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D’amato, A.; Mariconda, A.; Iacopetta, D.; Ceramella, J.; Catalano, A.; Sinicropi, M.S.; Longo, P. Ruthenium(II). Encyclopedia. Available online: https://encyclopedia.pub/entry/55930 (accessed on 29 April 2024).
D’amato A, Mariconda A, Iacopetta D, Ceramella J, Catalano A, Sinicropi MS, et al. Ruthenium(II). Encyclopedia. Available at: https://encyclopedia.pub/entry/55930. Accessed April 29, 2024.
D’amato, Assunta, Annaluisa Mariconda, Domenico Iacopetta, Jessica Ceramella, Alessia Catalano, Maria Stefania Sinicropi, Pasquale Longo. "Ruthenium(II)" Encyclopedia, https://encyclopedia.pub/entry/55930 (accessed April 29, 2024).
D’amato, A., Mariconda, A., Iacopetta, D., Ceramella, J., Catalano, A., Sinicropi, M.S., & Longo, P. (2024, March 06). Ruthenium(II). In Encyclopedia. https://encyclopedia.pub/entry/55930
D’amato, Assunta, et al. "Ruthenium(II)." Encyclopedia. Web. 06 March, 2024.
Ruthenium(II)
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This entry is adapted from the peer-reviewed paper 10.3390/ph16121729

The two Ru(III) and Ru(II) complexes, namely, BOLD-100 and RAPTA-C, are presently being studied in a clinical trial and preclinical studies evaluation, respectively, as anticancer agents. Ruthenium N-heterocyclic carbene (Ru-NHC) complexes show interesting properties in medicinal chemistry, exhibiting multiple biological activities, among them anticancer, antimicrobial, antioxidant, and anti-inflammatory. Among the newly synthesized complexes, RANHC-V and RANHC-VI are the most active against triple-negative human breast cancer cell lines MDA-MB-231. These compounds were selective in vitro inhibitors of the human topoisomerase I activity and triggered cell death by apoptosis. Furthermore, the Ru-NHC complexes’ antimicrobial activity was studied against Gram-positive and -negative bacteria, revealing that all the complexes possessed the best antibacterial activity against the Gram-positive Staphylococcus aureus, at a concentration of 0,025 mg/mL. Finally, the antioxidant effect was assessed by DPPH and ABTS radicals scavenging assays, resulting in a higher ability for inhibiting the ABTS+, with respect to the well-known antioxidant Trolox. Thus, this work provides encouraging insights for further development of novel Ru-NHC complexes as potent chemotherapeutic agents endowed with multiple biological properties.

ruthenium(II) complexes dual antitumor/antiviral agents p-cymene

1. Introduction

For many years, numerous researchers have actively worked in the field of inorganic drugs developing several metal complexes with diverse biological activities [1], such as anticancer [2][3][4][5][6][7][8] antibacterial [9], antioxidant [10], and antiviral [11][12][13]. During the COVID-19 pandemic [14], numerous studies have addressed using metal complexes in the hope of finding new strategies to cure the disease [15][16][17]. A comprehensive survey of the anti-COVID-19 options available using metal complexes has been recently reported by Gopal et al. (2023) [18]. Among the precious metals, ruthenium (Ru) has singular physicochemical properties, which makes it particularly useful in drug design [19]. Ru complexes represent an important class of metallo-organic compounds with numerous applications, and they are currently used in the fields of catalysis [20][21][22][23], including homogeneous, heterogeneous, and photocatalysis [24]. Moreover, numerous biological activities, such as antifungal [25], antibacterial [26], and anticarcinogenic [27][28][29][30][31][32], have been described for the complexes of Ru, as well as their uses in neurodegenerative diseases [33]. Several complexes with Ru(II) have been reported, including those with benzoic acid and their analogues [34], naphthoquinones, flavonoids, curcumins [35], N-heterocyclic carbenes (NHCs) [36], polypyridyl [37], phenanthroline [38], thiazole [39], Schiff bases [40][41][42][43], and half-sandwiched arene complexes [44]. Specifically, Ru complexes are widely studied in colorectal cancer [45], breast cancer [46], lung cancer [47], and prostate cancer [48]. Thota et al. (2018) recently described the importance of Ru(II) complexes as anticancer agents [49]. Ru(II) complexes show several advantages over traditional platinum-based chemotherapeutics, such as stability in biological media due to their higher redox potentials, which allows for longer circulation times in the body, thereby increasing the amount of time that the complexes have to target tumor cells [50]; selectivity towards tumor cells and minimal side effects, which are probably due to differences in the redox potentials or metal ion binding properties of tumor cells versus healthy cells [51]; easier accessibility for synthetic routes; low costs associated with the overall process; and, finally, Ru(II) complexes can be administered through a variety of routes, including oral, intravenous, and intraperitoneal. It is strongly believed that Ru(III) species act as prodrugs, and they are converted into Ru(II) species due to the hypoxic environment within the cancer cells [52][53][54]. Ru complexes are also studied in photodynamic therapy, photochemotherapy, and photothermal therapy [55]. With these activities, Ru can help to trigger antitumor activity only in desirable areas of the body or in cancer cells, apart from classical chemotherapeutic action [56][57]. Over the last two decades, the complexes of ruthenium have been also studied for their antioxidant [58], antimicrobial [59], and antiviral activities [60][61]. Moreover, the modulation activity of amyloid-β aggregation has been described, which can be useful in the treatment of Alzheimer’s disease [62][63]. Ru(II) and Ru(III) complexes are currently objects of great attention in the field of medicinal chemistry as antitumor agents with selective antimetastatic properties and low systemic toxicity [64][65][66][67]. The pharmacological activity of metal complexes can be attributed to either the metal itself, its ligands, or both, depending on the structure of the complex. The ruthenate anion itself may interact with cellular targets or simply act as a scaffold to carry bioactive ligands to a target site [26][68]. Ru-based compounds, as well as other metal complexes, act via a myriad of mechanisms, which usually involve interactions with DNA or various proteins such as enzymes and transcription factors [68]. Ru complexes, as well as platinum complexes, are generally defined as “multitargeted”, since they not only target DNA, but also contain either a vector to enable them to target cancer cells selectively and/or moieties that target enzymes, peptides, and intracellular proteins [69]. Several studies are addressed here to understand the mechanism of action of Ru(II) complexes. Recently, a probable mechanism of transfer hydrogenation catalysis with respect to anticancer activity has been described for Ru–arene complexes [70]. Moreover, a recent review on Ru(II) complexes suggested that metal-based candidate drugs are promising modulators of cytoskeletal and cytoskeleton-associated proteins [71]. Recently, Ru and rhodium complexes have been suggested as promising agents for metalloimmunotherapy [72].
In the fight against cancer, three Ru(III) coordination complexes (NAMI-A, KP1019, and BOLD-100) and one Ru(II) coordination complex (TLD1433) have advanced to clinical trials (Figure 1) [73]. Inside the tumor, Ru(III) is proposed to be activated by its reduction to Ru(II) due to prevalent reductive conditions. The Ru(III) complexes are tetrachloride complexes with axial N-heterocyclic ligands. NAMI-A exhibited strong inhibitory effectiveness against tumor malignancy and metastasis, thereby preventing the development of the growth of tumors. It entered phase II trials, but due to limited efficacy and acute side effects in many patients, it could not proceed further for clinical development [74]. The Ru(III) complex sodium BOLD-100 is among the most widely investigated nonplatinum metal-based anticancer drugs [75]. It was studied as a substitution of the Ru complex KP1019, which entered phase I trials for colorectal tumors, but its further development was halted due to its low solubility [76]. KP1019 is known to be active against primary tumors, while NAMI-A is active against secondary tumors via antiangiogenic and antimetastatic activities [6]. NAMI-A and KP1019 have been shown to bind to DNA, RNA, and proteins [77]. The octahedral polypyridyl Ru(II) complex TLD1433 has potential as a photosensitizer for photodynamic therapy in the treatment of bladder cancer [78].
Figure 1. Structures of Ru(III) and Ru(II) complexes in clinical and preclinical trials.
Ru(II) complexes, namely RM175, RAED-C, and RAPTA-C, are 18-electron Ru–arene “piano-stool” complexes, in which an η6-arene ring stabilizes the 2+ oxidation state of the Ru metal center [73]. These complexes entered into preclinical studies because of their appealing anticancer properties [79]. RM175 was the first Ru(II) complex reported to have potential for anticancer activity. RM175 has undergone successful in vitro and in vivo cytotoxic assessment and has shown efficient cytotoxicity in vitro, with IC50 values similar to that of cisplatin [80]. RM175 shows a mechanism of action similar to cisplatin through its interaction with guanine. The possible mechanism of interaction has been recently elucidated by Prathima et al. (2023) [6]. However, it differs from cisplatin, as it revealed no cross-resistance against cisplatin-resistant ovarian carcinoma cells (A2780cis); this is indicative of a distinctive mode of anticancer action and has also been reported to trigger p53-dependent cell-cycle arrest [81]. Ru(II)–arene RAED-type compounds (ED = ethylenediamine) and Ru(II)–arene RAPTA-type compounds (PTA = 1,3,5-triaza-7-phosphaadamantane or 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decanephosphine) were developed by the groups of Sadler [82] and Dyson [83], respectively. Both have the p-cymene moiety, that is, 1-methyl-4-(propan-2-yl)benzene. The RAED series was first reported in 2001 by Morris et al. [84], and these compounds are able to coordinate with DNA through the N7 of guanine residues and, when bearing an extended arene ligand such as biphenyl, dihydroanthracene, or tetrahydroanthracene, may concomitantly intercalate in DNA. These compounds are cytotoxic against diverse cancer cell lines, including cisplatin-resistant strains [85]. Swaminatan et al. (2022) [86] reported that RAED-C is highly active in primary tumors, whereas RAPTA-C is inactive in primary tumors but possesses antimetastatic and antiangiogenic properties. Moreover, the former preferentially forms adducts at the DNA sites with only one additional binding site at the histone level, while the latter preferably forms adducts at the histone protein sites residing on the surface of the nucleosome core. Hildebrandt et al. (2022) [87] have recently reported that both compounds, RAPTA-C and RM175, are being studied in advanced clinical studies. However, to our knowledge, no other research confirms this statement.
Moreover, the drug delivery forms of Ru complexes have also been studied as antitumor drugs for combination therapy [88]. Finally, and very importantly, dual-active drugs are a concept that has been noted as an imperative in future drug design. The development of novel drugs that can have double biological behavior (anticancer–antiviral, anticancer–antimicrobial, etc.), leading to the opportunity to treat two different diseases, has been recently widely addressed [89][90][91][92].

