Metal complexes against breast cancer stem cells

Li, Yingsi; Liu, Boxin; Shi, Hongdong; Wang, Yi; Sun, Qing; Zhang, Qianling

doi:10.1039/d1dt02909f

Cited by 43 publications

(39 citation statements)

References 120 publications

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“…Since the discovery of Cis platin, which greatly influenced the antitumor clinical practice, several other platinum-based metallodrugs have been designed and proved to possess a great effectiveness against several tumors [ 39 , 40 ]. However, these molecules exhibited, as well, a number of disadvantages and undesired effects in treated patients [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Au Carbene Complexes as Promising Multi-Target Agents in Breast Cancer Treatment

et al. 2022

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Over the past decade, metal complexes based on N-heterocyclic carbenes (NHCs) have attracted great attention due to their wide and exciting applications in material sciences and medicinal chemistry. In particular, the gold-based complexes are the focus of research efforts for the development of new anticancer compounds. Literature data and recent results, obtained by our research group, reported the design, the synthesis and the good anticancer activity of some silver and gold complexes with NHC ligands. In particular, some of these complexes were active towards some breast cancer cell lines. Considering this evidence, here we report some new Au-NHC complexes prepared in order to improve solubility and biological activity. Among them, the compounds 1 and 6 showed an interesting anticancer activity towards the breast cancer MDA-MB-231 and MCF-7 cell lines, respectively. In addition, in vitro and in silico studies demonstrated that they were able to inhibit the activity of the human topoisomerases I and II and the actin polymerization reaction. Moreover, a downregulation of vimentin expression and a reduced translocation of NF-kB into the nucleus was observed. The interference with these vital cell structures induced breast cancer cells’ death by triggering the extrinsic apoptotic pathway.

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Section: Discussionmentioning

confidence: 99%

Novel Au Carbene Complexes as Promising Multi-Target Agents in Breast Cancer Treatment

et al. 2022

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“…These unresolved issues call for novel therapeutic options and the use of alternative solutions, such as organometallic complexes of other platinum-group metals. There are numerous complexes of ruthenium [ 1 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ], osmium [ 2 , 9 , 12 , 13 , 14 , 15 , 16 , 17 ], rhodium [ 13 , 18 , 19 ], or iridium [ 2 , 12 , 13 , 18 , 20 ] that are used in oncological settings. In fact, one ruthenium complex, IT-139, has passed clinical phase-I studies and is intended for use in colorectal cancer [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…These particular modifications are summarized in target compounds VI–VIII in Figure 1 . Replacement of the central metal ion and the hexahapto-coordinating arene by an arenyl ligand may result in significant changes to the lipophilicity, membrane permeability and kinetic properties of the complexes; therefore, in the present study, we aimed to explore the effect of the use of other platinum-group metals (Os, Rh, Ir), having also proven their anticancer potential in the form of half-sandwich-type organometallic compounds [ 2 , 9 , 10 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. In addition, to investigate the effect of the important central heterocyclic moiety in the carbohydrate ligand, 1,2,4-oxadiazole derivatives were also included.…”

Section: Introductionmentioning

confidence: 99%

Reactive Oxygen Species Production Is Responsible for Antineoplastic Activity of Osmium, Ruthenium, Iridium and Rhodium Half-Sandwich Type Complexes with Bidentate Glycosyl Heterocyclic Ligands in Various Cancer Cell Models

