Startseite Naturwissenschaften In-vitro anticancer profile of recent ruthenium complexes against liver cancer
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

In-vitro anticancer profile of recent ruthenium complexes against liver cancer

  • Khurram Shahzad , Mohammad Asad , Abdullah M. Asiri , Muhammad Irfan und Muhammad Adnan Iqbal ORCID logo EMAIL logo
Veröffentlicht/Copyright: 6. Mai 2022

Abstract

Ruthenium complexes are considered as the most favorable alternatives to traditional platinum-based cancer drugs owing to their acceptable toxicity level, selectivity, variant oxidation states and ability to treat platinum-resistant cancer cells. They have similar ligand exchange kinetics as platinum drugs but can be tailored according to our desire by ligands influence. In the current study, we illustrate the in-vitro anticancer profile of some ruthenium complexes (2016–2021) against human hepatocellular carcinoma (HepG2). The anticancer activity of ruthenium complexes is determined by comparing their IC50 values with one another and positive controls. Fortunately, some ruthenium complexes including 3, 4, 6, 14, 15, 20, 42, and 48 exhibit surpassed in-vitro anticancer profile than that of positive controls promising as potential candidates against liver cancer. We also explored the structure-activity relationship (SAR) which is a key factor in the rational designing and synthesis of new ruthenium drugs. It covers the factors affecting anticancer activity including lipophilicity, planarity, area and bulkiness, the steric influence of different ligands, and electronic effects induced by ligands, stability, aqueous solubility and bioavailability to the target sites. The data reported here will provide strong support in the plausible design and synthesis of ruthenium anticancer drugs in the upcoming days.


Corresponding author: Muhammad Adnan Iqbal, Department of Chemistry, University of Agriculture, Faisalabad, 38000, Pakistan; and Organometallic and Coordination Chemistry Laboratory, University of Agriculture, Faisalabad, 38000, Pakistan, E-mail:

Award Identifier / Grant number: IFPRP: 450-130-1442

Acknowledgements

This research work was funded by Institutional Fund Projects under grant no. (IFPRP: 450-130-1442). Therefore, authors gratefully acknowledge technical and financial support from the Ministry of Education and King Abdulaziz University, DSR, Jeddah, Saudi Arabia.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This study was funded by King Abdulaziz University and the Grant IFPRP: 450-130-1442.

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

References

Alsaeedi, M. S.; Babgi, B. A.; Abdellattif, M. H.; Jedidi, A.; Humphrey, M. G.; Hussien, M. A. DNA-binding capabilities and anticancer activities of ruthenium (II) cymene complexes with (Poly) cyclic aromatic diamine ligands. Molecules 2021, 26(1), 76.10.3390/molecules26010076Suche in Google Scholar PubMed PubMed Central

Bosch, F. X.; Ribes, J.; Díaz, M.; Cléries, R. Primary liver cancer: worldwide incidence and trends. Gastroenterology 2004, 127(5, Suppl. 1), S5–S16. https://doi.org/10.1053/j.gastro.2004.09.011.Suche in Google Scholar PubMed

Bailleux, C.; Eberst, L.; Bachelot, T. Treatment strategies for breast cancer brain metastases. Br. J. Cancer 2021, 124(1), 142–155. https://doi.org/10.1038/s41416-020-01175-y.Suche in Google Scholar PubMed PubMed Central

Bergamo, A.; Sava, G. Ruthenium anticancer compounds: myths and realities of the emerging metal-based drugs. Dalton Trans. 2011, 40(31), 7817–7823.https://doi.org/10.1039/c0dt01816c.Suche in Google Scholar PubMed

Bratsos, I.; Jedner, S.; Gianferrara, T.; Alessio, E. Ruthenium anticancer compounds: challenges and expectations. CHIMIA Int. J. Chem. 2007, 61(11), 692–697. https://doi.org/10.2533/chimia.2007.692.Suche in Google Scholar