2. Ruthenium(II/III) Complexes in Clinic Trials and Advanced Preclinical Studies as Anticancer Agents

2.1. BOLD-100

The Ru(III) complex sodium trans-tetrachlorobis(1H-indazole)ruthenate(III) (BOLD-100, formerly known as NKP-1339, KP1339, and IT-139) is a double prodrug that undergoes hydrolysis via the ligand exchange of chloride ligands and subsequent reduction to Ru(II) [93][94]. BOLD-100 is a versatile small molecule with manifold intracellular modes of action, which were previously summarized by the research group that synthesized this molecule [95]. In clinical phase I evaluation, BOLD-100 therapy led to disease stabilization and even partial response in various types of advanced solid tumors, including colorectal cancer, non-small-cell lung cancer, and neuroendocrine tumors of carcinoid origin [96]. BOLD-100 was granted an orphan drug designation (ODD) in gastric and pancreatic cancers [97]. It is currently in a phase 2a clinical trial in combination with folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX regimen) for the treatment of advanced solid tumors, such as colorectal, pancreatic, and gastric cancers, as well as cholangiocarcinoma (NCT04421820) [98][99]. Moreover, BOLD-100 has also demonstrated increased activity in the cell lines from esophageal cancer, blood cancers, and bladder cancer [100]. BOLD-100 has also recently gained particular interest for its potential multiple activities. Earlier, the drug had won orphan drug titles for its indication of pancreatic cancer [98][100]. Besides its undiscussed anticancer activity, it has been recently demonstrated that this compound is also a potent inhibitor of the replication of human immunodeficiency virus type 1 (HIV-1), human adenovirus type 5, and SARS-CoV-2 in vitro [101]. Repression of the genes involved in DNA repair, the induction of reactive oxygen species (ROS), and interference with ribosomal proteins seem to be results of BOLD-100 activity [75]. Moreover, BOLD-100 is an inhibitor of glucose-regulated protein 78 kDa (GRP78) (WO/2017/151762), thus disrupting endoplasmic reticulum homeostasis, inducing endoplasmic reticulum stress, and eliciting an unfolded protein response [102]. This is reflected by the phosphorylation of the eukaryotic translation initiation factor 2A [103] and caspase-8-dependent cell death [104]. The suppression of Grp78 transcription is a mechanism described for antiviral activity, which has also been demonstrated against SARS-CoV-2 [105]. Moreover, in vitro studies have demonstrated that this compound triggers an immunogenic cell death (ICD) signature hallmarked by the phosphorylation of PERK, the eukaryotic translation initiation factor 2α (eIF2α) exposure of calreticulin on the cell membrane, the release of the high mobility group box 1, and the secretion of ATP [106]. Interestingly, Mucke (2022) [107] reported that BOLD-100 inhibited the cytopathic activity in an assay based on Vero-E6 cell lines infected with the Wuhan strain of the virus: the absolute EC50 value for preinfection protection by BOLD-100 was 1.9 μM, whereas postinfection treatment required 1.8 μM. This value is orders of magnitude lower than the 200–400 mM cytotoxicity limit for BOLD-100 in this cell line, and it is much lower than the respective values for the antiviral remdesivir [108]. At 200 μM, the cytopathy of 293T-ACE2 human kidney cells (which express the ACE2 receptor) infected with the ‘California variant’ of the B.1.1.7 viral strain was prevented by BOLD-100 [107]. Yet, a general limitation of systemic cancer therapy efficacy is the acquisition of treatment resistance [109]. The mechanism against solid tumors that has been recently suggested is related to its ability to inhibit glycolysis and render cells vulnerable to glucose-deficient metabolism [110]. It is known that, besides other metabolic changes, including alterations in oxidative phosphorylation or glutaminolysis [111], several types of solid cancers show improved glycolysis to convert glucose to lactate, even under aerobic conditions: this effect is called the “Warburg effect” [112]. BOLD-100 demonstrated a significant glycolysis-blocking anti-Warburg effect as a novel mechanism of action. Thus, glycolysis inhibition has also been suggested as a potential strategy to overcome acquired BOLD-100 resistance and enhance BOLD-100 anticancer activity. Moreover, an upregulated glucose uptake was detected in combination with BOLD-100 exposure [110]. Baier et al. (2023) [113] recently identified BOLD-100 as an epigenetically active substance targeting several oncometabolic pathways. The authors suggested that acquired BOLD-100-resistant colon and pancreatic carcinoma cells may be related to lipid metabolism. BOLD-100 significantly reduced the production and release of lactate, which is a major immunosuppressive metabolite. The existence of crosstalk between BOLD-100 exposure, acquired resistance, and histone acetylation has been suggested.

