Unexplored features of Ru(<scp>ii</scp>) polypyridyl complexes – towards combined cytotoxic and antimetastatic activity

Gurgul, Ilona; Mazuryk, Olga; Łomzik, Michał; Rutkowska‐Zbik, Dorota; Brindell, Małgorzata

doi:10.1039/d0mt00019a

Cited by 20 publications

(30 citation statements)

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“…The detailed mechanism of such activity is still largely unknown; however, some of these compounds have been shown to strongly alter cell adhesion properties. MMP-2 and MMP-9 were considered among the postulated targets, and it was shown that some of the ruthenium polypyridyl complexes may inhibit their activity [19], while others may down-regulate their secretion [14,16]. In this study, for the first time, we investigate the relationship between the localization of Ru in the cell and the expression level of MMPs by analyzing subcellular fractions, which may strengthen the hypothesis of MMPs as potential targets for Ru polypyridyl complexes.…”

Section: Introductionmentioning

confidence: 71%

“…Ruthenium polypyridyl complexes have been tested for many years for their use in anticancer therapy as cytotoxic agents [10][11][12]. Recently, ours and other studies have shown that ruthenium polypyridyl compounds in addition to their well-documented cytotoxic activity can affect various cell properties such as detachment, motility, invasion, colonization ability, and others that are crucial for metastasis formation and development [13][14][15][16][17][18][19]. The detailed mechanism of such activity is still largely unknown; however, some of these compounds have been shown to strongly alter cell adhesion properties.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Matrix Metalloproteinases and Cancer Cell Detachment by Ru(II) Polypyridyl Complexes Containing 4,7-Diphenyl-1,10-phenanthroline Ligands—New Candidates for Antimetastatic Agents

et al. 2021

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Primary tumor targeting is the dominant approach in drug development, while metastasis is the leading cause of cancer death. Therefore, in addition to the cytotoxic activity of a series of Ru(II) polypyridyl complexes of the type [Ru(dip)2L]2+ (dip: 4,7-diphenyl-1,10-phenanthroline while L = dip; bpy: 2,2′-bipyridine; bpy-SC: bipyridine derivative bearing a semicarbazone 2-formylopyridine moiety; dpq, dpq(CH3)2, dpb: quinoxaline derivatives) their ability to inhibit cell detachment was investigated. In vitro studies performed on lung cancer A549 cells showed that they accumulate in cells very well and exhibit moderate cytotoxicity with IC50 ranging from 4 to 13 µM. Three of the studied compounds that have dip, bpy-SC, or dpb ligands after treatment of the cells with a non-toxic dose (<1/2IC50) enhanced their adhesion properties demonstrated by lower detachment in the trypsin resistance assay. The same complexes inhibited both MMP-2 and MMP-9 enzyme activities with IC50 ranging from 2 to 12 µM; however, the MMP-9 inhibition was stronger. More detailed studies for [Ru(dip)2(bpy-SC)]2+, which induced the greatest increase in cell adhesion, revealed that it is predominately accumulated in the cytoskeletal fraction of A549 cells. Moreover, cells treated with this compound showed the localization of MMP-9 to a greater extent also in the cytoskeleton. Taken together, our results indicate the possibility of a reduction of metastatic cells escaping from the primary lesion to the surrounding tissue by prevention of their detachment and by influencing the activity of MMP-2 and MMP-9.

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Section: Introductionmentioning

confidence: 71%

Section: Introductionmentioning

confidence: 99%

Inhibition of Matrix Metalloproteinases and Cancer Cell Detachment by Ru(II) Polypyridyl Complexes Containing 4,7-Diphenyl-1,10-phenanthroline Ligands—New Candidates for Antimetastatic Agents

et al. 2021

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“…Ru(II) compounds can not only suppress the primary tumor but also effectively inhibit malignant tumor metastasis. A series of recently synthesized Ru(II)-containing polypyridyl ligand complexes (Ru25-29 (Figure 6) [53] and Ru47 (Figure 9) [61]) showed…”