Bergamo, A.; Gaiddon, C.; Schellens, J. H. M.; Beijnen, J. H.; Sava, G. Approaching tumour therapy beyond platinum drugs: status of the art and perspectives of ruthenium drug candidates. J. Inorg. Biochem. 2012, 106(1), 90–99.https://doi.org/10.1016/j.jinorgbio.2011.09.030.Suche in Google Scholar PubMed

Batchelor, L. K.; Păunescu, E.; Soudani, M. N.; Scopelliti, R.; Dyson, P. J. Influence of the linker length on the cytotoxicity of homobinuclear ruthenium (II) and gold (I) complexes. Inorg. Chem. 2017, 56(16), 9617–9633.https://doi.org/10.1021/acs.inorgchem.7b01082.Suche in Google Scholar PubMed

Brabec, V.; Nováková, O. DNA binding mode of ruthenium complexes and relationship to tumor cell toxicity. Drug Resist. Updates 2006, 9(3), 111–122.https://doi.org/10.1016/j.drup.2006.05.002.Suche in Google Scholar PubMed

Cervello, M.; Bachvarov, D.; Lampiasi, N.; Cusimano, A.; Azzolina, A.; McCubrey, J. A.; Montalto, G. Molecular mechanisms of sorafenib action in liver cancer cells. Cell Cycle 2012, 11(15), 2843–2855. https://doi.org/10.4161/cc.21193.Suche in Google Scholar PubMed

Coverdale, J. P.; Laroiya-McCarron, T.; Romero-Canelón, I. Designing ruthenium anticancer drugs: what have we learnt from the key drug candidates? INORGA 2019, 7(3), 31.https://doi.org/10.3390/inorganics7030031.Suche in Google Scholar

Clarke, M. J. Ruthenium metallopharmaceuticals. Coord. Chem. Rev. 2002, 232(1-2), 69–93.https://doi.org/10.1016/s0010-8545(02)00025-5.Suche in Google Scholar

de Carvalho, N. C.; Neves, S. P.; Dias, R. B.; Valverde, L. D. F.; Sales, C. B.; Rocha, C. A.; Soares, M. B.; dos Santos, E. R.; Oliveira, R. M.; Carlos, R. M. A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway. Cell Death Dis. 2018, 9(2), 79.https://doi.org/10.1038/s41419-017-0104-6.Suche in Google Scholar PubMed PubMed Central

Chen, J.; Zhang, Y.; Li, G.; Peng, F.; Jie, X.; She, J.; Dongye, G.; Zou, Z.; Rong, S.; Chen, L. Cytotoxicity in vitro, cellular uptake, localization and apoptotic mechanism studies induced by ruthenium (II) complex. JBIC J. Biol. Inorg. Chem. 2018, 23(2), 261–275.https://doi.org/10.1007/s00775-017-1528-2.Suche in Google Scholar PubMed

Carlos Lima, J.; Rodriguez, L. Phosphine-gold (I) compounds as anticancer agents: general description and mechanisms of action. Anti Cancer Agents Med. Chem. 2011, 11(10), 921–928.https://doi.org/10.2174/187152011797927670.Suche in Google Scholar PubMed

Chen, L.; Li, G.; Peng, F.; Jie, X.; Dongye, G.; Cai, K.; Feng, R.; Li, B.; Zeng, Q.; Lun, K. The induction of autophagy against mitochondria-mediated apoptosis in lung cancer cells by a ruthenium (II) imidazole complex. Oncotarget 2016, 7(49), 80716.https://doi.org/10.18632/oncotarget.13032.Suche in Google Scholar PubMed PubMed Central

Corte-Rodríguez, M.; Espina, M.; Sierra, L.; Blanco, E.; Ames, T.; Montes-Bayón, M.; Sanz-Medel, A. Quantitative evaluation of cellular uptake, DNA incorporation and adduct formation in cisplatin sensitive and resistant cell lines: comparison of different Pt-containing drugs. Biochem. Pharmacol. 2015, 98(1), 69–77.10.1016/j.bcp.2015.08.112Suche in Google Scholar PubMed