2.2. TLD1433

TLD1433 (also known as Ruvidar® and “Theralase®) was the first Ru(II)-based photosensitizer to enter clinical trials and successfully complete a phase 1b human clinical trial (NCT03053635). A phase 2 study is ongoing (NCT03945162) [114][115] to evaluate TLD1433 in non-muscle-invasive bladder cancer patients. It has been recently suggested as a repositioning drug for the treatment of conjunctival melanoma, which is a rare but often deadly ocular cancer [116], and human lung adenocarcinoma [117]. Recently, Karges (2022) [118] reviewed the clinical development of TLD1433 and other metal-containing compounds, including rostaporfin (Purlytin®), motexafin lutetium (Lutrin®/Antrin®), and the sulfonated aluminium phthalocyanin (Photosens®), bearing the different metals Sn, Lu, and Al, respectively, as well as padeliporfin (WST09) and padeliporfin (WST11 or TOOKAD® soluble), which contain Pd, as photosensitizers for the photodynamic therapy of cancer.

2.3. RAPTA-C

The therapeutic potential of Ru(II)–arene RAPTA-type compounds (PTA = 1,3,5-triaza-7-phosphaadamantane or 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decanephosphine) has been thoroughly investigated, thus owing to the excellent antimetastatic property of the initial candidate RAPTA-C [Ru(η6-p-cymene)Cl2(PTA)] [119]. It is a multitargeting drug candidate that has demonstrated pH-dependent DNA damage, inhibited the enzyme activity of cathepsin-B and thioredoxin reductase, and showed selectivity towards the hypoxic environment of cancer cells [120]. It represents an innovative antitumor therapy and a better-tolerated alternative to Pt-based chemotherapeutic drugs in the treatment of tumors, as it exhibits antitumoral, antimetastatic, and antiangiogenic activities through protein and histone–deoxyribonucleic acid alterations [121]. RAPTA-C acts synergistically in association with other drugs, such as the EGFR inhibitor erlotinib, the tyrosine kinase inhibitor axitinib, PI3K, and the mTOR inhibitor BEZ-235, as demonstrated by in vivo models [122][123][124][125]. The study by Weiss et al. (2014) [126] demonstrated that RAPTA-C caused a reduction in the growth of primary tumors in preclinical models for ovarian (A2780 ovarian carcinoma transplanted onto a chicken chorioallantoic membrane model) and colorectal (in LS174T colorectal carcinoma in athymic mice) carcinomas. Moreover, the clearance rate of RAPTA-C from the organs and the bloodstream was studied using RAPTA-C that incorporated radio-labeled (103Ru). Biodistribution studies with radio-labeled (103Ru) RAPTA-C demonstrated that the compound is rapidly cleared from the organs and the bloodstream through excretion by the kidneys. Recently, the combination of RAPTA-C and paclitaxel based on fructose-coated nanoparticles has been suggested as a dual drug delivery system for the treatment of metastatic cancer. The dual drug delivery system was studied via in vitro tests using MDA-MB-231 breast cancer cells, and it was observed that RAPTA-C, in combination with paclitaxel, significantly enhanced antitumor and antimetastatic action [127].

3. Ruthenium Complexes Acting against Viruses

Several metal-based drugs have been described regarding their antiviral activities, thereby highlighting the potential for these metal-based drugs to be used in treating COVID-19 [17][128][129][130][131]. Although many studies have described the anticancer activity of Ru complexes, there are very few reports on their antiviral activity [129][132][133]. Recently, Gil-Moles and colleagues (2021) [134] described some metallodrugs, including Ru complexes, and their activity against SARS-CoV-2. Some complexes were potent inhibitors of essential SARS-CoV-2 targets, such as the SARS-CoV-2 spike protein/host ACE2 receptor interaction and the SARS-CoV-2 papain-like protease (PLpro). Moreover, Janković et al. (2022) [135] reported other Ru complexes as potent antivirals against SARS-CoV-2, which target the papain-like proteases PLpro and Mpro. They are shown in the next paragraphs. De Oliveira et al. (2020) [61] described their antiviral activity against other viruses, such as the Chikungunya virus, thereby highlighting the potential of Ru-based compounds as broad-acting antivirals.

