📋 Browse Articles

Subtle ligand modifications on Ru^II -polypyridyl complexes may result in different excited-state characteristics, which provides the opportunity to tune their photo-physicochemical properties and subsequently change their biological functions. Here, a DNA-targeting Ru^II -polypyridyl complex (named Ru1) with highly photosensitizing ³ IL (intraligand) excited state was designed based on a classical DNA-intercalator [Ru(bpy)₂ (dppz)]⋅2 PF₆ by incorporation of the dppz (dipyrido[3,2-a:2',3'-c]phenazine) ligand tethered with a pyrenyl group, which has four orders of magnitude higher potency than the model complex [Ru(bpy)₂ (dppz)]⋅2 PF₆ upon light irradiation. This study provides a facile strategy for the design of organelle-targeting Ru^II -polypyridyl complexes with dramatically improved photobiological activity. Show less

Herein, we describe a new family of tris chelate homoleptic Ru (II) complexes, [Ru(N^N)3]2+, where the role of the diimine‐type ligands (N^N) was fulfilled by 2‐pyridyl (PTZ) or 2‐quinolyl tetrazole (QTZ) derivatives decorated with various alkyl substituents at the N‐2 position of the tetrazole ring. The new Ru (II) complexes with general formula [Ru (PTZ‐R)3]2+ and [Ru (QTZ‐R)3]2+, were obtained as mixtures of facial (fac) and meridional (mer) isomers, as suggested by NMR (1H, 13C) experiments, and confirmed in the case of mer‐[Ru (QTZ‐Me)3]2+, by X‐ray crystallography. The photophysical behavior of the tetrazole‐based [Ru(N^N)3]2+ type species was investigated by UV–vis absorption spectroscopy, providing trends typical of polypyridyl Ru (II) complexes. The new homoleptic complexes fac/mer‐[Ru (PTZ‐R)3]2+ and fac/mer‐[Ru (QTZ‐R)3]2+ have been assessed for any eventual antimicrobial activity towards two different bacteria such as Gram‐negative Escherichia coli and Gram‐positive Deinococcus radiodurans. Whereas being inactive toward E. coli, the response of agar disks diffusion tests suggested that some of the new fac/mer Ru (II) complexes could inhibit the growth of D. radiodurans. This effect was further investigated by determining the growth kinetics in liquid medium of D. radiodurans exposed to the fac/mer‐[Ru (PTZ‐R)3]2+ and fac/mer‐[Ru (QTZ‐R)3]2+ complexes at different concentrations. The outcome of these experiments highlighted that the turn‐on of the growth inhibitory effect took place as the linear hexyl chain was appended to the PTZ or QTZ scaffold, suggesting also how the inhibitory activity appeared more pronouncedly exerted by the facial isomers fac‐[Ru (PTZ‐Hex)3]2+ and fac‐[Ru (QTZ‐Hex)3]2+ (MIC = ca. 3.0 μg/ml) with respect to the corresponding meridional isomers (MIC = ca. 6.0 μg/ml). Show less

A series of ruthenium(II)-arene complexes of several bipyridine and phenanthroline derivatives have been synthesized by employing a green and efficient protocol involving water as a solvent under sonication. The structures of all the complexes were elucidated by the spectroscopic analysis. The geometry of the chlorido and PTA (1,3,5-Triaza-7-phosphaadamantane) complexes were further confirmed by DFT and single crystal XRD. The stability study in various solvents, specifically in the intracellular one was conducted. Most of the compounds exhibited significant potency and selectivity against MCF7 and HeLa cell lines with respect to normal HEK-293 cells compared to cisplatin and RAPTA-C (Ruthenium(II)-arene PTA complex). Complex [(η6-hexamethylbenzene)RuCl(κ2-N,N-4,4'-di-n-nonyl-2,2'-bpy)]Cl (3e) presented best anticancer profiles against all the human cancer cells. Interestingly, few complexes turned up to be highly fluorescent depicted by the quantum yield values. Remarkably, [(η6-p-cymene)RuCl(κ2-N,N-bpy)]Cl (3i) was identified as most significant anticancer theranostic agent interms of potency, selectivity and fluorescence quantum yield. This complex also represented itself as significant cellular imaging agent in live U-87 MG cells which was monitored by confocal microscope. Absorption and emission spectral studies of bypyridine and phenanthroline complex series revealed that the complexes interacted with calf thymus DNA through groove binding as well as intercalative mode. In addition to this, strong binding efficacy of these scaffolds wih BSA (Bovin Serum Albumin) also enhanced their transportation property inside the cells. Show less

