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image of Topoisomerase II Inhibition in Cancer: A Focus on Metal Complexes

Abstract

DNA topoisomerases, particularly type II, are crucial for DNA processes, such as replication, transcription, and chromosome segregation, making them prime targets for cancer therapy. This review delves into the multifaceted mechanisms of action of type II topoisomerases, highlighting their essential roles beyond cancer progression. It explores recent advancements in screening and designing metallic complexes as inhibitors of topoisomerase II activity. Emphasizing the structural and functional diversity between alpha and beta isoforms, it elucidates their significance in DNA metabolism and genome integrity. Additionally, this review discusses the interplay of topoisomerase II with cellular components, underscoring its regulatory roles in gene expression. Insights into screening and design strategies for metallic complex inhibitors are provided, showcasing their therapeutic potential against cancer. Overall, this review highlights the importance of understanding topoisomerase II inhibition mechanisms and the versatility of metallic complexes in biomedical research, paving the way for novel therapeutic strategies and broader applications beyond cancer therapy.

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2025-06-05
2025-09-15

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References

  1. Nitiss J.L. DNA topoisomerase II and its growing repertoire of biological functions. Nat. Rev. Cancer 2009 9 5 327 337 10.1038/nrc2608 19377505
    [Google Scholar]
  2. Delgado J.L. Hsieh C.M. Chan N.L. Hiasa H. Topoisomerases as anticancer targets. Biochem. J. 2018 475 2 373 398 10.1042/BCJ20160583 29363591
    [Google Scholar]
  3. Chen S.H. Chan N.L. Hsieh T. New mechanistic and functional insights into DNA topoisomerases. Annu. Rev. Biochem. 2013 82 1 139 170 10.1146/annurev‑biochem‑061809‑100002 23495937
    [Google Scholar]
  4. Uusküla-Reimand L. Wilson M.D. Untangling the roles of TOP2A and TOP2B in transcription and cancer. Sci. Adv. 2022 8 44 eadd4920 10.1126/sciadv.add4920 36322662
    [Google Scholar]
  5. Pendleton M. Lindsey R.H. Felix C.A. Grimwade D. Osheroff N. Topoisomerase II and leukemia. Ann. N. Y. Acad. Sci. 2014 1310 1 98 110 10.1111/nyas.12358 24495080
    [Google Scholar]
  6. Pogorelčnik B. Perdih A. Solmajer T. Recent advances in the development of catalytic inhibitors of human DNA topoisomerase IIα as novel anticancer agents. Curr. Med. Chem. 2013 20 5 694 709 10.2174/092986713804999402 23210851
    [Google Scholar]
  7. Gaikwad M. Konkimalla V.B. Salunke-Gawali S. Metal complexes as topoisomerase inhibitors. Inorg. Chim. Acta 2022 542 121089 10.1016/j.ica.2022.121089
    [Google Scholar]
  8. Jiang X. Fielding L.A. Davis H. Carroll W. Lisic E.C. Deweese J.E. Inhibition of topoisomerases by metal thiosemicarbazone complexes. Int. J. Mol. Sci. 2023 24 15 12010 10.3390/ijms241512010 37569386
    [Google Scholar]
  9. Okoro C.O. Fatoki T.H. A mini review of novel topoisomerase II inhibitors as future anticancer agents. Int. J. Mol. Sci. 2023 24 3 2532 10.3390/ijms24032532 36768852
    [Google Scholar]
