II) complex reduced serum UA and protected kidneys from renal inflammatory damage and oxidative stress by modulating the NLRP3 pathway. Hsp-Cu(II) complex may be a promising dietary supplement or nutraceutical for the therapy of hyperuricemia.

研究领域: 药理学 · 生物化学 · 分子生物学 · 炎症研究
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RSC Advances · 2023 ·Vol. 13 ·期 38 ·26324-26329 · IF 3.9

A novel tetranuclear Cu(II) complex for DNA-binding and in vitro anticancer activity

Shuhua Cao,Anlin Wang,Kaoxue Li,Zhiteng Lin,Hongwei Yang,Xiaolei Zhang,Jianmei Qiu,Xishi Tai

A novel tetranuclear Cu(II) complex (TNC) was successfully synthesized and characterized by X-ray single crystal diffraction. The interaction of the complex with calf thymus DNA (CT-DNA) has been studied by UV-vis absorption titration, fluorescence technology and molecular docking. The results indicated that TNC could bind to the DNA through an intercalative mode. The agarose gel electrophoresis experiment showed that TNC could cleave supercoiled plasmid DNA into linear DNA. The anticancer activity of TNC was tested on four cancer cell lines: MCF7, A549, 4T1 and HepG2. The results indicated that TNC shown significant activity against all of above cell lines.

CAS / MDL: 109-55-7 4755-77-5
研究领域: 生物化学 · 分子生物学 · 药理学
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INORGANICA CHIMICA ACTA · 2020 · IF 2.304

Synthesis, crystal structures and photo-thermal properties of five naphthyl-functionalized Copper(II) coordination compounds

Hao-Hai Wang,Jing-Zhe Li,Jing Nie,Zi-Xuan Yao,Hong-Jing Li,Kuan-Guan Liu,Xiao-Wei Yan

For achieving solar absorber and conversion molecular materials with excellent photothermal conversion ability, five mononuclear Copper(II) coordination compounds have been designed and isolated. They are fully characterized by IR, Powder XRD, Solid-state UV, and TGA. Single-crystal X-ray structural analysis reveals that they are typical photothermal conversion molecules with double chromophores: one antenna chromophore (NT group here) and the second chromophores (Cu(dmap) 4 2+ , Cu(dmap) 2 2+ , Cu(bpy) 2 2+ and Cu(phen) 2 2+ ). Both chromophores have great influence on their solid-state optical absorption. Their photothermal conversion experiments show that compounds 3 , 4 and 5 have the better results (the highest temperature increment 21.7 ℃ and equilibrium temperature ~ 60.7 ℃) than compounds 1 and 2 . Those results give some clues for illustrating the molecular mechanisms of solar absorber and photothermal conversion molecular materials.

研究领域: 无机化学 · 材料科学
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