Section: Anti-metastasismentioning

confidence: 99%

“…A series of recently synthesized Ru(II)-containing polypyridyl ligand complexes ( Ru25–29 ( Figure 6 ) [ 53 ] and Ru47 ( Figure 9 ) [ 61 ]) showed anti-metastatic properties, which was attributed to their targeting ability to MMPs [ 53 ]. Ru25–29 bearing 2,2′-bipyridine substituted with a semicarbazone-2-formylopyridine moiety as one of the ligands and 4,4′-di-tert-butyl-2,2′-dipyridyl or 4,7-diphenyl-1,10-phenanthroline as auxiliary ligands have been studied for their effect on the adhesion properties of human A549 and pancreatic cancer cells [ 53 ]. All complexes enhanced the cell adherent properties and could directly inhibit the activity of MMP2 and MMP9 enzymes in vitro.…”

Section: Ru(ii) Complexesmentioning

confidence: 99%

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Ruthenium Complexes as Promising Candidates against Lung Cancer

Sun

Shi

et al. 2021

Molecules

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Lung cancer is one of the most common malignancies with the highest mortality rate and the second-highest incidence rate after breast cancer, posing a serious threat to human health. The accidental discovery of the antitumor properties of cisplatin in the early 1960s aroused a growing interest in metal-based compounds for cancer treatment. However, the clinical application of cisplatin is limited by serious side effects and drug resistance. Therefore, other transition metal complexes have been developed for the treatment of different malignant cancers. Among them, Ru(II/III)-based complexes have emerged as promising anticancer drug candidates due to their potential anticancer properties and selective cytotoxic activity. In this review, we summarized the latest developments of Ru(II/III) complexes against lung cancer, focusing mainly on the mechanisms of their biological activities, including induction of apoptosis, necroptosis, autophagy, cell cycle arrest, inhibition of cell proliferation, and invasion and metastasis of lung cancer cells.

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Ruthenium(II) Polypyridyl Complexes Containing Simple Dioxo Ligands: a Structure‐Activity Relationship Study Shows the Importance of the Charge

et al. 2022

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Cancer is one of the main causes of death worldwide. Platinum complexes (i. e., cisplatin, carboplatin, and others) are currently heavily used for the treatment of different types of cancer, but unwanted effects occur. Ruthenium complexes have been shown to be potential promising alternatives to these metalbased drugs. In this work, we performed a structure-activity relationship (SAR) study on two small series of Ru(II) polypyridyl complexes of the type [Ru(L1) 2 (O^O)]Cl n (3-8), where L1 is 4,7diphenyl-1,10-phenantroline (DIP) or 1,10-phenantroline (phen), and O^O is a symmetrical anionic dioxo ligand: oxalate (ox, n = 0), malonate (mal, n = 0), or acetylacetonate (acac, n = 1). These two self-consistent series of compounds allowed us to perform a systematic investigation for establishing how the nature of the ligands and the charge affect the anticancer properties of the complexes. Cytotoxicity tests on different cell lines demonstrated that some of the six compounds 3-8 have a promising anticancer activity. More specifically, the cationic complex [Ru(DIP) 2 (η 2 -acac)]Cl (4) has IC 50 values in the mid-nanomolar concentration range, lower than those of cisplatin on the same cell lines. Interestingly, [Ru(DIP) 2 (η 2 -acac)]Cl was found to localize mainly in the mitochondria, whereas a smaller fraction was detected in the nucleus. Overall, our SAR investigation demonstrates the importance of combining the positive charge of the complex with the highly lipophilic diimine ligand DIP.

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Unexplored features of Ru(ii) polypyridyl complexes – towards combined cytotoxic and antimetastatic activity

Abstract: Promising antimetastatic compounds having high cytotoxicity against cancer cells combined with strong influence on their adhesion properties as well as inhibition of their metalloproteinases.

Cited by 20 publications

References 31 publications

Inhibition of Matrix Metalloproteinases and Cancer Cell Detachment by Ru(II) Polypyridyl Complexes Containing 4,7-Diphenyl-1,10-phenanthroline Ligands—New Candidates for Antimetastatic Agents

Inhibition of Matrix Metalloproteinases and Cancer Cell Detachment by Ru(II) Polypyridyl Complexes Containing 4,7-Diphenyl-1,10-phenanthroline Ligands—New Candidates for Antimetastatic Agents

Ruthenium Complexes as Promising Candidates against Lung Cancer

Ruthenium(II) Polypyridyl Complexes Containing Simple Dioxo Ligands: a Structure‐Activity Relationship Study Shows the Importance of the Charge

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