  10. Vann K.R. Oviatt A.A. Osheroff N. Topoisomerase II poisons: Converting essential enzymes into molecular scissors. Biochemistry 2021 60 21 1630 1641 10.1021/acs.biochem.1c00240 34008964
    [Google Scholar]
  11. Matias-Barrios V.M. Radaeva M. Ho C.H. Lee J. Adomat H. Lallous N. Cherkasov A. Dong X. Optimization of new catalytic topoisomerase II inhibitors as an anti-cancer therapy. Cancers (Basel) 2021 13 15 3675 10.3390/cancers13153675 34359577
    [Google Scholar]
  12. Matias-Barrios V.M. Radaeva M. Song Y. Alperstein Z. Lee A.R. Schmitt V. Lee J. Ban F. Xie N. Qi J. Lallous N. Gleave M.E. Cherkasov A. Dong X. Discovery of new catalytic topoisomerase II inhibitors for anticancer therapeutics. Front. Oncol. 2021 10 633142 10.3389/fonc.2020.633142 33598437
    [Google Scholar]
  13. McKie S.J. Neuman K.C. Maxwell A. DNA topoisomerases: Advances in understanding of cellular roles and multi‐protein complexes via structure‐function analysis. BioEssays 2021 43 4 2000286 10.1002/bies.202000286 33480441
    [Google Scholar]
  14. Schmidt B.H. Osheroff N. Berger J.M. Structure of a topoisomerase II–DNA–nucleotide complex reveals a new control mechanism for ATPase activity. Nat. Struct. Mol. Biol. 2012 19 11 1147 1154 10.1038/nsmb.2388 23022727
    [Google Scholar]
  15. Classen S. Olland S. Berger J.M. Structure of the topoisomerase II ATPase region and its mechanism of inhibition by the chemotherapeutic agent ICRF-187. Proc. Natl. Acad. Sci. USA 2003 100 19 10629 10634 10.1073/pnas.1832879100 12963818
    [Google Scholar]
  16. Williams N.L. Maxwell A. Probing the two-gate mechanism of DNA gyrase using cysteine cross-linking. Biochemistry 1999 38 41 13502 13511 10.1021/bi9912488 10521257
    [Google Scholar]
  17. Roca J. Berger J.M. Harrison S.C. Wang J.C. DNA transport by a type II topoisomerase: Direct evidence for a two-gate mechanism. Proc. Natl. Acad. Sci. USA 1996 93 9 4057 4062 10.1073/pnas.93.9.4057 8633016
    [Google Scholar]
  18. Dutta R. Inouye M. GHKL, an emergent ATPase/kinase superfamily. Trends Biochem. Sci. 2000 25 1 24 28 10.1016/S0968‑0004(99)01503‑0 10637609
    [Google Scholar]
  19. Berger J.M. Gamblin S.J. Harrison S.C. Wang J.C. Structure and mechanism of DNA topoisomerase II. Nature 1996 379 6562 225 232 10.1038/379225a0 8538787
    [Google Scholar]
  20. Cabral J.H.M. Jackson A.P. Smith C.V. Shikotra N. Maxwell A. Liddington R.C. Crystal structure of the breakage–reunion domain of DNA gyrase. Nature 1997 388 6645 903 906 10.1038/42294 9278055
    [Google Scholar]
  21. Bush N.G. Evans-Roberts K. Maxwell A. DNA topoisomerases. Ecosal Plus 2015 6 2 10.1128/ecosalplus.esp‑0010‑2014 26435256
    [Google Scholar]
  22. Bauer D.L.V. Marie R. Rasmussen K.H. Kristensen A. Mir K.U. DNA catenation maintains structure of human metaphase chromosomes. Nucleic Acids Res. 2012 40 22 11428 11434 10.1093/nar/gks931 23066100
    [Google Scholar]
  23. Gonzalez R.E. Lim C.U. Cole K. Bianchini C.H. Schools G.P. Davis B.E. Wada I. Roninson I.B. Broude E.V. Effects of conditional depletion of topoisomerase II on cell cycle progression in mammalian cells. Cell Cycle 2011 10 20 3505 3514 10.4161/cc.10.20.17778 22067657
    [Google Scholar]
  24. Chen T. Sun Y. Ji P. Kopetz S. Zhang W. Topoisomerase IIα in chromosome instability and personalized cancer therapy. Oncogene 2015 34 31 4019 4031 10.1038/onc.2014.332 25328138
