Targeting Nucleus DNA with a Cyclometalated Dipyridophenazineruthenium(II) Complex

Huang, Huaiyi; Zhang, Pingyu; Yu, Baoxian; Chen, Yu; Wang, Jinquan; Ji, Liang‐Nian; Chao, Hui

doi:10.1021/jm501095r

Cited by 214 publications

(130 citation statements)

References 88 publications

(120 reference statements)

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“…Interestingly, the Ru(II) complexes 13s to 13x had lower IC 50 values against HeLa cells, resulting from an increase of the volume of the chelating ligands, which is partly due to the larger chelating ligands which produces higher cellular uptake and stronger interactions with DNA. 80,229,231 Recently, the same group also designed some cycloruthenated compounds with significant potency in hypoxic and cisplatin-resistant cancer cell lines. 232,233 Complex 13y - 5 (see Fig.…”

Section: Ruthenium(ii) Polypyridyl Complexesmentioning

confidence: 99%

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

et al. 2017

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Cancer is rapidly becoming the top killer in the world. Most of the FDA approved anticancer drugs are organic molecules, while metallodrugs are very scarce. The advent of first metal based therapeutic agent, cisplatin, launched a new era in the application of transition metal complexes for therapeutic design. Due to their unique and versatile biochemical properties, ruthenium-based compounds have emerged as promising anti-cancer agents that serve as alternatives to cisplatin and its derivertives. The ruthenium(III) complexes have successfully been used in clinical research and their mechanisms of anticancer action have been reported in large volumes over the past few decades. Ruthenium(II) complexes have also attracted significant attention as anticancer candidates; however, only few of them have been reported comprehensively. In this review, we discuss the development of ruthenium(II) complexes as anticancer candidates and biocatalysts, including arene ruthenium complexes, polypyridyl ruthenium complexes, and ruthenium nanomaterial complexes. This review focuses on the likely mechanisms of action of ruthenium(II)-based anticancer drugs and the relationship between their chemical structures and biological properties. This review also highlights the catalytic activity and the photoinduced activation of ruthenium(II) complexes, their targeted delivery, and their activity in nanomaterial systems.

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Section: Ruthenium(ii) Polypyridyl Complexesmentioning

confidence: 99%

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

et al. 2017

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“…[50][51][52][53] Recently, Ru(II) cyclometalated complexes have been also investigated as anticancer agents. [54][55][56][57] However, this topic together with the Ru(II) polypyridyl complexes activated by light or the non-coordinatively saturated Ru(II) polypyridyl complexes are not reviewed here. We send the interested readers to an excellent, very recent Review of Zeng and co-workers.…”

Section: Introductionmentioning

confidence: 99%

Monomeric and dimeric coordinatively saturated and substitutionally inert Ru(ii) polypyridyl complexes as anticancer drug candidates

2017

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Due to the increasing impact of cancer on worldwide mortality, more and more attention is being devoted to the investigation of novel anticancer strategies. Among these, chemotherapy plays a key role in fighting cancer. This explains the increasing engagement of both pharmaceutical industry and academia towards the discovery of new chemotherapeutic agents. Over the recent years, metal-based drugs have attracted much attention due to their atypical physico-chemical properties compared to organic molecules. After the approval of cisplatin as a chemotherapeutic agent in 1978, several types of metal-based drugs have been explored. Among them, Ru-based anticancer drug candidates have become a central subject in this research field. However, most of the Ru-based compounds investigated over the last two decades express their cytotoxicity with a mechanism of action involving, among others, a ligand-exchange mechanism. In this Review, we give a complete overview of a specific class of antiproliferative ruthenium complexes, namely coordinatively saturated and substitutionally inert Ru(II) polypyridyl complexes. This implies that the cytotoxicity observed comes from the entire complex and not from a ligand-exchange. In this Review, we are presenting monomeric and dimeric Ru(II) polypyridyl complexes, which have been found to be toxic to cancer cells. More specifically, the monomeric Ru(II) polypyridyl complexes are analysed considering their direct interaction or not with DNA as cause of cell death, while dimeric Ru(II) polypyridyl complexes, are classified according to their biological targets. Very importantly, the cellular targets of these complexes are discussed in detail. Indeed, several targets were identified and different mechanisms of action were suggested.