References

  1. Singh, V.K.; Singh, V.K.; Mishra, A.; Singh, A.A.; Prasad, G.; Singh, A.K. Recent advancements in coordination compounds and their potential clinical application in the management of diseases: An up-to-date review. Polyhedron 2023, 241, 116485.
  2. De, S.; Kazi, S.; Banerjee, S.; Banerjee, S.; Sarkar, N.; Shah, S.K.; Kuo, Y.-C.; Kumar, S.A. Metallotherapeutic complexes with high selective properties for anti-neoplastic therapy. Coord. Chem. Rev. 2024, 498, 215462.
  3. Gamberi, T.; Hanif, M. Metal-based complexes in cancer treatment. Biomedicines 2022, 10, 2573.
  4. Paprocka, R.; Wiese-Szadkowska, M.; Janciauskiene, S.; Kosmalski, T.; Kulik, M.; Helmin-Basa, A. Latest developments in metal complexes as anticancer agents. Coord. Chem. Rev. 2022, 452, 214307.
  5. Ceramella, J.; Mariconda, A.; Sirignano, M.; Iacopetta, D.; Rosano, C.; Catalano, A.; Saturnino, C.; Sinicropi, M.S.; Longo, P. Novel Au carbene complexes as promising multi-target agents in breast cancer treatment. Pharmaceuticals 2022, 15, 507.
  6. Prathima, T.S.; Choudhury, B.; Ahmad, M.G.; Chanda, K.; Balamurali, M.M. Recent developments on other platinum metal complexes as target-specific anticancer therapeutics. Coord. Chem. Rev. 2023, 490, 215231.
  7. Bruijnincx, P.C.; Sadler, P.J. New trends for metal complexes with anticancer activity. Curr. Opin. Chem. Biol. 2008, 12, 197–206.
  8. Todorov, L.; Kostova, I. Recent Trends in the development of novel metal-based antineoplastic drugs. Molecules 2023, 28, 1959.
  9. Esquezaro, P.G.; Manzano, C.M.; Nakahata, D.H.; ISantos, I.A.; Ruiz, U.E.; Santiago, M.B.; Silva, N.B.; Martins, C.H.; Pereira, D.H.; Bergamini, F.R.G.; et al. Synthesis, spectroscopic characterization and in vitro antibacterial and antiviral activities of novel silver(I) complexes with mafenide and ethyl-mafenide. J. Mol. Struct. 2021, 1246, 131261.
  10. El-Lateef, H.M.A.; El-Dabea, T.; Khalaf, M.M.; Abu-Dief, A.M. Recent overview of potent antioxidant activity of coordination compounds. Antioxidants 2023, 12, 213.
  11. Abate, C.; Carnamucio, F.; Giuffrè, O.; Foti, C. Metal-Based Compounds in Antiviral Therapy. Biomolecules 2022, 12, 933.
  12. Singh, A.K.; Kumar, A.; Singh, H.; Sonawane, P.; Pathak, P.; Grishina, M.; Yadav, J.P.; Verma, A.; Kumar, P. Metal Complexes in cancer treatment: Journey so far. Chem. Biodivers. 2023, 20, e202300061.
  13. Anthony, E.A.; Bolitho, E.M.; Bridgewater, R.J.; Carter, O.W.L.; Donnelly, J.M.; Imberti, C.; Lant, E.C.; Lermyte, F.; Needham, R.J.; Palau, M.; et al. Metallodrugs are unique: Opportunities and challenges of discovery and development. Chem. Sci. 2020, 11, 12888–12917.
  14. Iacopetta, D.; Ceramella, J.; Catalano, A.; Saturnino, C.; Pellegrino, M.; Mariconda, A.; Longo, P.; Sinicropi, M.S.; Aquaro, S. COVID-19 at a glance: An up-to-date overview on variants, drug design and therapies. Viruses 2022, 14, 573.
  15. Pal, M.; Musib, D.; Roy, M. Transition metal complexes as potential tools against SARS-CoV-2: An in silico approach. New J. Chem. 2021, 45, 1924.
  16. Cirri, D.; Pratesi, A.; Marzo, T.; Messori, L. Metallo therapeutics for COVID-19. Exploiting metal-based compounds for the discovery of new antiviral drugs. Expert Opin. Drug Discov. 2021, 16, 39–46.
  17. Karges, J.; Cohen, S.M. Metal complexes as antiviral agents for SARS-CoV-2. ChemBioChem 2021, 22, 2600–2607.
  18. Gopal, J.; Muthu, M.; Sivanesan, I. A Comprehensive survey on the expediated anti-COVID-19 options enabled by metal complexes—Tasks and trials. Molecules 2023, 28, 3354.
  19. Allardyce, C.S.; Dyson, P.J. Ruthenium in medicine: Current clinical uses and future prospects. Platin. Met. Rev. 2001, 45, 62–69.
  20. D’Amato, A.; Mariconda, A.; Longo, P. New insights into the catalytic activity of second generation Hoveyda–Grubbs complexes having phenyl substituents on the backbone. Inorganics 2023, 11, 244.
  21. Rajabi, S.; Rüttger, F.; Lücken, J.; Dechert, S.; John, M.; Meyer, F. Ruthenium Complexes of Rigid, Dianionic, Tetradentate N-Donor Ligands and their Potential as Catalysts for Water Oxidation. Eur. J. Inorg. Chem. 2023, 26, e202200597.
  22. Yang, F.; Zhou, P.; Huang, Z.; Liao, J.; Huang, G.; Liang, T.; Zhang, Z. Ruthenium(II)-catalyzed remote C–H sulfonylation of 2-pyridones. Org. Lett. 2023, 25, 5779–5783.
  23. Gobbo, A.; Ma, X.; Ciancaleoni, G.; Zacchini, S.; Biancalana, L.; Guelfi, M.; Pampaloni, G.; Nolan, S.P.; Marchetti, F. Ruthenium(II) tris-pyrazolylmethane complexes in transfer hydrogenation reactions. Eur. J. Inorg. Chem. 2023, 26, e202300078.
  24. Hafeez, J.; Bilal, M.; Rasool, N.; Hafeez, U.; Adnan Ali Shah, S.; Imran, S.; Amiruddin Zakaria, Z. Synthesis of ruthenium complexes and their catalytic applications: A review. Arab. J. Chem. 2022, 15, 104165.
  25. Donnici, C.L.; Araujo, M.H.; Stoianoff, M.A.R. Ruthenium complexes as antifungal agents. In Ruthenium Complexes; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2018; pp. 293–318.
  26. Munteanu, A.C.; Uivarosi, V. Ruthenium complexes in the fight against pathogenic microorganisms. An extensive review. Pharmaceutics 2021, 13, 874.
  27. Kostova, I. Ruthenium complexes as anticancer agents. Curr. Med. Chem. 2006, 13, 1085–1107.
  28. Shutkov, I.A.; Okulova, Y.N.; Mazur, D.M.; Melnichuk, N.A.; Babkov, D.A.; Sokolova, E.V.; Spasov, A.A.; Milaeva, E.R.; Nazarov, A.A. New organometallic Ru(II) compounds with lonidamine motif as antitumor agents. Pharmaceutics 2023, 15, 1366.
  29. Pete, S.; Roy, N.; Kar, B.; Paira, P. Construction of homo and heteronuclear Ru(II), Ir(III) and Re(I) complexes for target specific cancer therapy. Coord. Chem. Rev. 2022, 460, 214462.
  30. Ribeiro, G.H.; Costa, A.R.; de Souza, A.R.; da Silva, F.V.; Martins, F.T.; Plutin, A.M.; Batista, A.A. An overview on the anticancer activity of Ru(II)/acylthiourea complexes. Coord. Chem. Rev. 2023, 488, 215161.
  31. Rafols, L.; Josa, D.; Aguila, D.; Barrios, L.A.; Roubeau, O.; Cirera, J.; Soto-Cerrato, V.; Pérez-Tomás, R.; Martinez, M.; Grabulosa, A. Piano-stool ruthenium(II) complexes with delayed cytotoxic activity: Origin of the lag time. Inorg. Chem. 2021, 60, 7974–7990.
  32. Wang, Z.F.; Huang, X.Q.; Wu, R.C.; Xiao, Y.; Zhang, S.H. Antitumor studies evaluation of triphenylphosphine ruthenium complexes with 5, 7-dihalo-substituted-8-quinolinoline targeting mitophagy pathways. J. Inorg. Biochem. 2023, 248, 112361.