Chen, J.-C.; Zhang, Y.; Jie, X.-M.; She, J.; Dongye, G.-Z.; Zhong, Y.; Deng, Y.-Y.; Wang, J.; Guo, B.-Y.; Chen, L.-M. Ruthenium (II) salicylate complexes inducing ROS-mediated apoptosis by targeting thioredoxin reductase. J. Inorg. Biochem. 2019, 193, 112–123.https://doi.org/10.1016/j.jinorgbio.2019.01.011.Suche in Google Scholar PubMed

Côrte-Real, L.; Teixeira, R. G.; Gírio, P.; Comsa, E.; Moreno, A.; Nasr, R.; Baubichon-Cortay, H.; Avecilla, F.; Marques, F.; Robalo, M. P. Methyl-cyclopentadienyl ruthenium compounds with 2, 2′-bipyridine derivatives display strong anticancer activity and multidrug resistance potential. Inorg. Chem. 2018, 57(8), 4629–4639.10.1021/acs.inorgchem.8b00358Suche in Google Scholar PubMed

Deng, Z.; Gao, P.; Yu, L.; Ma, B.; You, Y.; Chan, L.; Mei, C.; Chen, T. Ruthenium complexes with phenylterpyridine derivatives target cell membrane and trigger death receptors-mediated apoptosis in cancer cells. Biomaterials 2017, 129, 111–126.https://doi.org/10.1016/j.biomaterials.2017.03.017.Suche in Google Scholar PubMed

Dredge, K.; Hammond, E.; Handley, P.; Gonda, T.; Smith, M.; Vincent, C.; Brandt, R.; Ferro, V.; Bytheway, I. PG545, a dual heparanase and angiogenesis inhibitor, induces potent anti-tumour and anti-metastatic efficacy in preclinical models. Br. J. Cancer 2011, 104(4), 635–642.https://doi.org/10.1038/bjc.2011.11.Suche in Google Scholar PubMed PubMed Central

Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D. M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 2015, 136(5), E359–E386.https://doi.org/10.1002/ijc.29210.Suche in Google Scholar PubMed

Ferlay, J.; Colombet, M.; Soerjomataram, I.; Parkin, D. M.; Piñeros, M.; Znaor, A.; Bray, F. Cancer statistics for the year 2020: an overview. Int. J. Cancer 2021, 149(4), 778–789. https://doi.org/10.1002/ijc.33588.Suche in Google Scholar PubMed

Franzblau, S. G.; Witzig, R. S.; McLaughlin, J. C.; Torres, P.; Madico, G.; Hernandez, A.; Degnan, M. T.; Cook, M. B.; Quenzer, V. K.; Ferguson, R. M. Rapid, low-technology MIC determination with clinical Mycobacterium tuberculosis isolates by using the microplate Alamar Blue assay. J. Clin. Microbiol. 1998, 36(2), 362–366.https://doi.org/10.1128/jcm.36.2.362-366.1998.Suche in Google Scholar

Golbaghi, G.; Castonguay, A. Rationally designed ruthenium complexes for breast cancer therapy. Molecules 2020, 25(2), 265.https://doi.org/10.3390/molecules25020265.Suche in Google Scholar PubMed PubMed Central

De Grandis, R. A.; Dos Santos, P. W. D. S.; de Oliveira, K. M.; Machado, A. R. T.; Aissa, A. F.; Batista, A. A.; Antunes, L. M. G.; Pavan, F. R. Novel lawsone-containing ruthenium (II) complexes: synthesis, characterization and anticancer activity on 2D and 3D spheroid models of prostate cancer cells. Bioorg. Chem. 2019, 85, 455–468.https://doi.org/10.1016/j.bioorg.2019.02.010.Suche in Google Scholar PubMed