Kacsir

Sipos

Bényei

et al. 2022

IJMS

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Platinum complexes are used in chemotherapy, primarily as antineoplastic agents. In this study, we assessed the cytotoxic and cytostatic properties of a set of osmium(II), ruthenium(II), iridium(III) and rhodium(III) half-sandwich-type complexes with bidentate monosaccharide ligands. We identified 5 compounds with moderate to negligible acute cytotoxicity but with potent long-term cytostatic activity. These structure-activity relationship studies revealed that: 1) osmium(II) p-cymene complexes were active in all models, while rhodium(III) and iridium(III) Cp* complexes proved largely inactive; 2) the biological effect was influenced by the nature of the central azole ring of the ligands—1,2,3-triazole was the most effective, followed by 1,3,4-oxadiazole, while the isomeric 1,2,4-oxadiazole abolished the cytostatic activity; 3) we found a correlation between the hydrophobic character of the complexes and their cytostatic activity: compounds with O-benzoyl protective groups on the carbohydrate moiety were active, compared to O-deprotected ones. The best compound, an osmium(II) complex, had an IC50 value of 0.70 µM. Furthermore, the steepness of the inhibitory curve of the active complexes suggested cooperative binding; cooperative molecules were better inhibitors than non-cooperative ones. The cytostatic activity of the active complexes was abolished by a lipid-soluble antioxidant, vitamin E, suggesting that oxidative stress plays a major role in the biological activity of the complexes. The complexes were active on ovarian cancer, pancreatic adenocarcinoma, osteosarcoma and Hodgkin’s lymphoma cells, but were inactive on primary, non-transformed human fibroblasts, indicating their applicability as potential anticancer agents.

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“…In fact, a ruthenium complex, IT-139 has passed clinical phase I to be applied in colorectal cancer ( Burris et al, 2016 ). Furthermore, rhodium ( Leung et al, 2013 ; Gichumbi and Friedrich, 2018 ; Štarha and Trávníček, 2019 ; Máliková et al, 2021 ), osmium ( Hartinger et al, 2011 ; Hanif et al, 2014 ; Gichumbi and Friedrich, 2018 ; Konkankit et al, 2018 ; Meier-Menches et al, 2018 ; Štarha and Trávníček, 2019 ; Nabiyeva et al, 2020 ; Li et al, 2021 ) and iridium ( Leung et al, 2013 ; Liu and Sadler, 2014 ; Gichumbi and Friedrich, 2018 ; Konkankit et al, 2018 ; Štarha and Trávníček, 2019 ; Li et al, 2021 ) compounds were also described as anticancer agent candidates.…”

Section: Introductionmentioning

confidence: 99%

Targeting Multiresistant Gram-Positive Bacteria by Ruthenium, Osmium, Iridium and Rhodium Half-Sandwich Type Complexes With Bidentate Monosaccharide Ligands

et al. 2022

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Bacterial resistance to antibiotics is an ever-growing problem in heathcare. We have previously identified a set of osmium(II), ruthenium(II), iridium(III) and rhodium(III) half-sandwich type complexes with bidentate monosaccharide ligands possessing cytostatic properties against carcinoma, lymphoma and sarcoma cells with low micromolar or submicromolar IC50 values. Importantly, these complexes were not active on primary, non-transformed cells. These complexes have now been assessed as to their antimicrobial properties and found to be potent inhibitors of the growth of reference strains of Staphylococcus aureus and Enterococcus faecalis (Gram-positive species), though the compounds proved inactive on reference strains of Pseudomonas aerugonisa, Escherichia coli, Candida albicans, Candida auris and Acinetobacter baumannii (Gram-negative species and fungi). Furthermore, clinical isolates of Staphylococcus aureus and Enterococcus sp. (both multiresistant and susceptible strains) were also susceptible to the organometallic complexes in this study with similar MIC values as the reference strains. Taken together, we identified a set of osmium(II), ruthenium(II), iridium(III) and rhodium(III) half-sandwich type antineoplastic organometallic complexes which also have antimicrobial activity among Gram-positive bacteria. These compounds represent a novel class of antimicrobial agents that are not detoxified by multiresistant bacteria suggesting a potential to be used to combat multiresistant infections.

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Metal complexes against breast cancer stem cells

Abstract: With the highest incidence, breast cancer ranks as the leading cause of cancer deaths among women in the world. Tumor metastasis and is the major contributor of high mortality in...

Cited by 43 publications

References 120 publications

Novel Au Carbene Complexes as Promising Multi-Target Agents in Breast Cancer Treatment

Novel Au Carbene Complexes as Promising Multi-Target Agents in Breast Cancer Treatment

Reactive Oxygen Species Production Is Responsible for Antineoplastic Activity of Osmium, Ruthenium, Iridium and Rhodium Half-Sandwich Type Complexes with Bidentate Glycosyl Heterocyclic Ligands in Various Cancer Cell Models

Targeting Multiresistant Gram-Positive Bacteria by Ruthenium, Osmium, Iridium and Rhodium Half-Sandwich Type Complexes With Bidentate Monosaccharide Ligands

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