  33. Florio, D.; La Manna, S.; Annunziata, A.; Iacobucci, I.; Monaco, V.; Di Natale, C.; Mollo, V.; Ruffo, F.; Monti, M.; Marasco, D. Ruthenium complexes bearing glucosyl ligands are able to inhibit the amyloid aggregation of short histidine-peptides. Dalton Trans. 2023, 52, 8549.
  34. Honorato, J.; Oliveira, K.M.; Leite, C.M.; Colina-Vegas, L.; Nóbrega, J.A.; Castellano, E.E.; Ellena, J.; Correa, R.S.; Batista, A.A. “Half-sandwich”/Ru II anticancer complexes containing triphenylphosphine and p-substituted benzoic acids. J. Brazil. Chem. Soc. 2020, 31, 2237–2249.
  35. Srivastava, P.; Shukla, M.; Kaul, G.; Chopra, S.; Patra, A.K. Rationally designed curcumin based Ruthenium(II) antimicrobials effective against drug-resistant: Staphylococcus aureus. Dalton Trans. 2019, 48, 11822–11828.
  36. Catalano, A.; Mariconda, A.; Sinicropi, M.S.; Ceramella, J.; Iacopetta, D.; Saturnino, C.; Longo, P. Biological activities of ruthenium NHC complexes: An update. Antibiotics 2023, 12, 365.
  37. Hu, H.; Zhang, H.; Zhong, R.; Yang, Y.; Huang, C.; Chen, J.; Liang, L.; Chen, Y.; Liu, Y. Synthesis, RNA-sequence and evaluation of anticancer efficacy of ruthenium(II) polypyridyl complexes toward HepG2 cells. J. Inorg. Biochem. 2023, 244, 112230.
  38. Huang, C.; Zhang, H.; Yang, Y.; Liu, H.; Chen, J.; Wang, Y.; Liang, L.; Hu, H.; Liu, Y. Synthesis, characterization, molecular docking, RNA-sequence and anticancer efficacy evaluation in vitro of ruthenium(II) complexes on B16 cells. J. Inorg. Biochem. 2023, 247, 112329.
  39. Khan, R.A.; Alterary, S.S.; BinSharfan, I.I.; Alsaeedi, H.; AlFawaz, A.; Khan, M.S.; Jaafar, M.H.; Shi, Y.; Arman, H.D.; Alsalme, A. Piano-stool type (η6-p-cymene) ruthenium(II) thiazole-derived motifs complexes: Synthesis, crystal structures, DFT studies, molecular docking and in-vitro binding studies with HSA and cytotoxicity. Inorg. Chim. Acta 2022, 537, 120925.
  40. Iacopetta, D.; Ceramella, J.; Catalano, A.; Mariconda, A.; Giuzio, F.; Saturnino, C.; Longo, P.; Sinicropi, M.S. Metal Complexes with Schiff Bases as Antimicrobials and Catalysts. Inorganics 2023, 11, 320.
  41. Sinicropi, M.S.; Ceramella, J.; Iacopetta, D.; Catalano, A.; Mariconda, A.; Rosano, C.; Saturnino, C.; El-Kashef, H.; Longo, P. Metal complexes with Schiff bases: Data collection and recent studies on biological activities. Int. J. Mol. Sci. 2022, 23, 14840.
  42. Parveen, S. Recent advances in anticancer ruthenium Schiff base complexes. Appl. Organometal. Chem. 2020, 34, e5687.
  43. Međedović, M.; Mijatović, A.; Baošić, R.; Lazić, D.; Milanović, Ž.; Marković, Z.; Milovanović, J.; Arsenijević, D.; Stojanović, B.; Arsenijević, M. Synthesis, characterization, biomolecular interactions, molecular docking, and in vitro and in vivo anticancer activities of novel ruthenium(III) Schiff base complexes. J. Inorg. Biochem. 2023, 248, 112363.
  44. Sumithaa, C.; Ganeshpandian, M. Half-sandwich ruthenium arene complexes bearing clinically approved drugs as ligands: The importance of metal–drug synergism in metallodrug design. Mol. Pharm. 2023, 20, 1453–1479.
  45. Mahmud, K.M.; Niloy, M.S.; Shakil, M.S.; Islam, M.A. Ruthenium complexes: An alternative to platinum drugs in colorectal cancer treatment. Pharmaceutics 2021, 13, 1295.
  46. Popolin, C.P.; Cominetti, M.R. A review of ruthenium complexes activities on breast cancer cells. Mini-Rev. Med. Chem. 2017, 17, 1435–1441.
  47. Sun, Q.; Li, Y.; Shi, H.; Wang, Y.; Zhang, Q. Ruthenium complexes as promising candidates against lung cancer. Molecules 2021, 26, 4389.
  48. Paulus, L.; Gallardo-Villagrán, M.; Carrion, C.; Ouk, C.; Martin, F.; Therrien, B.; Léger, D.Y.; Liagre, B. The effect of photosensitizer metalation incorporated into arene–ruthenium assemblies on prostate cancer. Int. J. Mol. Sci. 2023, 24, 13614.
  49. Thota, S.; Rodrigues, D.A.; Crans, D.C.; Barreiro, E.J. Ru(II) compounds: Next-generation anticancer metallotherapeutics? J. Med. Chem. 2018, 61, 5805–5821.
  50. Dyson, P.J.; Sava, G. Metal-Based Antitumour Drugs in the Post Genomic Era. Dalton Trans. 2006, 16, 1929–1933.
  51. Hong, W.X.; Huang, F.; Huan, T.; Xu, X.; Han, Q.; Wang, G.; Xu, H.; Duan, S.; Duan, Y.; Long, X.; et al. Comparative studies on DNA-binding and in vitro antitumor activity of enantiomeric ruthenium(II) complexes. J. Inorg. Biochem. 2018, 180, 54–60.
  52. Sonkar, C.; Sarkar, S.; Mukhopadhyay, S. Ruthenium (II)–arene complexes as anti-metastatic agents, and related techniques. RSC Med. Chem. 2022, 13, 22–38.
  53. Abid, M.; Shamsi, F.; Azam, A. Ruthenium complexes: An emerging ground to the development of metallopharmaceuticals for cancer therapy. Mini Rev. Med. Chem. 2016, 16, 772–786.
  54. Kanaoujiya, R.; Singh, M.; Singh, J.; Srivastava, S. Ruthenium based anticancer compounds and their importance. J. Sci. Res. 2020, 64, 264–268.
  55. Silva, M.J.S.A.; Vinck, R.; Wang, Y.; Saubaméa, B.; Tharaud, M.; Dominguez-Jurado, E.; Karges, J.; Gois, P.M.P.; Gasser, G. Towards selective delivery of a ruthenium(II) polypyridyl complex-containing bombesin conjugate into cancer cells. ChemBioChem 2023, 24, e202200647.
  56. Kundu, B.K.; Mukhopadhyay, S. Target based chemotherapeutic advancement of ruthenium complexes. Coord. Chem. Rev. 2021, 448, 214169.
  57. Yang, G.G.; Su, X.X.; Liang, B.B.; Pan, Z.Y.; Cao, Q.; Mao, Z.W. A platinum–ruthenium hybrid prodrug with multi-enzymatic activities for chemo-catalytic therapy of hypoxic tumors. Chem. Sci. 2022, 13, 11360–11367.
  58. Juszczak, M.; Kluska, M.; Kosińska, A.; Rudolf, B.; Woźniak, K. Antioxidant activity of ruthenium cyclopentadienyl complexes bearing succinimidato and phthalimidato ligands. Molecules 2022, 27, 2803.
  59. Małecka, M.; Skoczyńska, A.; Goodman, D.M.; Hartinger, C.G.; Budzisz, E. Biological properties of ruthenium (II)/(III) complexes with flavonoids as ligands. Coord. Chem. Rev. 2021, 436, 213849.
  60. Allardyce, C.S.; Dyson, P.J.; Ellis, D.J.; Salter, P.A.; Scopelliti, R. Synthesis and characterisation of some water soluble ruthenium(II)–arene complexes and an investigation of their antibiotic and antiviral properties. J. Organomet. Chem. 2003, 668, 35–42.