    [Google Scholar]
  25. Singh B.N. Achary V.M.M. Panditi V. Sopory S.K. Reddy M.K. Dynamics of tobacco DNA topoisomerases II in cell cycle regulation: To manage topological constrains during replication, transcription and mitotic chromosome condensation and segregation. Plant Mol. Biol. 2017 94 6 595 607 10.1007/s11103‑017‑0626‑4 28634865
    [Google Scholar]
  26. Lee J.H. Berger J.M. Cell cycle-dependent control and roles of DNA topoisomerase II. Genes (Basel) 2019 10 11 859 10.3390/genes10110859 31671531
    [Google Scholar]
  27. Zaim M. Isik S. DNA topoisomerase IIβ stimulates neurite outgrowth in neural differentiated human mesenchymal stem cells through regulation of Rho-GTPases (RhoA/Rock2 pathway) and Nurr1 expression. Stem Cell Res. Ther. 2018 9 1 114 10.1186/s13287‑018‑0859‑4 29695291
    [Google Scholar]
  28. Isik S. Zaim M. Yildiz M.T. Negis Y. Kunduraci T. Karakas N. Arikan G. Cetin G. DNA topoisomerase IIβ as a molecular switch in neural differentiation of mesenchymal stem cells. Ann. Hematol. 2015 94 2 307 318 10.1007/s00277‑014‑2209‑7 25217229
    [Google Scholar]
  29. Bedez C. Lotz C. Batisse C. Broeck A.V. Stote R.H. Howard E. Pradeau-Aubreton K. Ruff M. Lamour V. Post-translational modifications in DNA topoisomerase 2α highlight the role of a eukaryote-specific residue in the ATPase domain. Sci. Rep. 2018 8 1 9272 10.1038/s41598‑018‑27606‑8 29915179
    [Google Scholar]
  30. Ashour M.E. Atteya R. El-Khamisy S.F. Topoisomerase-mediated chromosomal break repair: An emerging player in many games. Nat. Rev. Cancer 2015 15 3 137 151 10.1038/nrc3892 25693836
    [Google Scholar]
  31. Schmidt B.H. Burgin A.B. Deweese J.E. Osheroff N. Berger J.M. A novel and unified two-metal mechanism for DNA cleavage by type II and IA topoisomerases. Nature 2010 465 7298 641 644 10.1038/nature08974 20485342
    [Google Scholar]
  32. Wendorff T.J. Schmidt B.H. Heslop P. Austin C.A. Berger J.M. The structure of DNA-bound human topoisomerase II alpha: Conformational mechanisms for coordinating inter-subunit interactions with DNA cleavage. J. Mol. Biol. 2012 424 3-4 109 124 10.1016/j.jmb.2012.07.014 22841979
    [Google Scholar]
  33. Pommier Y. Leo E. Zhang H. Marchand C. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem. Biol. 2010 17 5 421 433 10.1016/j.chembiol.2010.04.012 20534341
    [Google Scholar]
  34. Fortune J.M. Osheroff N. Topoisomerase II as a target for anticancer drugs: When enzymes stop being nice. Prog. Nucleic Acid Res. Mol. Biol. 2000 64 221 253 10.1016/S0079‑6603(00)64006‑0 10697411
    [Google Scholar]
  35. Gómez-Herreros F. Romero-Granados R. Zeng Z. Álvarez-Quilón A. Quintero C. Ju L. Umans L. Vermeire L. Huylebroeck D. Caldecott K.W. Cortés-Ledesma F. TDP2-dependent non-homologous end-joining protects against topoisomerase II-induced DNA breaks and genome instability in cells and in vivo. PLoS Genet. 2013 9 3 e1003226 10.1371/journal.pgen.1003226 23505375
    [Google Scholar]
  36. Stinson B.M. Loparo J.J. Repair of DNA double-strand breaks by the nonhomologous end joining pathway. Annu. Rev. Biochem. 2021 90 1 137 164 10.1146/annurev‑biochem‑080320‑110356 33556282
    [Google Scholar]