Groessl, M.; Hartinger, C. G.; Dyson, P. J.; Keppler, B. K. CZE–ICP-MS as a tool for studying the hydrolysis of ruthenium anticancer drug candidates and their reactivity towards the DNA model compound dGMP. J. Inorg. Biochem. 2008, 102(5-6), 1060–1065.https://doi.org/10.1016/j.jinorgbio.2007.11.018.Suche in Google Scholar PubMed

Hosseini, F. S.; Falahati-Pour, S. K.; Hajizadeh, M. R.; Khoshdel, A.; Mirzaei, M. R.; Ahmadirad, H.; Behroozi, R.; Jafari, N.; Mahmoodi, M. Persian shallot, Allium hirtifolium Boiss, induced apoptosis in human hepatocellular carcinoma cells. Cytotechnology 2017, 69(4), 551–563.https://doi.org/10.1007/s10616-017-0093-4.Suche in Google Scholar PubMed PubMed Central

Harun, S. N.; Ahmad, H.; Lim, H. N.; Chia, S. L.; Gill, M. R. Synthesis and optimization of mesoporous silica nanoparticles for ruthenium polypyridyl drug delivery. Pharmaceutics 2021, 13(2), 150.https://doi.org/10.3390/pharmaceutics13020150.Suche in Google Scholar PubMed PubMed Central

Haghdoost, M.; Golbaghi, G.; Létourneau, M.; Patten, S. A.; Castonguay, A. Lipophilicity-antiproliferative activity relationship study leads to the preparation of a ruthenium (II) arene complex with considerable in vitro cytotoxicity against cancer cells and a lower in vivo toxicity in zebrafish embryos than clinically approved cis-platin. Eur. J. Med. Chem. 2017, 132, 282–293.https://doi.org/10.1016/j.ejmech.2017.03.029.Suche in Google Scholar PubMed

Huang, H.; Zhang, P.; Chen, Y.; Qiu, K.; Jin, C.; Ji, L.; Chao, H. Synthesis, characterization and biological evaluation of labile intercalative ruthenium (II) complexes for anticancer drug screening. Dalton Trans. 2016, 45(33), 13135–13145.https://doi.org/10.1039/c6dt01270a.Suche in Google Scholar PubMed

Irfan, M.; Rehman, R.; Razali, M. R.; Iqbal, M. A. Organotellurium compounds: an overview of synthetic methodologies. Rev. Inorg. Chem. 2020, 1, published ahead of print; https://doi.org/10.1515/revic-2020-0006.Suche in Google Scholar

Jeon, J.; Lee, S.; Kim, H.; Kang, H.; Youn, H.; Jo, S.; Youn, B.; Kim, H. Y. Revisiting platinum-based anticancer drugs to overcome gliomas. Int. J. Mol. Sci. 2021, 22(10), 5111. https://doi.org/10.3390/ijms22105111.Suche in Google Scholar PubMed PubMed Central

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(2), 1058–1137.https://doi.org/10.1021/acs.chemrev.8b00271.Suche in Google Scholar PubMed

Karmakar, J.; Nandy, P.; Das, S.; Bhattacharya, D.; Karmakar, P.; Bhattacharya, S. Utilization of Guanidine-based ancillary ligands in arene–ruthenium complexes for selective cytotoxicity. ACS Omega 2021, 6(12), 8226–8238.https://doi.org/10.1021/acsomega.0c06265.Suche in Google Scholar PubMed PubMed Central

Ke, N.; Xi, B.; Ye, P.; Xu, W.; Zheng, M.; Mao, L.; Wu, M.-J.; Zhu, J.; Wu, J.; Zhang, W. Screening and identification of small molecule compounds perturbing mitosis using time-dependent cellular response profiles. Anal. Chem. 2010, 82(15), 6495–6503.https://doi.org/10.1021/ac1007877.Suche in Google Scholar PubMed