  61. de Oliveira, D.M.; Santos, I.D.A.; Martins, D.O.S.; Gonçalves, Y.G.; Cardoso-Sousa, L.; Sabino-Silva, R.; Von Poelhsitz, G.; Franca, E.D.F.; Nicolau-Junior, N.; Pacca, C.C.; et al. Organometallic complex strongly impairs Chikungunya virus entry to the host cells. Front. Microbiol. 2020, 11, 608924.
  62. Wu, C.Y.; Chen, H.J.; Wu, Y.C.; Tsai, S.W.; Liu, Y.H.; Bhattacharya, U.; Lin, D.; Tai, H.C.; Kong, K.V. Highly efficient singlet oxygen generation by BODIPY–ruthenium(II) complexes for promoting neurite outgrowth and suppressing Tau Protein aggregation. Inorg. Chem. 2023, 62, 1102–1112.
  63. Yawson, G.K.; Will, M.F.; Huffman, S.E.; Strandquist, E.T.; Bothwell, P.J.; Oliver, E.B.; Apuzzo, C.F.; Platt, D.C.; Weitzel, C.S.; Jones, M.A.; et al. A dual-pronged approach: A ruthenium(III) complex that modulates amyloid-β aggregation and disrupts its formed aggregates. Inorg. Chem. 2022, 61, 2733–2744.
  64. Guo, L.; Li, P.; Li, J.; Gong, Y.; Li, X.; Liu, Y.; Yu, K.; Liu, Z. Half-sandwich iridium(III), rhodium(III), and ruthenium(II) complexes chelating hybrid sp2-N/sp3-N donor ligands to achieve improved anticancer selectivity. Inorg. Chem. 2023, 62, 15118–15137.
  65. Sadique, S.; Baqer, A.A.; Salman, A.W.; Iqbal, M.A.; Kadim, M.M.; Jamil, F.; Majeed, A.; Manahil, S.; Altaf, A. Ruthenium complexes for breast cancer therapy. Rev. Inorg. Chem. 2023, in press.
  66. Skoczynska, A.; Lewinski, A.; Pokora, M.; Paneth, P.; Budzisz, E. An overview of the potential medicinal and pharmaceutical properties of Ru (II)/(III) complexes. Int. J. Mol. Sci. 2023, 24, 9512.
  67. Li, W.; Li, S.; Xu, G.; Man, X.; Yang, T.; Zhang, Z.; Liang, H.; Yang, F. Developing a ruthenium(III) complex to trigger gasdermin E-mediated pyroptosis and an immune response based on decitabine and liposomes: Targeting inhibition of gastric tumor growth and metastasis. J. Med. Chem. 2023, 66, 13072–13085.
  68. Lee, S.Y.; Kim, C.Y.; Nam, T.G. Ruthenium complexes as anticancer agents: A brief history and perspectives. Drug. Des. Dev. Ther. 2020, 14, 5375–5392.
  69. Kenny, R.G.; Marmion, C.J. Toward multi-targeted platinum and ruthenium drugs—A new paradigm in cancer drug treatment regimens? Chem. Rev. 2019, 119, 1058–1137.
  70. Swaminathan, S.; Deepak, R.J.; Karvembu, R. Interweaving catalysis and cancer using Ru-and Os-arene complexes to alter cellular redox state: A structure-activity relationship (SAR) review. Coord. Chem. Rev. 2023, 491, 215230.
  71. Borutzki, Y.; Skos, L.; Gerner, C.; Meier-Menches, S.M. Exploring the potential of metal-based candidate drugs as modulators of the cytoskeleton. ChemBioChem 2023, 24, e202300178.
  72. Toupin, N.; Herroon, M.K.; Thummel, R.P.; Turro, C.; Podgorski, I.; Gibson, H.; Kodanko, J.J. Metalloimmunotherapy with rhodium and ruthenium complexes: Targeting tumor-associated macrophages. Chem. Eur. J. 2022, 28, e202104430.
  73. Kanaoujiya, R.; Srivastava, S.; Singh, R.; Mustafa, G. Recent advances and application of ruthenium complexes in tumor malignancy. Mater. Today Proc. 2023, 72, 2822–2827.
  74. Bijelic, A.; Theiner, S.; Keppler, B.K.; Rompel, A. X-ray structure analysis of indazolium trans- (KP1019) bound to human serum albumin reveals two ruthenium binding sites and provides insights into the drug binding mechanism. J. Med. Chem. 2016, 59, 5894–5903.
  75. Neuditschko, B.; Legin, A.A.; Baier, D.; Schintlmeister, A.; Reipert, S.; Wagner, M.; Keppler, B.K.; Berger, W.; Meier-Menches, S.M.; Gerner, C. Interaction with ribosomal proteins accompanies stress induction of the anticancer metallodrug BOLD-100/KP1339 in the endoplasmic reticulum. Angew. Chem. Int. Ed. Engl. 2021, 60, 5063–5068.
  76. Alessio, E.; Messori, L. NAMI-A and KP1019/1339, two iconic ruthenium anticancer drug candidates face-to-face: A case story in medicinal inorganic chemistry. Molecules 2019, 24, 1995.
  77. Hinton, S.R.; Corpuz, E.L.; Holman, K.L.M.; Meyer, S.C. A split β-lactamase sensor for the detection of DNA modification by cisplatin and ruthenium-based chemotherapeutic drugs. J. Inorg. Biochem. 2022, 236, 111986.
  78. Rahman, K.M.M.; Giram, P.; Foster, B.A.; You, Y. Photodynamic therapy for bladder cancers, a focused review. Photochem. Photobiol. 2023, 99, 420–436.
  79. Murray, B.S.; Babak, M.V.; Hartinger, C.G.; Dyson, P.J. The Development of RAPTA Compounds for the Treatment of Tumors. Coord. Chem. Rev. 2016, 306, 86–114.
  80. Casini, A.; Gabbiani, C.; Sorrentino, F.; Rigobello, M.P.; Bindoli, A.; Geldbach, T.J.; Marrone, A.; Re, N.; Hartinger, C.G.; Dyson, P.J.; et al. Emerging Protein Targets For Anticancer Metallodrugs: Inhibition of thioredoxin reductase and cathepsin B by antitumor ruthenium(II)−arene compounds. J. Med. Chem. 2008, 51, 6773–6781.
  81. Aird, R.E.; Cummings, J.; Ritchie, A.A.; Muir, M.; Morris, R.E.; Chen, H.; Sadler, P.J.; Jodrell, D.I. In vitro and in vivo activity and cross resistance profiles of novel ruthenium (II) organometallic arene complexes in human ovarian cancer. Br. J. Cancer 2002, 86, 1652–1657.
  82. Romero-Canelon, I.; Sadler, P.J. Next-generation metal anticancer complexes: Multitargeting via redox modulation. Inorg. Chem. 2013, 52, 12276–12291.
  83. Scolaro, C.; Bergamo, A.; Brescacin, L.; Delfino, R.; Cocchietto, M.; Laurenczy, G.; Geldbach, T.J.; Sava, G.; Dyson, P.J. In vitro and in vivo evaluation of ruthenium(II)-arene PTA complexes. J. Med. Chem. 2005, 48, 4161–4171.
  84. Morris, R.E.; Aird, R.E.; Murdoch, P.D.; Chen, H.M.; Cummings, J.; Hughes, N.D.; Parsons, S.; Parkin, A.; Boyd, G.; Jodrell, D.I.; et al. Inhibition of cancer cell growth by ruthenium(II) arene complexes. J. Med. Chem. 2001, 44, 3616–3621.
  85. Habtemariam, A.; Melchart, M.; Fernandez, R.; Parsons, S.; Oswald, I.D.; Parkin, A.; Fabbiani, F.P.; Davidson, J.E.; Dawson, A.; Aird, R.E.; et al. Structure-activity relationships for cytotoxic ruthenium(II) arene complexes containing N,N-, N,O-, and O,O-chelating ligands. J. Med. Chem. 2006, 49, 6858–6868.
  86. Swaminathan, S.; Haribabu, J.; Balakrishnan, N.; Vasanthakumar, P.; Karvembu, R. Piano stool Ru(II)-arene complexes having three monodentate legs: A comprehensive review on their development as anticancer therapeutics over the past decade. Coord. Chem. Rev. 2022, 459, 214403.