  37. Schellenberg M.J. Appel C.D. Adhikari S. Robertson P.D. Ramsden D.A. Williams R.S. Mechanism of repair of 5′-topoisomerase II–DNA adducts by mammalian tyrosyl-DNA phosphodiesterase 2. Nat. Struct. Mol. Biol. 2012 19 12 1363 1371 10.1038/nsmb.2418 23104055
    [Google Scholar]
  38. Ong K.H. Lai H.Y. Sun D.P. Chen T.J. Huang S.K.H. Tian Y.F. Chou C.L. Shiue Y.L. Chan T.C. Li C.F. Kuo Y.H. Prognostic significance of DNA topoisomerase II Alpha (TOP2A) in cholangiocarcinoma. Front. Biosci. 2023 28 4 75 10.31083/j.fbl2804075 37114547
    [Google Scholar]
  39. Yakkala P.A. Penumallu N.R. Shafi S. Kamal A. Prospects of topoisomerase inhibitors as promising anti-cancer agents. Pharmaceuticals (Basel) 2023 16 10 1456 10.3390/ph16101456 37895927
    [Google Scholar]
  40. Dolanbay S.N. Yilmaz Z.K. Kaya B. Aslim B. Ülküseven B. In vitro biological and in silico screening of novel iron(iii) complexes for DNA-targeted antitumor drug component. New J. Chem. 2023 47 30 14225 14241 10.1039/D3NJ00016H
    [Google Scholar]
  41. Rao V.A. Klein S.R. Agama K.K. Toyoda E. Adachi N. Pommier Y. Shacter E.B. The iron chelator Dp44mT causes DNA damage and selective inhibition of topoisomerase IIalpha in breast cancer cells. Cancer Res. 2009 69 3 948 957 10.1158/0008‑5472.CAN‑08‑1437 19176392
    [Google Scholar]
  42. Brabec V. Kasparkova J. Ruthenium coordination compounds of biological and biomedical significance. DNA binding agents. Coord. Chem. Rev. 2018 376 75 94 10.1016/j.ccr.2018.07.012
    [Google Scholar]
  43. 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 11 9512 10.3390/ijms24119512 37298471
    [Google Scholar]
  44. Tang H. Guo X. Yu W. Gao J. Zhu X. Huang Z. Ou W. Zhang H. Chen L. Chen J. Ruthenium(II) complexes as mitochondrial inhibitors of topoisomerase induced A549 cell apoptosis. J. Inorg. Biochem. 2023 246 112295 10.1016/j.jinorgbio.2023.112295 37348172
    [Google Scholar]
  45. Lee S.Y. Kim C.Y. Nam T.G. Ruthenium complexes as anticancer agents: A brief history and perspectives. Drug Des. Devel. Ther. 2020 14 5375 5392 10.2147/DDDT.S275007 33299303
    [Google Scholar]
  46. Matveevskaya V.V. Pavlov D.I. Sukhikh T.S. Gushchin A.L. Ivanov A.Y. Tennikova T.B. Sharoyko V.V. Baykov S.V. Benassi E. Potapov A.S. Arene–Ruthenium(II) complexes containing 11 H -Indeno[1,2- b]quinoxalin-11-one derivatives and tryptanthrin-6-oxime: Synthesis, characterization, cytotoxicity, and catalytic transfer hydrogenation of aryl ketones. ACS Omega 2020 5 19 11167 11179 10.1021/acsomega.0c01204 32455240
    [Google Scholar]
  47. Zeng L. Gupta P. Chen Y. Wang E. Ji L. Chao H. Chen Z.S. The development of anticancer ruthenium(ii) complexes: From single molecule compounds to nanomaterials. Chem. Soc. Rev. 2017 46 19 5771 5804 10.1039/C7CS00195A 28654103
    [Google Scholar]
  48. Annunziata A. Cucciolito M.E. Di Ronza M. Ferraro G. Hadiji M. Merlino A. Ortiz D. Scopelliti R. Tirani F.F. Dyson P.J. Ruffo F. Ruthenium(II)–arene complexes with glycosylated nhc-carbene co-ligands: Synthesis, hydrolytic behavior, and binding to biological molecules. Organometallics 2023 42 10 952 964 10.1021/acs.organomet.3c00128
    [Google Scholar]
  49. Adhikari S. Nath P. Das A. Datta A. Baildya N. Duttaroy A.K. Pathak S. A review on metal complexes and its anti-cancer activities: Recent updates from in vivo studies. Biomed. Pharmacother. 2024 171 116211 10.1016/j.biopha.2024.116211 38290253
