Ruthenium(<scp>ii</scp>)–arene complexes as anti-metastatic agents, and related techniques

Sonkar, Chanchal; Sarkar, Sayantan; Mukhopadhyay, Suman

doi:10.1039/d1md00220a

Cited by 31 publications

(27 citation statements)

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“…Ruthenium-containing compounds are the most promising non-platinum candidates for metal-based cancer therapy due to their suitable features for anticancer drug design, such as the ability to strongly bind nucleic acids and proteins [ 160 ], ligand exchange kinetics similar to platinum compounds [ 161 ], preferential accumulation in neoplastic tissues [ 162 ], the possibility of photodynamic approaches to therapy [ 163 , 164 ], ability to mimic iron binding in biological systems [ 165 ], and lower toxicity than platinum compounds [ 166 ]. Indeed, four ruthenium coordination compounds [ 167 , 168 , 169 , 170 ] ( Figure 5 A) and three organoruthenium compounds [ 171 , 172 ] ( Figure 5 B) have reached the stage of clinical evaluation in humans for cancer treatment.…”

Section: Non-platinum-containing Metal Therapeutic Agents Loaded Into...mentioning

confidence: 99%

Polymeric Nanosystems Applied for Metal-Based Drugs and Photosensitizers Delivery: The State of the Art and Recent Advancements

2022

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Nanotechnology-based approaches for targeting the delivery and controlled release of metal-based therapeutic agents have revealed significant potential as tools for enhancing the therapeutic effect of metal-based agents and minimizing their systemic toxicities. In this context, a series of polymer-based nanosized systems designed to physically load or covalently conjugate metal-based therapeutic agents have been remarkably improving their bioavailability and anticancer efficacy. Initially, the polymeric nanocarriers were applied for platinum-based chemotherapeutic agents resulting in some nanoformulations currently in clinical tests and even in medical applications. At present, these nanoassemblies have been slowly expanding for nonplatinum-containing metal-based chemotherapeutic agents. Interestingly, for metal-based photosensitizers (PS) applied in photodynamic therapy (PDT), especially for cancer treatment, strategies employing polymeric nanocarriers have been investigated for almost 30 years. In this review, we address the polymeric nanocarrier-assisted metal-based therapeutics agent delivery systems with a specific focus on non-platinum systems; we explore some biological and physicochemical aspects of the polymer–metallodrug assembly. Finally, we summarize some recent advances in polymeric nanosystems coupled with metal-based compounds that present potential for successful clinical applications as chemotherapeutic or photosensitizing agents. We hope this review can provide a fertile ground for the innovative design of polymeric nanosystems for targeting the delivery and controlled release of metal-containing therapeutic agents.

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Section: Non-platinum-containing Metal Therapeutic Agents Loaded Into...mentioning

confidence: 99%

Polymeric Nanosystems Applied for Metal-Based Drugs and Photosensitizers Delivery: The State of the Art and Recent Advancements

2022

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“…When appropriate plasma levels were reached, ( 6) was able to achieve clinical activity against various tumour types. The sodium salt of ( 6), which is KP1339 is also under clinical trials (Sonkar et al, 2021). The ruthenium(III) complex, IT-139 (8) (Figure 2) has been used to treat cancer cells by targeting metastatic development in cancer patients (Lizardo et al, 2016), which was very effective in combination treatments and also as a single agent for carcinoid neuroendocrine tumours and colorectal cancer (Trondl et al, 2014).…”

Section: Indazole-based Kp1019 Kp1339 and It-139 As Anticancer Agentsmentioning

confidence: 99%

“…These complexes showed significant anticancer properties in vitro, and cytotoxicity against human ovarian cancer cells (Pettinari et al, 2013). The (arene)Ru(II) complex [(cymene)RuCl(picolinate)] (37) bound efficiently to DNA and showed antimetastatic activity and antiproliferative activity, despite its low level of genotoxicity and cytotoxicity (Sonkar et al, 2021). With NHC as a N^C donor ligand Cationic (arene)Ru(II) complexes (38a-f) (Figure 15) with benzothiazole-functionalized NHC ligand (NHC = nitrogenheterocarbene) were studied for their cytotoxic activity.…”

Section: With β-Ketoamine As a N^o Donor Ligandmentioning

confidence: 99%

Development of Mononuclear (Arene) Ruthenium Complexes as Anticancer Agents: A Review