  87. Hildebrandt, J.; Häfner, N.; Kritsch, D.; Görls, H.; Dürst, M.; Runnebaum, I.B.; Weigand, W. Highly cytotoxic osmium(II) compounds and their ruthenium(II) analogues targeting ovarian carcinoma cell lines and evading cisplatin resistance mechanisms. Int. J. Mol. Sci. 2022, 23, 4976.
  88. Lu, Y.; Zhu, D.; Le, Q.; Wang, Y.; Wang, W. Ruthenium-based antitumor drugs and delivery systems from monotherapy to combination therapy. Nanoscale 2022, 14, 16339–16375.
  89. Milović, E.; Janković, N.; Petronijević, J.; Joksimović, N.; Kosanić, M.; Stanojković, T.; Matić, I.; Grozdanić, N.; Klisurić, O.; Stefanović, S. Synthesis, characterization, and biological evaluation of tetrahydropyrimidines: Dual-activity and mechanism of action. Pharmaceutics 2022, 14, 2254.
  90. Xu, Y.; Wang, F.; Guo, H.; Wang, S.; Ni, S.; Zhou, Y.; Wang, Z.; Bao, H.; Wang, Y. Antitussive and anti-inflammatory dual-active agents developed from natural product lead compound 1-methylhydantoin. Molecules 2019, 24, 2355.
  91. Hegazy, G.E.; Abu-Serie, M.M.; Abo-Elela, G.M.; Ghozlan, H.; Sabry, S.A.; Soliman, N.A.; Abdel-Fattah, Y.R.R. In vitro dual (anticancer and antiviral) activity of the carotenoids produced by haloalkaliphilic archaeon Natrialba sp. M6. Sci. Rep. 2020, 10, 5986.
  92. Aldea, M.; Michot, J.-M.; Danlos, F.-X.; Ribas, A.; Soria, J.-C. Repurposing of anticancer drugs expands possibilities for antiviral and anti-inflammatory discovery in COVID-19. Cancer Discov. 2021, 11, 1336–1344.
  93. Trondl, R.; Heffeter, P.; Kowol, C.R.; Jakupec, M.A.; Berger, W.; Keppler, B.K. NKP-1339, the first ruthenium-based anticancer drug on the edge to clinical application. Chem. Sci. 2014, 5, 2925–2932.
  94. Meier-Menches, S.M.; Gerner, C.; Berger, W.; Hartinger, C.G.; Keppler, B.K. Structure-activity relationships for ruthenium and osmium anticancer agents towards clinical development. Chem. Soc. Rev. 2018, 47, 909–928.
  95. Pötsch, I.; Baier, D.; Keppler, B.K.; Berger, W. Challenges and chances in the preclinical to clinical translation of anticancer metallodrugs. RSC Metallobiol. 2019, 14, 308–347.
  96. Burris, H.A.; Bakewell, S.; Bendell, J.C.; Infante, J.; Jones, S.F.; Spigel, D.R.; Weiss, G.J.; Ramanathan, R.K.; Ogden, A.; Von Hoff, D.; et al. Safety and activity of IT-139, a ruthenium-based compound, in patients with advanced solid tumours: A First-in-human, open-label, dose-escalation phase I study with expansion cohort. ESMO Open 2016, 1, e000154.
  97. Farkas, E.; Marmion, C.J. (Eds.) Targeted Metallo-Drugs: Design, Development, and Modes of Action; CRC Press: Boca Raton, FL, USA, 2023; ISBN 9781032223308.
  98. Spratlin, J.L.; O’Kane, G.; Goodwin, R.A.; McWhirter, E.; Thompson, D.; Halani, K.; Jones, M.; Snow, M.; McAllister, E.R.; Machado, A.; et al. BOLD-100-001 (TRIO039): A phase 1b dose-escalation study of BOLD-100 in combination with FOLFOX chemotherapy in patients with advanced gastrointestinal solid cancers: Interim safety, tolerability, and efficacy. J. Clin. Oncol. 2022, 40 (Suppl. S16), 3031.
  99. Spratlin, J.; O’Kane, G.; Oh, D.Y.; Rha, S.Y.; McWhirter, E.; Elimova, E.; Kavan, P.; Choi, M.K.; Kim, D.W.; Goodwin, R.; et al. Abstract CT149: BOLD-100-001 (TRIO039): A phase 1b/2a dose-escalation study of BOLD-100 in combination with FOLFOX chemotherapy in patients with pre-treated advanced colorectal cancer: Interim efficacy, safety and tolerability analysis. Cancer Res. 2023, 83 (Suppl. S8), CT149.
  100. Park, B.J.; Raha, P.; Pankovich, J.; Bazett, M. Utilization of cancer cell line screening to elucidate the anticancer activity and biological pathways related to the ruthenium-based therapeutic BOLD-100. Cancers 2022, 15, 28.
  101. Labach, D.S.; Kohio, H.P.; Tse, E.A.; Paparisto, E.; Friesen, N.J.; Pankovich, J.; Bazett, M.; Barr, S.D. The metallodrug BOLD-100 is a potent inhibitor of SARS-CoV-2 replication and has broad-acting antiviral activity. Biomolecules 2023, 13, 1095.
  102. Bakewell, S.; Conde, I.; Fallah, Y.; McCoy, M.; Jin, L.; Shajahan-Haq, A.N. Inhibition of DNA repair pathways and induction of ROS are potential mechanisms of action of the small molecule inhibitor BOLD-100 in breast cancer. Cancers 2020, 12, 2647.
  103. Flocke, L.S.; Trondl, R.; Jakupec, M.A.; Keppler, B.K. Molecular mode of action of NKP-1339—A clinically investigated ruthenium-based drug—Involves ER- and ROS-related effects in colon carcinoma cell lines. Investig. New Drugs 2016, 34, 261–268.
  104. Schoenhacker-Alte, B.; Mohr, T.; Pirker, C.; Kryeziu, K.; Kuhn, P.S.; Buck, A.; Hofmann, T.; Gerner, C.; Hermann, G.; Koellensperger, G.; et al. Sensitivity towards the GRP78 inhibitor KP1339/IT-139 is characterized by apoptosis induction via caspase 8 upon disruption of ER homeostasis. Cancer Lett. 2017, 404, 79–88.
  105. Carlos, A.J.; Ha, D.P.; Yeh, D.W.; Van Krieken, R.; Tseng, C.C.; Zhang, P.; Gill, P.; Machida, K.; Lee, A.S. The chaperone GRP78 is a host auxiliary factor for SARS-CoV-2 and GRP78 depleting antibody blocks viral entry and infection. J. Biol. Chem. 2021, 296, 100759.
  106. Wernitznig, D.; Kiakos, K.; Del Favero, G.; Harrer, N.; Machat, H.; Osswald, A.; Jakupec, M.A.; Wernitznig, A.; Sommergruber, W.; Keppler, B.K. First-in-class ruthenium anticancer drug (KP1339/IT-139) induces an immunogenic cell death signature in colorectal spheroids in vitro. Metallomics 2019, 11, 1044–1048.
  107. Mucke, H.A. Patent highlights October–November 2021. Pharm. Pat. Anal. 2022, 11, 37–44.
  108. Ceramella, J.; Iacopetta, D.; Sinicropi, M.S.; Andreu, I.; Mariconda, A.; Saturnino, C.; Giuzio, F.; Longo, P.; Aquaro, S.; Catalano, A. Drugs for COVID-19: An update. Molecules 2022, 27, 8562.
  109. Lohitesh, K.; Chowdhury, R.; Mukherjee, S. Resistance a major hindrance to chemotherapy in hepatocellular carcinoma: An insight. Cancer Cell Int. 2018, 18, 44.
  110. Baier, D.; Schoenhacker-Alte, B.; Rusz, M.; Pirker, C.; Mohr, T.; Mendrina, T.; Kirchhofer, D.; Meier-Menches, S.M.; Hohenwallner, K.; Schaier, M.; et al. The anticancer ruthenium compound BOLD-100 targets glycolysis and generates a metabolic vulnerability towards glucose deprivation. Pharmaceutics 2022, 14, 238.
  111. Jang, M.; Kim, S.S.; Lee, J. Cancer cell metabolism: Implications for therapeutic targets. Exp. Mol. Med. 2013, 45, e45.
  112. Liberti, M.V.; Locasale, J.W. The Warburg Effect: How Does it Benefit Cancer Cells? Trends Biochem. Sci. 2016, 41, 211–218.