    [Google Scholar]
  50. Kanaoujiya R. Meenakshi; Srivastava, S.; Singh, R.; Mustafa, G. Recent advances and application of ruthenium complexes in tumor malignancy. Mater. Today Proc. 2023 72 2822 2827 10.1016/j.matpr.2022.07.098
    [Google Scholar]
  51. 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 9 4976 10.3390/ijms23094976 35563367
    [Google Scholar]
  52. Zhang P. Huang H. Future potential of osmium complexes as anticancer drug candidates, photosensitizers and organelle-targeted probes. Dalton Trans. 2018 47 42 14841 14854 10.1039/C8DT03432J 30325378
    [Google Scholar]
  53. Huang C. Huang W. Ji P. Song F. Liu T. Li M. Guo H. Huang Y. Yu C. Wang C. Ni W. A pyrazolate osmium (VI) nitride exhibits anticancer activity through modulating protein homeostasis in HepG2 Cells. Int. J. Mol. Sci. 2022 23 21 12779 10.3390/ijms232112779 36361570
    [Google Scholar]
  54. Carter A. Racey S. Veuger S. The role of iron in DNA and genomic instability in cancer, a target for iron chelators that can induce ROS. Appl. Sci. (Basel) 2022 12 19 10161 10.3390/app121910161
    [Google Scholar]
  55. Bau J.T. Kang Z. Austin C.A. Kurz E.U. Salicylate, a catalytic inhibitor of topoisomerase II, inhibits DNA cleavage and is selective for the α isoform. Mol. Pharmacol. 2014 85 2 198 207 10.1124/mol.113.088963 24220011
    [Google Scholar]
  56. Van der Horn J. Souvignier B. Lutz M. Crystallization, structure determination and reticular twinning in iron(III) salicylate: Fe. Crystals (Basel) 2017 7 12 377 [(HSal)(Sal)(H2O)2 10.3390/cryst7120377
    [Google Scholar]
  57. Rao V.A. Iron chelators with topoisomerase-inhibitory activity and their anticancer applications. Antioxid. Redox Signal. 2013 18 8 930 955 10.1089/ars.2012.4877 22900902
    [Google Scholar]
  58. Vejpongsa P. Yeh E.T.H. Topoisomerase 2β: A promising molecular target for primary prevention of anthracycline-induced cardiotoxicity. Clin. Pharmacol. Ther. 2013 95 1 45 52 10.1038/clpt.2013.201 24091715
    [Google Scholar]
  59. Xu X. Persson H.L. Richardson D.R. Molecular pharmacology of the interaction of anthracyclines with iron. Mol. Pharmacol. 2005 68 2 261 271 10.1124/mol.105.013383 15883202
    [Google Scholar]
  60. Mordente A. Meucci E. Martorana G.E. Tavian D. Silvestrini A. Topoisomerases and anthracyclines: Recent advances and perspectives in anticancer therapy and prevention of cardiotoxicity. Curr. Med. Chem. 2017 24 15 1607 1626 27978799
    [Google Scholar]
  61. Zeglis B.M. Divilov V. Lewis J.S. Role of metalation in the topoisomerase IIα inhibition and antiproliferation activity of a series of α-heterocyclic-N4-substituted thiosemicarbazones and their Cu(II) complexes. J. Med. Chem. 2011 54 7 2391 2398 10.1021/jm101532u 21391686
    [Google Scholar]
  62. Shi R. Hou W. Wang Z.Q. Xu X. Biogenesis of iron–sulfur clusters and their role in DNA metabolism. Front. Cell Dev. Biol. 2021 9 735678 10.3389/fcell.2021.735678 34660592
    [Google Scholar]
  63. Vančo J. Šindelář Z. Dvořák Z. Trávníček Z. Iron-salophen complexes involving azole-derived ligands: A new group of compounds with high-level and broad-spectrum in vitro antitumor activity. J. Inorg. Biochem. 2015 142 92 100 10.1016/j.jinorgbio.2014.10.002 25450023
