l-Ornithine Schiff base–copper and –cadmium complexes as new proteasome inhibitors and apoptosis inducers in human cancer cells

Zhang, Zhongyu; Bi, Caifeng; Yu, Fan; Zhang, Nan; Deshmukh, Rahul; Yan, Xingchen; Lv, Xiuwen; Zhang, Pengfei; Zhang, Xia; Dou, Q. Ping

doi:10.1007/s00775-014-1219-1

Cited by 23 publications

(10 citation statements)

References 36 publications

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“…3) are novel Cu-containing complexes that have been synthesized and compared for their abilities to inhibit the proliferation and induce apoptosis of MDA-MB-231 breast cancer and LNCaP human prostate cancer cells. HNO-Cu suppressed the proliferation in a dose-dependent manner, resulting in 95% inhibition of cell proliferation at 60 µM; however, DBO-Cu did not induce significant inhibition of cell proliferation in the cell lines (69). The anticancer activity is therefore dependent on the specific structure of the complex.…”

Section: Schiff Base Cu Complexesmentioning

confidence: 94%

Novel copper complexes as potential proteasome inhibitors for cancer treatment

Zhang

Wang

Yan

et al. 2016

Molecular Medicine Reports

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The use of metal complexes in the pharmaceutical industry has recently increased and as a result, novel metal‑based complexes have initiated an interest as potential anticancer agents. Copper (Cu), which is an essential trace element in all living organisms, is important in maintaining the function of numerous proteins and enzymes. It has recently been demonstrated that Cu complexes may be used as tumor‑specific proteasome inhibitors and apoptosis inducers, by targeting the ubiquitin‑proteasome pathway (UPP). Cu complexes have demonstrated promising results in preclinical studies. The UPP is important in controlling the expression, activity and location of various proteins. Therefore, selective proteasome inhibition and apoptotic induction in cancer cells have been regarded as potential anticancer strategies. The present short review discusses recent progress in the development of Cu complexes, including clioquinol, dithiocarbamates and Schiff bases, as proteasome inhibitors for cancer treatment. A discussion of recent research regarding the understanding of metal inhibitors based on Cu and ligand platforms is presented.

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Section: Schiff Base Cu Complexesmentioning

confidence: 94%

Novel copper complexes as potential proteasome inhibitors for cancer treatment

Zhang

Wang

Yan

et al. 2016

Molecular Medicine Reports

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“…[23] This indicated that the ligand preparation was done in good form. 1 H-NMR spectrum represented multiplet signals in the range 6.78-8.06 ppm which corresponded to the aromatic ring protons related to 14 H. [24,25] The spectrum also showed a single signal correlated to the phenolic protons (2H) that was appeared at 4.8 ppm. [26] The mass spectrum of the azo-dye ligand showed that the molecular ion peak is in good agreement with its suggested empirical formula.…”

Section: Characterization Of Azo-dye Ligand (H 2 L)mentioning

confidence: 97%

Metal complexes of tetradentate azo‐dye ligand derived from 4,4′‐oxydianiline: Preparation, structural investigation, biological evaluation and MOE studies

Deghadi

Mahmoud

Mohamed

2020

Applied Organom Chemis

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The Cr (III), Mn (II), Fe (III), Co (II), Ni (II), Cu (II) and Cd (II) complexes were prepared by reaction of its metal chlorides with new azo‐dye ligand (H2L). The ligand derived from 4,4′‐oxydianiline and 2‐amino‐4‐chlorophenol was synthesized in a 1:2 molar ratio. The structure of the ligand and its metal complexes was investigated using different tools such as elemental analysis (C, H, N and M), molar conductivity, IR, UV–vis, 1H‐NMR, mass spectrometry and thermogravimetric and differential thermogravimetric studies. The data showed that the ligand acted as a N,N,O,O‐binegative tetradentate ligand. All metal complexes had a octahedral structure as depicted by spectral and elemental analyses. The conductivity data showed the electrolytic nature of the Cr (III) and Fe (III) complexes while the other complexes were nonelectrolytes. Thermal analysis studies showed the decomposition of the complexes in four to five steps with the weight loss of hydrated water in the first decomposition step followed by the coordinated water and ligand molecules. Biological activity was tested for the prepared compounds against four bacterial species (Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa) and against two fungal species (Aspergillus fumigatus and Candida albicans). Also, all complexes were screened for anticancer activities against a breast cancer (MCF‐7) cell line. The [Co(L)(H2O)2] complex showed the lowest IC50 value. Molecular docking is a key tool in computer drug design. Therefore, investigation of protein receptors and ligand interaction plays a vital role in the design of structurally based drugs. As a result, docking studies were investigated for H2L ligand, [Mn(L)(H2O)2] and [Ni(L)(H2O)2] complexes with 5KBC, 3V7B and 4G9M receptors.

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“…Z.Y. Zhang et al have reported a l -Ornithine Schiff base-copper complex with proteasome-inhibitory activities and induction of apoptosis in MDA-MB-231 and LNCaP cancer cells.…”

mentioning

confidence: 99%

Novel Copper Complexes That Inhibit the Proteasome and Trigger Apoptosis in Triple-Negative Breast Cancer Cells

Yagüe

Wang

et al. 2019

ACS Med. Chem. Lett.

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Five innovative ternary copper(II) complexes [Cu(OH-PIP)(Phe)Cl](1), [Cu(OH-PIP)(Gly)(H 2 O)]NO 3 • 2H 2 O (2), [Cu(OH-PIP)(Ala)(Cl)]•H 2 O (3), [Cu(OH-PIP)(Met)]PF 6 •2H 2 O (4), and [Cu(OH-PIP)(Gln)(H 2 O)](Cl)• 3H 2 O (5) have been synthesized and characterized by infrared spectroscopy, elemental analysis, and single crystal X-ray diffraction analysis. X-ray crystallography indicates that all Cu atoms are five-coordinated in a square-pyramidal configuration. The complexes have been screened for cytotoxicity against human breast cancer cell lines MCF-7, MDA-MB-231, and CAL-51.The best anticancer activity is obtained with triple-negative breast cancer CAL-51 and MDA-MB-231 cell lines, with IC 50 values in the range of 0.082−0.69 μM. Importantly, the copper compounds were more effective than carboplatin at triggering cell death. Mechanistically, the complexes inhibit proteasomal chymotrypsin-like activity, and docking studies reveal their 20S proteasome binding sites. As a consequence, they cause the accumulation of ubiquitinated proteins, inhibit cell proliferation, and induce apoptosis. In addition, these copper complexes decrease the stemness of triple-negative breast cancer cells and have synergistic effects with CBP on TNBC cells, indicating their great potential as a novel therapy for triple-negative breast cancer.

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l-Ornithine Schiff base–copper and –cadmium complexes as new proteasome inhibitors and apoptosis inducers in human cancer cells

Cited by 23 publications

References 36 publications

Novel copper complexes as potential proteasome inhibitors for cancer treatment

Novel copper complexes as potential proteasome inhibitors for cancer treatment

Metal complexes of tetradentate azo‐dye ligand derived from 4,4′‐oxydianiline: Preparation, structural investigation, biological evaluation and MOE studies

Novel Copper Complexes That Inhibit the Proteasome and Trigger Apoptosis in Triple-Negative Breast Cancer Cells

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