Herein the design and synthesis of a new 8-hydroxyquinoline derivative, (S)-5-chloro-7-((proline-1-yl)methyl)8-hydroxyquinoline (HQCl-Pro), with good water solubility and multidrug resistance reversal activity are reported. In this work the proton dissociation processes of HQCl-Pro and its complex formation with [Rh(η⁵-C₅Me₅)(H₂O)₃]²⁺, [Ru(η⁶-p-cymene)(H₂O)₃]²⁺ and [Ru(η⁶-toluene)(H₂O)₃]²⁺ were investigated by the combined use of pH-potentiometry, UV-visible spectrometry and ¹H NMR spectroscopy. Our results revealed the prominent solution stability of the complexes in all cases. The lipophilicity of the complexes increased with the chloride ion concentration, and the complexes showed moderate log D values (-0.8 to +0.4) at pH 7.4 at all tested Cl^- concentrations. The formation of mixed hydroxido complexes from the aqua complexes was characterized by relatively high pK_a values (8.45-9.62 in chloride-free medium). Complexation processes are much slower with the Ru(η⁶-arene) triaqua cations than with [Rh(η⁵-C₅Me₅)(H₂O)₃]²⁺. Both the pK_a values and H₂O/Cl^- exchange constants of the Ru-complexes are lower by 0.5-1.0 orders of magnitude than those of the Rh analogue. Arene loss (p-cymene and toluene) and oxidation were found in the case of Ru-complexes when an excess of HQCl-Pro and aromatic (N,N) bidentate ligands was added. The cytotoxicity and antiproliferative effect of HQCl-Pro and its complexes were assayed in vitro. In contrast to the structurally familiar 8-hydroxyquinoline, HQCl-Pro and its Rh(η⁵-C₅Me₅) complex were somewhat more effective against drug resistant Colo 320 adenocarcinoma human cells compared to the drug sensitive Colo 205 cells. The Ru- and Rh-complexes showed a similar metal uptake level after 4 h, while a longer incubation time resulted in higher cellular Rh concentration. Show less

Ruthenium(ii) diclofenac-based complexes of the general formula [Ru(dicl)(P-P)(bpy)]PF6 [dicl = diclofenac, bpy = 2,2'-bipyridine, and P-P = 1,4'-bis(diphenylphosphino)butane (dppb) (1), 1,2'-bis(diphenylphosphino)ethane (dppe) (2), 1,3'-bis(diphenylphosphino)propane (dppp) (3) and 1,1'-bis(diphenylphosphino)ferrocene (dppf) (4)] are synthesized. The complexes (1-4) are characterized by elemental analyses, infrared, NMR, and UV-vis spectroscopy and (3) and (4) are characterized by single crystal X-ray diffraction. The DNA binding of complexes (1-4), studied by circular dichroism (CD) and Hoechst 33 258 staining assay, indicates their binding with the minor grooves. The complexes interact with BSA with binding constants (Kb) in the range of 2.5 × 103-5.5 × 104 M-1. The complexes exhibit high cytotoxicity against the tumor cell lines A549, MDA-MB-231, and MCF-7 with IC50 values ranging from 0.56 to 15.28 μM. The complexes are more selective for the hormone-dependent MCF-7 breast tumor cell line and complex (1) is the most potent one. The study demonstrates the anticancer activity of ruthenium(ii)/diclofenac-based complexes. Show less

Cardiolipins (CLs) are specific phospholipids of the mitochondria composing about 20% of the inner mitochondria membrane (IMM) phospholipid mass. Dysregulation of CL metabolism has been observed in several types of cancer. In most cases, the evidence for a role for CL in cancer is merely correlative, suggestive, ambiguous, and cancer-type dependent. In addition, CLs could play a pivotal role in several mitochondrial functions/parameters such as bioenergetics, dynamics, mitophagy, and apoptosis, which are involved in key steps of cancer aggressiveness (i.e., migration/invasion and resistance to treatment). Therefore, this review focuses on studies suggesting that changes in CL content and/or composition, as well as CL metabolism enzyme levels, may be linked with the progression and the aggressiveness of some types of cancer. Finally, we also introduce the main mitochondrial function in which CL could play a pivotal role with a special focus on its implication in cancer development and therapy. Show less

TLDR: Flow cytometry analysis showed that the gold conjugate induces significant arrest in S and G2/M phases primarily, whereas Erlotinib, as an inhibitor of epidermal growth factor receptor (EGFR), blocks G1/S transition and increases G1 cell population. Show less