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“…11-16) Pfeffer and colleagues 17,18) and Chao and colleagues 19,20) have found that some cyclometalated ruthenium(II) complexes are good candidates for becoming anticancer drugs. A cyclometalated ruthenium fragment with a metal-carbon σ bond is a crucial element for a potential anticancer drug.…”

Section: )mentioning

confidence: 99%

“…[5][6][7][8][9][10] Several ruthenium complexes that display an activity comparable to that of cisplatin have been described, and in some cases activities are even better. [11][12][13][14][15][16] Pfeffer and colleagues 17,18) and Chao and colleagues 19,20) have found that some cyclometalated ruthenium(II) complexes are good candidates for becoming anticancer drugs. A cyclometalated ruthenium fragment with a metal-carbon σ bond is a crucial element for a potential anticancer drug.…”

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DNA Interaction and Cytotoxicity of Cyclometalated Ruthenium(II) Complexes as Potential Anticancer Drugs

Matsui

Sugiyama

Nakai

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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To evaluate the anticancer activity of the cyclometalated ruthenium(II) complexes [Ru(bpy) 2 (C^N)]Cl, we have studied the interaction of these complexes using calf thymus DNA (CT-DNA) and cytotoxicity assays with two tumor (L1210 and HeLa) and a non-tumor (BALB/3T3 clone A31) cell lines. It is suggested that the complexes act as intercalators and/or DNA minor groove binders. Moreover, the complexes display favorable cytotoxicity activities with L1210 and HeLa, which in all cases were significantly more favorable than cisplatin. In contrast, the complexes exhibit appreciably lower cytotoxicity toward BALB/3T3 clone A31.Key words cyclometalated ruthenium(II) complex; anticancer drug; cytotoxicity; oxidative DNA cleavage; lipophilicityThe discovery of cisplatin (cis-diamminedichloridoplatinum(II)) by Rosenberg was one of the most significant events for cancer chemotherapy.1) However, the use of cisplatin is restricted by its high toxicity, which leads to undesirable side effects and incidents of drug resistance. With the aim of overcoming these limitations, new platinum-based and non-platinum anticancer drugs are under development. A relatively new line of investigation focuses on ruthenium chemistry in an alternative metallopharmaceutical approach to platinum.2,3) The higher coordination number of ruthenium compared with platinum provides additional coordination sites, which can potentially be used to fine-tune the properties of the complex, for example, by influencing the way the complex interacts with DNA. 4)It is well accepted that ruthenium complexes can display anticancer effects with a fairly high selectivity, the lethality of the tumor cells being higher than that of the normal cells.5-10) Several ruthenium complexes that display an activity comparable to that of cisplatin have been described, and in some cases activities are even better.11-16) Pfeffer and colleagues 17,18) and Chao and colleagues 19,20) have found that some cyclometalated ruthenium(II) complexes are good candidates for becoming anticancer drugs. A cyclometalated ruthenium fragment with a metal-carbon σ bond is a crucial element for a potential anticancer drug. The ruthenium-carbon bond is known to lower the redox potential of ruthenium(III/II) couple dramatically, so that cyclometalated ruthenium(II) complexes may serve as good catalysts for the generation of hydroxyl radicals by virtue of the Fenton-like reaction. In addition, they have good lipophilicity that allows their entries into the cells. 18,20) From two features these cyclometalated ruthenium(II) complexes may lead to excellent anticancer drugs because many cancer cells possess low levels of catalase activity. 21)In the present study, we have synthesized the cyclometalated ruthenium(II) complexes as shown in Fig. 1, [Ru(bpy) 2 (C^N)] Cl, where bpy is 2,2′-bipyridine and C^N is the deprotonated cyclometalating ligand (2-phenylpyridine (phpy), 2-(4-methylphenyl) pyridine (mphpy), or diphenyldiazene (dphdaz)). To evaluate the anticancer activity of these complexes physicochemical p...

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Targeting Nucleus DNA with a Cyclometalated Dipyridophenazineruthenium(II) Complex

Cited by 214 publications

References 88 publications

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

Monomeric and dimeric coordinatively saturated and substitutionally inert Ru(ii) polypyridyl complexes as anticancer drug candidates

DNA Interaction and Cytotoxicity of Cyclometalated Ruthenium(II) Complexes as Potential Anticancer Drugs

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