Amarasinghe

Perera

2022

OUSL Jnl

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Arene)ruthenium complexes have displayed promising activity against cancer and showed fewer side effects compared to platinum-based drugs. Activity tuning of arene complexes have been explored by varying, amines, phosphines and other N^N, N^O, N^S, N^C, S^O chelating ligands. (Arene)Ru(II) complexes, where arene = cymene (C), benzene (B), toluene (T), hexamethylbenzene (H); L = amine, phosphine; L^L = en, diamine, diphosphine, (X^Y) = oxalate, (L^X) = acylacetonate; and (X), (Y) = halides, triflates etc. exhibit a high structural variety, and offer much potential in drug design. In this review, an overview of the progress in the field of mononuclear ruthenium complexes containing arenes and other co-ligands such as, PTA (1,3,5-triaza-7-phosphaadamantane), ethylenediamine (en), phosphines, thiosemicarbazone, acylthiourea and their bioactivity is presented.

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“…In these complexes, 1,3,5-triaza-7-phosphaadamantane (PTA) or its derivatives are used as monodentate ligands, having a phosphorous donor atom. The most studied half-sandwich complexes have the general structure [M(arene)(X,Y)(Z)], in which M is a platinum group metal ion: (Ru(II), Os(II), Rh(III), and Ir(III)); arene is a neutral benzene derivative (mostly for Ru(II) and Os(II)) or pentamethylcyclopentadienyl anion (Cp*) derivative (mostly for Rh(III) and Ir(III)); (X,Y) is a bidentate ligand, and Z is a monodentate ligand, usually having a role in the leaving group (halide ion or H 2 O) [ 13 , 14 , 15 , 16 ]. Among these compounds, RAED (ruthenium arene ethylenediamine) complexes, bearing ethylenediamine (en) as bidentate (N,N) donor ligand, showed excellent cytotoxicity in vitro (IC 50 ≤ 10 μM) [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Half-Sandwich Rhodium Complexes with Releasable N-Donor Monodentate Ligands: Solution Chemical Properties and the Possibility for Acidosis Activation

et al. 2023

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Cancer chemotherapeutics usually have serious side effects. Targeting the special properties of cancer and activation of the anticancer drug in the tumor microenvironment in situ may decrease the intensity of the side effects and improve the efficacy of therapy. In this study, half-sandwich Rh complexes are introduced, which may be activated at the acidic, extracellular pH of the tumor tissue. The synthesis and aqueous stability of mixed-ligand complexes with a general formula of [Rh(η5-Cp*)(N,N/O)(N)]2+/+ are reported, where (N,N/O) indicates bidentate 8-quinolate, ethylenediamine and 1,10-phenanthroline and (N) represents the releasable monodentate ligand with a nitrogen donor atom. UV-visible spectrophotometry, 1H NMR, and pH-potentiometry were used to determine the protonation constants of the monodentate ligands, the proton dissociation constants of the coordinated water molecules in the aqua complexes, and the formation constants of the mixed-ligand complexes. The obtained data were compared to those of the analogous Ru(η6-p-cymene) complexes. The developed mixed-ligand complexes were tested in drug-sensitive and resistant colon cancer cell lines (Colo205 and Colo320, respectively) and in four bacterial strains (Gram-positive and Gram-negative, drug-sensitive, and resistant) at different pH values (5–8). The mixed-ligand complexes with 1-methylimidazole displayed sufficient stability at pH 7.4, and their activation was found in cancer cells with decreasing pH; moreover, the mixed-ligand complexes demonstrated antimicrobial activity in Gram-positive and Gram-negative bacteria, including the resistant MRSA strain. This study proved the viability of incorporating releasable monodentate ligands into mixed-ligand half-sandwich complexes, which is supported by the biological assays.

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Ruthenium(ii)–arene complexes as anti-metastatic agents, and related techniques

Abstract: Owing to the discovery of cisplatin, a vast area of use of metallodrugs in cancer treatment was opened, but due to the side effects caused by the cisplatin complexes, researchers...

Cited by 31 publications

References 146 publications

Polymeric Nanosystems Applied for Metal-Based Drugs and Photosensitizers Delivery: The State of the Art and Recent Advancements

Polymeric Nanosystems Applied for Metal-Based Drugs and Photosensitizers Delivery: The State of the Art and Recent Advancements

Development of Mononuclear (Arene) Ruthenium Complexes as Anticancer Agents: A Review

Half-Sandwich Rhodium Complexes with Releasable N-Donor Monodentate Ligands: Solution Chemical Properties and the Possibility for Acidosis Activation

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