Effect of cysteine thiols on the catalytic and anticancer activity of Ru(<scp>ii</scp>) sulfonyl-ethylenediamine complexes

Chen, Feng; Romero‐Canelón, Isolda; Habtemariam, Abraha; Song, Ji‐Inn; Banerjee, Samya; Clarkson, Guy J.; Song, Lijiang; Prokeš, Ivan; Sadler, Peter J.

doi:10.1039/d1dt03856g

Cited by 10 publications

(9 citation statements)

References 59 publications

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“…The synthesis of Ru1 – Ru3 and their characterization, including 1 H NMR (Figure S1), 13 C NMR, ESI-MS, and microanalysis, are shown in the Supporting Information. In comparison to Cl-coordinated Ru(II)-arene complexes, coordination-saturated PRCs are known to be inert to ligand substitution. , By examining the absorption spectral changes of Ru(II) complexes in the absence of light, no hydrolysis was observed for Ru1 – Ru3 in the aqueous solution (Tris–HCl buffer, Figure S2) or RPMI 1640 cell culture medium (Figure S3). Upon light irradiation with a 450 nm LED (50 mW cm –2 ) or an 808 nm LPL (100 mW cm –2 ), Ru1 – Ru3 are also stable, as the spectra showed nearly no change in the MLCT bands.…”

Section: Resultsmentioning

confidence: 99%

More-Is-Better Strategy for Constructing Homoligand Polypyridyl Ruthenium Complexes as Photosensitizers for Infrared Two-Photon Photodynamic Therapy

Tang,

Wang,

Yang

et al. 2023

Inorg. Chem.

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Photodynamic therapy (PDT) uses a combination of photosensitizers (PSs), light sources, and reactive oxygen species (ROS) to damage only the desired target and keep normal tissues from being hurt. The dark cytotoxicity (chemotoxicity) of PSs, leading to whole-body damage in the absence of irradiation, is a major limiting factor in PDT. How to simultaneously increase ROS generation and decrease dark cytotoxicity is an essential challenge that must be resolved in PS research. In this study, a series of homoligand polypyridyl ruthenium complexes (HPRCs) containing three singlet oxygen ( 1 O 2 )-generating ligands (L) in a single molecule ([Ru(L) 3 ] 2+ ) have been constructed. Compared to the heteroligand complexes [Ru(bpy) 2 (L)] 2+ where bpy is 2,2′-bipyridine, the 1 O 2 quantum yield under infrared two-photon irradiation and the DNA photocleavage effect of the HPRCs are significantly enhanced with two more ligands L. The intraligand triplet excited states transition played an important role in the activation of oxygen. The HPRCs target the mitochondria but not the nuclei, generating 1 O 2 intracellularly under irradiation of visible or infrared light. Ru1 exhibits high phototoxicity and low dark cytotoxicity toward human malignant melanoma cells in vitro. Moreover, HPRCs have minimal cytotoxicity to human normal liver cells, suggesting their potential as antitumor PDT reagents with more security. This study may provide inspiration for the structural design of potent PS for PDT.

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Section: Resultsmentioning

confidence: 99%

More-Is-Better Strategy for Constructing Homoligand Polypyridyl Ruthenium Complexes as Photosensitizers for Infrared Two-Photon Photodynamic Therapy

Tang,

Wang,

Yang

et al. 2023

Inorg. Chem.

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“…Furthermore, the cysteine moiety was coupled to some of the compounds to actively contribute to cancer metabolic remodeling through redox control and to enhance the antioxidant effect of the synthesized structure. 54,55 The synthesis strategy to form the final products involved Grignard reagents and BF3 reagents as an alkylating agent and as Lewis acid aiding the coupling of cysteine agents, respectively. The products were purified using solvent systems (n-hexane/ethyl acetate).…”

Section: Resultsmentioning

confidence: 99%

“…The rings were incorporated as they were proposed to enhance the interaction pattern in terms of hydrophobic and π–π interactions. Furthermore, the cysteine moiety was coupled to some of the compounds to actively contribute to cancer metabolic remodeling through redox control and to enhance the antioxidant effect of the synthesized structure. , …”

Section: Resultsmentioning

confidence: 99%

Biological Evaluation of Xanthene and Thioxanthene Derivatives as Antioxidant, Anticancer, and COX Inhibitors