Few data are available on the clinical impact of drug-drug interactions (DDIs). Most of the studies are limited to the analysis of exposure to potential DDI or the targeted impact of the combination of a few drugs or therapeutic classes. The analysis of adverse drug reaction (ADR) reports could be a mean to study generally the adverse effects identified due to a DDI. Our objective was to describe the characteristics of ADRs resulting from DDIs reported to the French Pharmacovigilance system and to identify the drugs most often implicated in these ADRs. Considering all ADR reports from January 01, 2012, to December 31, 2016, we identified all cases of ADR resulting from a DDI (DDI-ADRs). We then described these in terms of patients' characteristics, ADR seriousness, drugs involved (two or more per case), and ADR type. Of the 4,027 reports relating to DDI-ADRs, 3,303 were related to serious ADRs. Patients with serious DDI-ADRs had a median age of 76 years (interquartile range: 63-84); 53% were male. Of all serious DDI-ADRs, 11% were life-threatening and 8% fatal. In 36% of cases, the DDI causing the ADR involved at least three drugs. Overall, 8,424 different drugs were mentioned in the 3,303 serious DDI-ADRs considered. Altogether, drugs from the "antithrombotic agents" subgroup were incriminated in 34% of serious DDI-ADRs. Antidepressants were the second most represented therapeutic/pharmacological subgroup (5% of serious DDI-ADRs). Among the 3,843 ADR types reported in the 3,303 serious DDI-ADRs considered, the most frequently represented were hemorrhage (40% clinical hemorrhage; 6% biological hemorrhage), renal failure (8%), pharmacokinetic alteration (5%), and cardiac arrhythmias (4%). Hemorrhagic accidents are still an important part of serious ADRs resulting from DDIs reported in France. The other clinical consequences of DDIs seem less well identified by pharmacovigilance. Moreover, more than one-third of serious DDI-ADRs involved at least three drugs. Show less

The use of photodynamic therapy (PDT) against cancer has received increasing attention over recent years. However, the application of the currently approved photosensitizers (PSs) is limited by their poor aqueous solubility, aggregation, photobleaching and slow clearance from the body. To overcome these limitations, there is a need for the development of new classes of PSs with ruthenium(II) polypyridine complexes currently gaining momentum. However, these compounds generally lack significant absorption in the biological spectral window, limiting their application to treat deep-seated or large tumors. To overcome this drawback, ruthenium(II) polypyridine complexes designed in silico with (E,E')-4,4'-bisstyryl-2,2'-bipyridine ligands show impressive 1- and 2-Photon absorption up to a magnitude higher than the ones published so far. While nontoxic in the dark, these compounds are phototoxic in various 2D monolayer cells, 3D multicellular tumor spheroids and are able to eradicate a multiresistant tumor inside a mouse model upon clinically relevant 1-Photon and 2-Photon excitation. Show less

Ruthenium compounds are promising anticancer candidates owing to their lower side-effects and encouraging activities against resistant tumors. Half-sandwich piano-stool type Ru^II compounds of general formula [(L)Ru^II(η⁶-arene)(X)]⁺ (L = chelating bidentate ligand, X = halide) have exhibited significant therapeutic potential against cisplatin-resistant tumor cell lines. In Ru^II (p-cymene) based complexes, the change of the halide leaving group has led to several interesting features, viz., hydrolytic stability, resistance toward thiols, and alteration in pathways of action. Tyramine is a naturally occurring monoamine which acts as a catecholamine precursor in humans. We synthesized a family of N,N and N,O coordinated Ru^II (p-cymene) complexes, [(L)Ru^II(η⁶-arene)(X)]⁺ (1-4), with tyramine and varied the halide (X = Cl, I) to investigate the difference in reactivity. Our studies showed that complex 2 bearing N,N coordination with an iodido leaving group shows selective in vitro cytotoxicity against the pancreatic cancer cell line MIA PaCa-2 (IC₅₀ ca. 5 μM) but is less toxic to triple-negative breast cancer (MDA-MB-231), hepatocellular carcinoma (Hep G2), and the normal human foreskin fibroblasts (HFF-1). Complex 2 displays stability toward hydrolysis and does not bind with glutathione, as confirmed by ¹H NMR and ESI-HRMS experiments. The inert nature of 2 leads to enhancement of cytotoxicity (IC₅₀ = 5.3 ± 1 μM) upon increasing the cellular treatment time from 48 to 72 h. Show less