Li, X.; Ramadori, P.; Pfister, D.; Seehawer, M.; Zender, L.; Heikenwalder, M. The immunological and metabolic landscape in primary and metastatic liver cancer. Nat. Rev. Cancer 2021, 21(9), 541–557.https://doi.org/10.1038/s41568-021-00383-9.Suche in Google Scholar PubMed

Levina, A.; Mitra, A.; Lay, P. A. Recent developments in ruthenium anticancer drugs. Metallomics 2009, 1(6), 458–470. https://doi.org/10.1039/b904071d.Suche in Google Scholar PubMed

Li, F.; Collins, J. G.; Keene, F. R. Ruthenium complexes as antimicrobial agents. Chem. Soc. Rev. 2015, 44(8), 2529–2542. https://doi.org/10.1039/c4cs00343h.Suche in Google Scholar PubMed

Li, Y.; Wu, Q.; Yu, G.; Li, L.; Zhao, X.; Huang, X.; Mei, W. Polypyridyl Ruthenium (II) complex-induced mitochondrial membrane potential dissipation activates DNA damage-mediated apoptosis to inhibit liver cancer. Eur. J. Med. Chem. 2019, 164, 282–291.https://doi.org/10.1016/j.ejmech.2018.12.041.Suche in Google Scholar PubMed

Lang, X.-X.; Yu, Q.-Q.; Li, H.-Y.; Luo, Y.; Yu, X.-F.; Wang, H.-J.; Wang, M.-Q. Identification of a non-planar imidazole-cored small molecule for selective telomeric G4 DNA targeting. Dyes Pigments 2022, 197, 109901.https://doi.org/10.1016/j.dyepig.2021.109901.Suche in Google Scholar

Liu, X.; Huang, J.; Tang, Y.; Shen, Y.; Lu, J. Topoisomerase I inhibitory and photocleavage activity of non‐dppz DNA ‘light switches’ based on ruthenium complexes containing nitro group. Appl. Organomet. Chem. 2018, 32(8), e4423.https://doi.org/10.1002/aoc.4423.Suche in Google Scholar

Lu, Y.; Shen, T.; Yang, H.; Gu, W. Ruthenium complexes induce HepG2 human hepatocellular carcinoma cell apoptosis and inhibit cell migration and invasion through regulation of the Nrf2 pathway. Int. J. Mol. Sci. 2016, 17(5), 775.https://doi.org/10.3390/ijms17050775.Suche in Google Scholar PubMed PubMed Central

Lagunin, A. A.; Romanova, M. A.; Zadorozhny, A. D.; Kurilenko, N. S.; Shilov, B. V.; Pogodin, P. V.; Ivanov, S. M.; Filimonov, D. A.; Poroikov, V. V. Comparison of quantitative and qualitative (Q) SAR models created for the prediction of Ki and IC50 values of antitarget inhibitors. Front. Pharmacol. 2018, 9, 1136.https://doi.org/10.3389/fphar.2018.01136.Suche in Google Scholar PubMed PubMed Central

Motswainyana, W. M.; Ajibade, P. A. Anticancer activities of mononuclear ruthenium (II) coordination complexes. Adv. Chem. 2015, 2015, 1–21,.https://doi.org/10.1155/2015/859730.Suche in Google Scholar

Maschke, M.; Alborzinia, H.; Lieb, M.; Wölfl, S.; Metzler‐Nolte, N. Structure–activity relationship of Trifluoromethyl‐containing Metallocenes: electrochemistry, lipophilicity, cytotoxicity, and ROS production. ChemMedChem 2014, 9(6), 1188–1194.https://doi.org/10.1002/cmdc.201402001.Suche in Google Scholar PubMed

Mårtensson, A. K.; Lincoln, P. Effects of methyl substitution on DNA binding enthalpies of enantiopure Ru (phenanthroline) 2 dipyridophenazine 2+ complexes. Phys. Chem. Chem. Phys. 2018, 20(16), 11336–11341.10.1039/C8CP01151FSuche in Google Scholar PubMed