Abualhasan,

Hawash,

Aqel

et al. 2023

ACS Omega

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Xanthene and thioxanthene analogues have been investigated for their potential as anticancer and anti-inflammatory agents. Additionally, cysteine analogues have been found to possess antioxidant, anti-inflammatory, and anticancer activities due to their role in cellular redox balance, scavenging of free radicals, and involvement in nucleophilic reactions and enzyme binding sites. In this study, we synthesized a library of tertiary alcohols derived from xanthene and thioxanthene, and further, some of these compounds were coupled with cysteine. The objective of this research was to explore the potential anticancer, antioxidant, and anti-inflammatory activities of the synthesized compounds. The synthesized compounds were subjected to test for anticancer, antioxidant, and anti-inflammatory activities. Results indicated that compound 3 exhibited excellent inhibition activity (IC50 = 9.6 ± 1.1 nM) against colon cancer cells (Caco-2), while compound 2 showed good inhibition activity (IC50 = 161.3 ± 41 nM) against hepatocellular carcinoma (Hep G2) cells. Compound 4 demonstrated potent antioxidant inhibition activity (IC50 = 15.44 ± 6 nM), and compound 7 exhibited potent anti-inflammatory activity with cyclooxygenase-2 (COX-2) inhibition IC50 (4.37 ± 0.78 nM) and high selectivity for COX-2 (3.83). In conclusion, certain synthesized compounds displayed promising anticancer activity and anti-inflammatory effects. Nevertheless, additional research is necessary to create more analogues, develop a more distinct comprehension of the structure–activity relationship (SAR), and perform in vivo experiments to evaluate the pharmacokinetic and pharmacodynamic characteristics of the compounds under examination. Such research may pave the way for the development of novel therapeutic agents with potential applications in cancer and inflammatory diseases.

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“…Despite the excellent potential of (arene)Ru complexes as anticancer agents, none of them has entered clinical trials so far, probably due to their uncertain mechanism of action . Interestingly, some half-sandwich Ru complexes were shown to exhibit anticancer properties due to their catalytic transfer hydrogenation activity in the reduction of NAD + to NADH. − Other half-sandwich Ru complexes could bypass multidrug resistance and conventional programmed cell death pathways induced by commonly used chemotherapeutic agents. , Therefore, this class of compounds still remains worthy of investigation.…”

Section: Introductionmentioning

confidence: 99%

Coordination of Ru(II)-Arene Fragments to Dipyridophenazine Ligands Leads to the Modulation of Their In Vitro and In Vivo Anticancer Activity

Nikolić,

Arakelyan,

Kushnarev

et al. 2023

Inorg. Chem.

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Despite extensive research on the anticancer properties of Ru complexes with dipyrido[3,2-a:2′,3′-c]phenazine (dppz) ligands, their in vivo efficacy is rarely investigated. Aiming to understand whether the coordination of certain half-sandwich Ru(II)-arene fragments might improve the therapeutic potential of dppz ligands, we prepared a series of Ru(II)-arene complexes with the general formula [(η 6 -arene)Ru(dppz-R)Cl]PF 6 , where the arene fragment was benzene, toluene, or p-cymene and R was -NO 2 , -Me, or -COOMe. All compounds were fully characterized by 1 H and 13 C NMR spectroscopy and highresolution ESI mass-spectrometry, and their purity was verified by elemental analysis. The electrochemical activity was investigated using cyclic voltammetry. The anticancer activity of dppz ligands and their respective Ru complexes was assessed against several cancer cell lines, and their selectivity toward cancer cells was assessed using healthy MRC5 lung fibroblasts. The substitution of benzene with a p-cymene fragment resulted in a more than 17-fold increase of anticancer activity and selectivity of Ru complexes and significantly enhanced DNA degradation in HCT116 cells. All Ru complexes were electrochemically active in the biologically accessible redox window and were shown to markedly induce the production of ROS in mitochondria. The lead Ru-dppz complex significantly reduced tumor burden in mice with colorectal cancers without inducing liver and kidney toxicity.

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Effect of cysteine thiols on the catalytic and anticancer activity of Ru(ii) sulfonyl-ethylenediamine complexes

Abstract: Sulfonyl ethylenediamine Ru(ii) arene transfer hydrogenation catalysts can have high anticancer activity, but react rapidly with thiols, forming bridged dinuclear complexes.

Cited by 10 publications

References 59 publications

More-Is-Better Strategy for Constructing Homoligand Polypyridyl Ruthenium Complexes as Photosensitizers for Infrared Two-Photon Photodynamic Therapy

More-Is-Better Strategy for Constructing Homoligand Polypyridyl Ruthenium Complexes as Photosensitizers for Infrared Two-Photon Photodynamic Therapy

Biological Evaluation of Xanthene and Thioxanthene Derivatives as Antioxidant, Anticancer, and COX Inhibitors

Coordination of Ru(II)-Arene Fragments to Dipyridophenazine Ligands Leads to the Modulation of Their In Vitro and In Vivo Anticancer Activity

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