BACKGROUND: Psychological aspects of labor and birth have received little attention within maternity care service planning or clinical practice. The aim of this paper is to propose a model demonstrating how neurohormonal processes, in particular oxytocinergic mechanisms, not only control the physiological aspects of labor and birth, but also contribute to the subjective psychological experiences of birth. In addition, sensory information from the uterus as well as the external environment might influence these neurohormonal processes thereby influencing the progress of labor and the experience of birth. METHODOLOGY: In this new model of childbirth, we integrated the findings from two previous systematic reviews, one on maternal plasma levels of oxytocin during physiological childbirth and one meta-synthesis of women´s subjective experiences of physiological childbirth. FINDINGS: The neurobiological processes induced by the release of endogenous oxytocin during birth influence maternal behaviour and feelings in connection with birth in order to facilitate birth. The psychological experiences during birth may promote an optimal transition to motherhood. The spontaneous altered state of consciousness, that some women experience, may well be a hallmark of physiological childbirth in humans. The data also highlights the crucial role of one-to-one support during labor and birth. The physiological importance of social support to reduce labor stress and pain necessitates a reconsideration of many aspects of modern maternity care. CONCLUSION: By listening to women's experiences and by observing women during childbirth, factors that contribute to an optimized process of labor, such as the mothers' wellbeing and feelings of safety, may be identified. These observations support the integrative role of endogenous oxytocin in coordinating the neuroendocrine, psychological and physiological aspects of labor and birth, including oxytocin mediated. decrease of pain, fear and stress, support the need for midwifery one-to-one support in labour as well as the need for maternity care that optimizes the function of these neuroendocrine processes even when birth interventions are used. Women and their partners would benefit from understanding the crucial role that endogenous oxytocin plays in the psychological and neuroendocrinological process of labor. Show less

Two novel Ru(ii) polypyridyl complexes bearing imidazo-phenanthroline conjugated hydroxybenzoic acid groups were designed to enhance the tumor targeting ability as photosensitizers for photodynamic therapy. [Ru(bpy)2(phcpip)] (ClO4)2 (Ru-1) and [Ru(bpy)2(ohcpip)] (ClO4)2 (Ru-2) (bpy = 2,2'-bipyridine; phcpip = 2-(3-carboxyl-4-hydroxyphenyl) imidazo [4,5-f]phenanthroline; ohcpip = 2-(2-hydroxyl-3-carboxyphenyl) imidazo [4,5-f] [1,10] phenanthroline) were synthesized and their photodynamic antitumor activities were investigated. Both complexes displayed high photocytotoxicity toward cancerous cell lines HepG2, A549, MCF-7, and MDA-MB-231, but low photocytotoxicity toward normal cell lines GES-1 and Huvec. They were mainly localized at the nucleus of HepG2 cells after 24 h incubation, arrested the cell cycle at the G2/M phase and induced cancer cell apoptosis through reactive oxygen species (ROS) mediated pathways. Tumor targeting of the complexes is attributed to stronger molecular binding to DNA. Show less

Ferroptosis is a form of regulated cell death that is characterized by iron-dependent oxidative damage and subsequent plasma membrane ruptures and the release of damage-associated molecular patterns. Due to the role of iron in mediating the production of reactive oxygen species and enzyme activity in lipid peroxidation, ferroptosis is strictly controlled by regulators involved in many aspects of iron metabolism, such as iron uptake, storage, utilization, and efflux. Translational and transcriptional regulation of iron homeostasis provide an integrated network to determine the sensitivity of ferroptosis. Impaired ferroptosis is implicated in various iron-related pathological conditions or diseases, such as cancer, neurodegenerative diseases, and ischemia-reperfusion injury. Understanding the molecular mechanisms underlying the regulation of iron metabolism during ferroptosis may provide effective strategies for the treatment of ferroptosis-associated diseases. Indeed, iron chelators effectively prevent the occurrence of ferroptosis, which may provide new approaches for the treatment of iron-related disorders. In this review, we summarize recent advances in the theoretical modeling of iron-dependent ferroptosis, and highlight the therapeutic implications of iron chelators in diseases. Show less