Morak-Młodawska, B.; Pluta, K.; Jeleń, M. Evaluation of the lipophilicity of new anticancer 1, 2, 3-Triazole-dipyridothiazine hybrids using RP TLC and different computational methods. Processes 2020, 8(7), 858.10.3390/pr8070858Suche in Google Scholar

Mohan, N.; Muthumari, S.; Ramesh, R. Synthesis, structure and anticancer activity of (η6-benzene) ruthenium (II) complexes containing aroylhydrazone ligands. J. Organomet. Chem. 2016, 807, 45–51.https://doi.org/10.1016/j.jorganchem.2016.01.033.Suche in Google Scholar

Marker, S. C.; MacMillan, S. N.; Zipfel, W. R.; Li, Z.; Ford, P. C.; Wilson, J. J. Photoactivated in vitro anticancer activity of rhenium (I) tricarbonyl complexes bearing water-soluble phosphines. Inorg. Chem. 2018, 57(3), 1311–1331.https://doi.org/10.1021/acs.inorgchem.7b02747.Suche in Google Scholar PubMed PubMed Central

Nagy, E.; Liu, Y.; Prentice, K. J.; Sloop, K. W.; Sanders, P. E.; Batchuluun, B.; Hammond, C. D.; Wheeler, M. B.; Durham, T. B. Synthesis and characterization of urofuranoic acids: in vivo metabolism of 2-(2-Carboxyethyl)-4-methyl-5-propylfuran-3-carboxylic acid (CMPF) and effects on in vitro insulin secretion. J. Med. Chem. 2017, 60(5), 1860–1875.https://doi.org/10.1021/acs.jmedchem.6b01668.Suche in Google Scholar PubMed

Novakova, O.; Kasparkova, J.; Vrana, O.; van Vliet, P. M.; Reedijk, J.; Brabec, V. Correlation between cytotoxicity and DNA binding of polypyridyl ruthenium complexes. Biochemistry 1995, 34(38), 12369–12378.https://doi.org/10.1021/bi00038a034.Suche in Google Scholar PubMed

Nepali, K.; Lee, H.-Y.; Liou, J.-P. Nitro-group-containing drugs. J. Med. Chem. 2018, 62(6), 2851–2893. https://doi.org/10.1021/acs.jmedchem.8b00147.Suche in Google Scholar PubMed

Oun, R.; Moussa, Y. E.; Wheate, N. J. The side effects of platinum-based chemotherapy drugs: a review for chemists. Dalton Trans. 2018, 47(19), 6645–6653.https://doi.org/10.1039/c8dt00838h.Suche in Google Scholar PubMed

Oldfield, S. P.; Hall, M. D.; Platts, J. A. Calculation of lipophilicity of a large, diverse dataset of anticancer platinum complexes and the relation to cellular uptake. J. Med. Chem. 2007, 50(21), 5227–5237.https://doi.org/10.1021/jm0708275.Suche in Google Scholar PubMed

Piccolo, M.; Ferraro, M. G.; Raucci, F.; Riccardi, C.; Saviano, A.; Russo Krauss, I.; Trifuoggi, M.; Caraglia, M.; Paduano, L.; Montesarchio, D. Safety and efficacy evaluation in vivo of a cationic nucleolipid nanosystem for the nanodelivery of a ruthenium (III) complex with superior anticancer bioactivity. Cancers 2021, 13(20), 5164.https://doi.org/10.3390/cancers13205164.Suche in Google Scholar PubMed PubMed Central

Popolin, P. C.; Cominetti, M. R. A review of ruthenium complexes activities on breast cancer cells. Mini Rev. Med. Chem. 2017, 17(15), 1435–1441.https://doi.org/10.2174/1389557517666170206151218.Suche in Google Scholar PubMed