  113. Baier, D.; Mendrina, T.; Schoenhacker-Alte, B.; Pirker, C.; Mohr, T.; Rusz, M.; Regner, B.; Schaier, M.; Sgarioto, N.; Raynal, N.J.M.; et al. The lipid metabolism as target and modulator of BOLD-100 anticancer activity: Crosstalk with histone acetylation. Adv. Sci. 2023, 10, 2301939.
  114. Intravesical Photodynamic Therapy (PDT) in BCG Refractory/Intolerant Non-Muscle Invasive Bladder Cancer (NMIBC) Patients. Available online: https://clinicaltrials.gov/ct2/show/NCT03945162 (accessed on 11 October 2023).
  115. Kulkarni, G.; Richards, K.; Black, P.C.; Rendon, R.; Chin, J.; Shore, N.; Jayram, G.; Kramolowsky, E.; Saltzstein, D.; Agarwal, A.; et al. MP63-01 an interim analysis of a phase ii clinical study of intravesical photodynamic therapy in patients with bcg-unresponsive non-muscle invasive bladder cancer (NMIBC) carcinoma in-situ (CIS). J. Urol. 2023, 209 (Suppl. S4), e871.
  116. Chen, Q.; Ramu, V.; Aydar, Y.; Groenewoud, A.; Zhou, X.-Q.; Jager, M.J.; Cole, H.; Cameron, C.G.; McFarland, S.A.; Bonnet, S.; et al. TLD1433 photosensitizer inhibits conjunctival melanoma cells in zebrafish ectopic and orthotopic tumour models. Cancers 2020, 12, 587.
  117. Harada, Y.; Murayama, Y.; Takamatsu, T.; Otsuji, E.; Tanaka, H. 5-Aminolevulinic acid-induced protoporphyrin ix fluorescence imaging for tumor detection: Recent advances and challenges. Int. J. Mol. Sci. 2022, 23, 6478.
  118. Karges, J. Clinical development of metal complexes as photosensitizers for photodynamic therapy of cancer. Angew. Chem. Int. Ed. 2022, 61, e202112236.
  119. Swaminathan, S.; Karvembu, R. Dichloro Ru(II)-p-cymene-1,3,5-triaza-7-phosphaadamantane (RAPTA-C): A case study. ACS Pharm. Translat. Sci. 2023, 6, 982–996.
  120. Bashir, M.; Mantoo, I.A.; Arjmand, F.; Tabassum, S.; Yousuf, I. An overview of advancement of organoruthenium(II) complexes as prospective anticancer agents. Coord. Chem. Rev. 2023, 487, 215169.
  121. Rausch, M.; Dyson, P.J.; Nowak-Sliwinska, P. Recent considerations in the application of RAPTA-C for cancer treatment and perspectives for its combination with immunotherapies. Adv. Ther. 2019, 2, 1900042.
  122. Weiss, A.; Ding, X.; van Beijnum, J.R.; Wong, I.; Wong, T.J.; Berndsen, R.H.; Dormond, O.; Dallinga, M.; Shen, L.; Schlingemann, R.O.; et al. Rapid optimization of drug combinations for the optimal angiostatic treatment of cancer. Angiogenesis 2015, 18, 233–244.
  123. Coverdale, J.P.C.; Laroiya-McCarron, T.; Isolda Romero-Canelón, I. Designing ruthenium anticancer drugs: What have we learnt from the key drug candidates? Inorganics 2019, 7, 31.
  124. Weiss, A.; Berndsen, R.H.; Ding, X.; Ho, C.M.; Dyson, P.J.; Van Den Bergh, H.; Griffioen, A.W.; Nowak-Sliwinska, P. A streamlined search technology for identification of synergistic drug combinations. Sci. Rep. 2015, 5, 14508.
  125. Berndsen, R.H.; Weiss, A.; Abdul, U.K.; Wong, T.J.; Meraldi, P.; Griffioen, A.W.; Dyson, P.J.; Nowak-Sliwinska, P. Combination of ruthenium(II)-arene complex (RAPTA-C) and the epidermal growth factor receptor inhibitor erlotinib results in efficient angiostatic and antitumor activity. Sci. Rep. 2017, 7, 43005.
  126. Weiss, A.; Berndsen, R.H.; Dubois, M.; Müller, C.; Schibli, R.; Griffioen, A.W.; Dyson, P.J.; Nowak-Sliwinska, P. In vivo anti-tumor activity of the organometallic ruthenium(II)-arene complex (RAPTA-C) in human ovarian and colorectal carcinomas. Chem. Sci. 2014, 5, 4742–4748.
  127. Lu, M.; Wang, S.; Khine, Y.Y.; Hong, Y.; Zheng, J.; Lu, H.; Stenzel, M.H. Dual drug delivery system of RAPTA-C and paclitaxel based on fructose coated nanoparticles for metastatic cancer treatment. Biochem. Biophys. Res. Commun. 2023, 640, 134–141.
  128. Marzo, T.; Messori, L. A Role for metal-based drugs in fighting COVID-19 infection? The Case of Auranofin. ACS Med. Chem. Lett. 2020, 11, 1067–1068.
  129. De Paiva, R.E.F.; Marçal Neto, A.; Santos, I.A.; Jardim, A.C.G.; Corbi, P.P.; Bergamini, F.R.G. What is holding back the development of antiviral metallodrugs? A literature overview and implications for SARS-CoV-2 therapeutics and future viral outbreaks. Dalton Trans. 2020, 49, 16004–16033.
  130. Chuong, C.; DuChane, C.M.; Webb, E.M.; Rai, P.; Marano, J.M.; Bernier, C.M.; Merola, J.S.; Weger-Lucarelli, J. Noble metal organometallic complexes display antiviral activity against SARS-CoV-2. Viruses 2021, 13, 980.
  131. El-Lateef, H.M.A.; El-Dabea, T.; Khalaf, M.M.; Abu-Dief, A.M. Development of metal complexes for treatment of coronaviruses. Int. J. Mol. Sci. 2022, 23, 6418.
  132. Kojima, S.; Hasegawa, T.; Yonemura, T.; Sasaki, K.; Yamamoto, K.; Makimura, Y.; Takahashi, T.; Suzuki, T.; Suzuki, Y.; Kobayashi, K. Ruthenium complexes carrying a disialo complex-type oligosaccharide: Enzymatic synthesis and its application to a luminescent probe to detect influenza viruses. Chem. Commun. 2003, 11, 1250–1251.
  133. Wong, E.L.-M.; Sun, R.W.-Y.; Chung, N.P.-Y.; Lin, C.-L.S.; Zhu, N.; Che, C.-M. A mixed-valent ruthenium−oxo oxalato cluster Na7 with potent anti-HIV activities. J. Am. Chem. Soc. 2006, 128, 4938–4939.
  134. Gil-Moles, M.; Türck, S.; Basu, U.; Pettenuzzo, A.; Bhattacharya, S.; Rajan, A.; Ma, X.; Büssing, R.; Wölker, J.; Burmeister, H.; et al. Metallodrug profiling against SARS-CoV-2 target proteins identifies highly potent inhibitors of the S/ACE2 interaction and the Papain-like Protease PLpro. Chem. Eur. J. 2021, 27, 17928–17940.
  135. Janković, N.; Milović, E.; Jovanović, J.Đ.; Marković, Z.; Vraneš, M.; Stanojković, T.; Matić, I.; Crnogorac, M.Đ.; Klisurić, O.; Cvetinov, M. A new class of half-sandwich ruthenium complexes containing Biginelli hybrids: Anticancer and anti-SARS-CoV-2 activities. Chem. Biol. Interact. 2022, 363, 110025.
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Assunta D’Amato
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Annaluisa Mariconda
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Domenico Iacopetta
,
Jessica Ceramella
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Alessia Catalano
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Maria Stefania Sinicropi
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Pasquale Longo
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