This study was designed to develop a fast and convenient methodology for the preparation of 10-nonyl acridine orange (NAO) and its silyl analogues to improve their photo-physical properties for the detection and quantification of cardiolipin (CL). Optimized conditions allow the effective synthesis of NAO analogues with good yield and excellent purity. The introduction of a 3-(trimethylsilyl)propyl moiety improves the dye's solubility and stability in buffer solution and increases its emission intensity by ≈30%. The novel dye can be used for the selective quantification of CL in a liposomal inner mitochondrial membrane model with greater fluorescence intensity and linear slope compared to NAO. The novel silicon-containing NAO analogue has lower cytotoxicity, and is a convenient fluorescent dye for cell staining. Show less

The established platinum-based drugs form covalent DNA adducts to elicit their cytotoxic response. Although they are widely employed, these agents cause toxic side-effects and are susceptible to cancer-resistance mechanisms. To overcome these limitations, alternative metal complexes containing the rhenium(I) tricarbonyl core have been explored as anticancer agents. Based on a previous study ( Chem. Eur. J. 2019, 25, 9206), a series of highly active tricarbonyl rhenium isonitrile polypyridyl (TRIP) complexes of the general formula fac-[Re(CO)₃(NN)(ICN)]⁺, where NN is a chelating diimine and ICN is an isonitrile ligand, that induce endoplasmic reticulum (ER) stress via activation of the unfolded protein response (UPR) pathway are investigated. A total of 11 of these TRIP complexes were synthesized, modifying both the equatorial polypyridyl and axial isonitrile ligands. Complexes with more electron-donating equatorial ligands were found to have greater anticancer activity, whereas the axial ICN ligands had a smaller effect on their overall potency. All 11 TRIP derivatives trigger a similar phenotype that is characterized by their abilities to induce ER stress and activate the UPR. Lastly, we explored the in vivo efficacy of one of the most potent complexes, fac-[Re(CO)₃(dmphen)(ptolICN)]⁺ (TRIP-1a), where dmphen = 2,9-dimethyl-1,10-phenanthroline and ptolICN = para-tolyl isonitrile, in mice. The ^99mTc congener of TRIP-1a was synthesized, and its biodistribution in BALB/c mice was investigated in comparison to the parent Re complex. The results illustrate that both complexes have similar biodistribution patterns, suggesting that ^99mTc analogues of these TRIP complexes can be used as diagnostic partner agents. The in vivo antitumor activity of TRIP-1a was then investigated in NSG mice bearing A2780 ovarian cancer xenografts. When administered at a dose of 20 mg/kg twice weekly, this complex was able to inhibit tumor growth and prolong mouse survival by 150% compared to the vehicle control cohort. Show less

Highly cytotoxic AuI-dithiocarbamate complexes were designed to induce severe integrative stress in ovarian cancer cells, leading to the surface exposure of calreticulin, which is a first step in the activation of immune system. Show less

The transcription factor nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) is a central regulator of redox, metabolic, and protein homeostasis that intersects with many other signaling cascades. Although the understanding of the complex nature of NRF2 signaling continues to grow, there is only one therapeutic targeting NRF2 for clinical use, dimethyl fumarate, used for the treatment of multiple sclerosis. The discovery of new therapies is confounded by the fact that NRF2 levels vary significantly depending on physiological and pathological context. Thus, properly timed and targeted manipulation of the NRF2 pathway is critical in creating effective therapeutic regimens. In this review, we summarize the regulation and downstream targets of NRF2. Furthermore, we discuss the role of NRF2 in cancer, neurodegeneration, and diabetes as well as cardiovascular, kidney, and liver disease, with a special emphasis on NRF2-based therapeutics, including those that have made it into clinical trials. Show less

Novel phthiocol-based organometallics with in situ formed tridentate N,O,O-coordination motif were established via three-component microwave assisted one-pot reaction. These complexes exhibited enhanced stability in aqueous solution compared to the parental compound KP2048 and showed unexpected cytotoxic behaviour and selectivity in 2D and 3D cell cultures. Show less

Cancer is one of the highest prevalent diseases in humans. The chances of surviving cancer and its prognosis are very dependent on the affected tissue, body location, and stage at which the disease is diagnosed. Researchers and pharmaceutical companies worldwide are pursuing many attempts to look for compounds to treat this malignancy. Most of the current strategies to fight cancer implicate the use of compounds acting on DNA damage checkpoints, non-receptor tyrosine kinases activities, regulators of the hedgehog signaling pathways, and metabolic adaptations placed in cancer. In the last decade, the finding of a lipid peroxidation increase linked to 15-lipoxygenases isoform 1 (15-LOX-1) activity stimulation has been found in specific successful treatments against cancer. This discovery contrasts with the production of other lipid oxidation signatures generated by stimulation of other lipoxygenases such as 5-LOX and 12-LOX, and cyclooxygenase (COX-2) activities, which have been suggested as cancer biomarkers and which inhibitors present anti-tumoral and antiproliferative activities. These findings support the previously proposed role of lipid hydroperoxides and their metabolites as cancer cell mediators. Depletion or promotion of lipid peroxidation is generally related to a specific production source associated with a cancer stage or tissue in which cancer originates. This review highlights the potential therapeutical use of chemical derivatives to stimulate or block specific cellular routes to generate lipid hydroperoxides to treat this disease. Show less