Reedijk, J. Platinum anticancer coordination compounds: study of DNA binding inspires new drug design. Eur. J. Inorg. Chem. 2009, 2009(10), 1303–1312.https://doi.org/10.1002/ejic.200900054.Suche in Google Scholar

van Rijt, S. H.; Sadler, P. J. Current applications and future potential for bioinorganic chemistry in the development of anticancer drugs. Drug Discov. Today 2009, 14(23), 1089–1097.https://doi.org/10.1016/j.drudis.2009.09.003.Suche in Google Scholar PubMed PubMed Central

Ruiz, J.; Rodriguez, V.; Cutillas, N.; Espinosa, A.; Hannon, M. J. A potent ruthenium (II) antitumor complex bearing a lipophilic levonorgestrel group. Inorg. Chem. 2011, 50(18), 9164–9171.https://doi.org/10.1021/ic201388n.Suche in Google Scholar PubMed

Reedijk, B. J. Metal-ligand exchange kinetics in platinum and ruthenium complexes. Platin. Met. Rev. 2008, 52(1), 2–11. https://doi.org/10.1595/147106708x255987.Suche in Google Scholar

Ren, F.; Ji, P. Recent advances in the application of metal–organic frameworks for polymerization and oligomerization reactions. Catalysts 2020, 10(12), 1441.https://doi.org/10.3390/catal10121441.Suche in Google Scholar

Roy, S.; Hagen, K. D.; Maheswari, P. U.; Lutz, M.; Spek, A. L.; Reedijk, J.; van Wezel, G. P. Phenanthroline derivatives with improved selectivity as DNA‐targeting anticancer or antimicrobial drugs. ChemMedChem: Chem. Enabl. Drug Discov. 2008, 3(9), 1427–1434.https://doi.org/10.1002/cmdc.200800097.Suche in Google Scholar PubMed

Shahzad, K.; Majid, A. S. A.; Khan, M.; Iqbal, M. A.; Ali, A. Recent advances in the synthesis of (99mTechnetium) based radio-pharmaceuticals. Rev. Inorg. Chem. 2021, 41(3), 151–198.10.1515/revic-2020-0021Suche in Google Scholar

Silvestri, S.; Cirilli, I.; Marcheggiani, F.; Dludla, P.; Lupidi, G.; Pettinari, R.; Marchetti, F.; Di Nicola, C.; Falcioni, G.; Marchini, C. Evaluation of anticancer role of a novel ruthenium (II)-based compound compared with NAMI-A and cisplatin in impairing mitochondrial functionality and promoting oxidative stress in triple negative breast cancer models. Mitochondrion 2021, 56, 25–34. https://doi.org/10.1016/j.mito.2020.11.004.Suche in Google Scholar PubMed

Southam, H. M.; Butler, J. A.; Chapman, J. A.; Poole, R. K. The microbiology of ruthenium complexes. Adv. Microb. Physiol. 2017, 71, 1–96. https://doi.org/10.1016/bs.ampbs.2017.03.001.Suche in Google Scholar PubMed

Subarkhan, M. K. M.; Ramesh, R. Ruthenium (II) arene complexes containing benzhydrazone ligands: synthesis, structure and antiproliferative activity. Inorg. Chem. Front. 2016, 3(10), 1245–1255.https://doi.org/10.1039/c6qi00197a.Suche in Google Scholar

Savić, N. D.; Milivojevic, D. R.; Glišić, B. Đ.; Ilic-Tomic, T.; Veselinovic, J.; Pavic, A.; Vasiljevic, B.; Nikodinovic-Runic, J.; Djuran, M. I. A comparative antimicrobial and toxicological study of gold (III) and silver (I) complexes with aromatic nitrogen-containing heterocycles: synergistic activity and improved selectivity index of Au (III)/Ag (I) complexes mixture. RSC Adv. 2016, 6(16), 13193–13206.10.1039/C5RA26002GSuche in Google Scholar