The Ru(ii) complex of an imidazole-mesalazine Schiff base is a unique example showing growth inhibition of 3D-colon cancer stem cell spheroids and bulk colon cancer cells at lower dosage than salinomycin or oxaliplatin. Unlike oxaliplatin which increases the expression of stemness genes (SOX2, KLF4, HES1 and Oct4), these complexes maintain a tight regulation. Show less

The drug-resistance of cancer cells has become a major obstacle to the development of clinical drugs for chemotherapy. In order to overcome cisplatin-resistance, seven cyclometalated ruthenium(ii) complexes were synthesized with a varying degree of fluorine substitution, for use as anticancer agents. A cytotoxicity assay testified that the complexes possessed a more cytotoxic effect than cisplatin towards the cisplatin-resistant cell line A549R. The number of fluorine atoms regulated the lipophilicity of the complexes, but the relationship was not linear. Ru1 containing one fluorine atom had the highest lipophilicity and the best therapeutic effect. The complexes enter cells through an energy-dependent pathway and then localize in the nuclei and mitochondria. The complexes induced nuclear dysfunction by the inhibition of DNA replication as well as mitochondrial dysfunction by the loss of membrane potential. The damage to these vital organelles leads to cell apoptosis via the caspase 3/7 pathway. Our results indicated that the modulation of the number of fluorine atoms in therapeutic agents can have a profound effect and Ru1 is a complex with a high potential as a drug for the treatment of cisplatin-resistant cancer. Show less

Herein, we present a series of dual-targeted ruthenium-glucose conjugates that can function as two-photon absorption (TPA) PDT agents to effectively destroy tumors by preferentially targeting both tumor cells and mitochondria. The in vivo experiments revealed an excellent tumor inhibitory efficiency of the dual-targeted TPA PSs. Show less

Half-sandwich Cp*-Rh complexes containing curcuminoids ([Rh(η⁵-Cp*)(L)(Py)]PF₆, 1-3, L = curcuminoid ligands L¹-L³) were prepared, characterized and studied for anticancer activity. Complex 1 was structurally characterized by single-crystal X-ray crystallography. Complex 3 presented excellent photodynamic anticancer effect in light (>400 nm) showing IC₅₀ values of 7.5 and 4.3 μM against HepG2, SKOV3 and HeLa, respectively, along with the 12.4, 7.9 and 4.7-fold lower toxicity in the dark. Confocal fluorescence images show that the complex primarily targeted mitochondrial localization. These results suggest that the complex 3 was a valuable agent with higher efficacy for chemotherapy and photodynamic therapy, which can achieve real-time image guidance in cancer therapy for the fluorescence of the complex as imaging signals. This investigation provides a valuable route to design novel half-sandwich Cp*-Rh complexes with higher efficacy for photodynamic anticancer chemotherapy. Show less

Four triphenylamine/carbazole-modified half-sandwich ruthenium(ii) compounds [(η⁶-p-cymene)Ru(N/O^N)Cl]^0/+ with Schiff base chelating ligands (N/O^N) are synthesized and characterized. The introduction of Schiff base units effectively increases the antitumor activity of these compounds (IC₅₀: 1.70 ± 0.56-17.75 ± 3.10 μM), which, meanwhile, can inhibit the metastasis of tumor cells effectively. These compounds follow an energy-dependent cellular uptake mechanism, mainly accumulate in lysosomes to destroy their integrity, and then eventually promote apoptosis. In addition, these compounds can induce an increase of intracellular reactive oxygen species (ROS) levels and provide an antitumor mechanism of oxidation, which is confirmed by the decrease of mitochondrial membrane potential (MMP) and the catalytic oxidation of the coenzyme nicotinamide-adenine dinucleotide (NADH). All these indicate that these ruthenium(ii) compounds are expected to be dual-functional antitumor agents: anti-metastasis and lysosomal damage. Show less