Shad, H.; Hussain, A.; Shahzad, K.; Abeeha, H. G. Multi-component synthesis of novel diazoles: their characterization and biological evaluation. Arc Org Inorg Chem Sci 2018, 1(2), 107. https://doi.org/10.32474/aoics.2018.01.000107.Suche in Google Scholar

Testa, B.; Crivori, P.; Reist, M.; Carrupt, P.-A. The influence of lipophilicity on the pharmacokinetic behavior of drugs: concepts and examples. Perspect. Drug Discov. Des. 2000, 19(1), 179–211.https://doi.org/10.1023/a:1008741731244.10.1023/A:1008741731244Suche in Google Scholar

Wong, M. C. S.; Jiang, J. Y.; Goggins, W. B.; Liang, M.; Fang, Y.; Fung, F. D. H.; Leung, C.; Wang, H. H. X.; Wong, G. L. H.; Wong, V. W. S.; Chan, H. L. Y. International incidence and mortality trends of liver cancer: a global profile. Sci. Rep. 2017, 7(1), 45846. https://doi.org/10.1038/srep45846.Suche in Google Scholar PubMed PubMed Central

Wang, J.; Tao, J.; Jia, S.; Wang, M.; Jiang, H.; Du, Z. The protein-binding behavior of platinum anticancer drugs in blood revealed by mass spectrometry. Pharmaceuticals 2021, 14(2), 104.https://doi.org/10.3390/ph14020104.Suche in Google Scholar PubMed PubMed Central

Wan, D.; Tang, B.; Wang, Y.-J.; Guo, B.-H.; Yin, H.; Yi, Q.-Y.; Liu, Y.-J. Synthesis and anticancer properties of ruthenium (II) complexes as potent apoptosis inducers through mitochondrial disruption. Eur. J. Med. Chem. 2017, 139, 180–190.https://doi.org/10.1016/j.ejmech.2017.07.066.Suche in Google Scholar PubMed

Xu, Z.; Kong, D.; He, X.; Guo, L.; Ge, X.; Liu, X.; Zhang, H.; Li, J.; Yang, Y.; Liu, Z. Mitochondria-targeted half-sandwich ruthenium II diimine complexes: anticancer and antimetastasis via ROS-mediated signalling. Inorg. Chem. Front. 2018, 5(9), 2100–2105.https://doi.org/10.1039/c8qi00476e.Suche in Google Scholar

Yan, Y. K.; Melchart, M.; Habtemariam, A.; Sadler, P. J. Organometallic chemistry, biology and medicine: ruthenium arene anticancer complexes. Chem. Commun. 2005, 2005(38), 4764–4776; https://doi.org/10.1039/b508531b.Suche in Google Scholar PubMed

Yang, X.; Chen, L.; Liu, Y.; Yang, Y.; Chen, T.; Zheng, W.; Liu, J.; He, Q.-Y. Ruthenium methylimidazole complexes induced apoptosis in lung cancer A549 cells through intrinsic mitochondrial pathway. Biochimie 2012, 94(2), 345–353.https://doi.org/10.1016/j.biochi.2011.07.025.Suche in Google Scholar PubMed

Zhao, X.; Li, L.; Yu, G.; Zhang, S.; Li, Y.; Wu, Q.; Huang, X.; Mei, W. Nucleus-enriched ruthenium Polypyridine complex acts as a Potent inhibitor to suppress triple-negative breast cancer Metastasis in vivo. Comput. Struct. Biotechnol. J. 2019, 17, 21–30.https://doi.org/10.1016/j.csbj.2018.11.010.Suche in Google Scholar PubMed PubMed Central

Received: 2021-11-04
Accepted: 2022-04-19
Published Online: 2022-05-06
Published in Print: 2023-03-28

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Heruntergeladen am 10.12.2025 von https://www.degruyterbrill.com/document/doi/10.1515/revic-2021-0040/pdf
Button zum nach oben scrollen