    [Google Scholar]
  64. Gaur K. Pérez Otero S.C. Benjamín-Rivera J.A. Rodríguez I. Loza-Rosas S.A. Vázquez Salgado A.M. Akam E.A. Hernández-Matias L. Sharma R.K. Alicea N. Kowaleff M. Washington A.V. Astashkin A.V. Tomat E. Tinoco A.D. Iron chelator transmetalative approach to inhibit human ribonucleotide reductase. JACS Au 2021 1 6 865 878 10.1021/jacsau.1c00078 34240081
    [Google Scholar]
  65. Lin M.H.C. Chang L.C. Chung C.Y. Huang W.C. Lee M.H. Chen K.T. Lai P.S. Yang J.T. Photochemical internalization of etoposide using dendrimer nanospheres loaded with etoposide and protoporphyrin IX on a glioblastoma cell line. Pharmaceutics 2021 13 11 1877 10.3390/pharmaceutics13111877 34834292
    [Google Scholar]
  66. Chikate R.C. Padhye S.B. Transition metal quinone–thiosemicarbazone complexes 2: Magnetism, ESR and redox behavior of iron (II), iron (III), cobalt (II) and copper (II) complexes of 2-thiosemicarbazido-1,4-naphthoquinone. Polyhedron 2005 24 13 1689 1700 10.1016/j.poly.2005.04.037
    [Google Scholar]
  67. Lee W-C.C. Zhang X.P. Iron(iii) porphyrin complexes as metalloradical catalysts. Nat. Chem. 2023 15 11 1499 1500 10.1038/s41557‑023‑01318‑7 37710050
    [Google Scholar]
  68. Salimi Z. Afsharinasab M. Rostami M. Milasi Y.E. Ezmareh S.F.M. Sakhaei F. Mohammad-Sadeghipour M. Manesh S.M.R. Asemi Z. Iron chelators: As therapeutic agents in diseases. Ann. Med. Surg. (Lond.) 2024 86 5 2759 2776 10.1097/MS9.0000000000001717 38694398
    [Google Scholar]
  69. Yeo J.H. Begam N. Leow W.T. Goh J.X. Zhong Y. Cai Y. Kwa A.L.H. Ironing out persisters? revisiting the iron chelation strategy to target planktonic bacterial persisters harboured in carbapenem-resistant Escherichia coli. Microorganisms 2024 12 5 972 10.3390/microorganisms12050972 38792801
    [Google Scholar]
  70. Lori M.S. Khandani A.K. Dehghannoudeh G. Ohadi M. Ansari M. Therapeutic potential of iron chelators in viral diseases: A systematic review. Curr. Med. Chem. 2024 31 27 4383 4391 10.2174/0109298673259596231211113211 38321902
    [Google Scholar]
  71. Liao G. Chen X. Wu J. Qian C. Wang Y. Ji L. Chao H. Ruthenium(ii) polypyridyl complexes as dual inhibitors of telomerase and topoisomerase. Dalton Trans. 2015 44 34 15145 15156 10.1039/C4DT03585B 25604798
    [Google Scholar]
  72. Elsayed S.A. Harrypersad S. Sahyon H.A. El-Magd M.A. Walsby C.J. Ruthenium (II)/(III) DMSO-based complexes of 2-aminophenyl benzimidazole with in vitro and in vivo anticancer activity. Molecules 2020 25 18 4284 10.3390/molecules25184284 32962014
    [Google Scholar]
  73. Sonkar C. Sarkar S. Mukhopadhyay S. Ruthenium (II)–arene complexes as anti-metastatic agents, and related techniques. RSC Med. Chem. 2022 13 1 22 38
    [Google Scholar]
  74. Noureldeen A.F.H. Aziz S.W. Shouman S.A. Mohamed M.M. Attia Y.M. Ramadan R.M. Elhady M.M. Molecular design, spectroscopic, DFT, pharmacological, and molecular docking studies of novel ruthenium (III)–Schiff base complex: An inhibitor of progression in HepG2 cells. Int. J. Environ. Res. Public Health 2022 19 20 13624 10.3390/ijerph192013624 36294202
    [Google Scholar]
  75. Begić S. Novel complexes of ruthenium (III) with schiff bases and indazole–synthesis and characterization. Biosystems 2019 12 1 294 299
    [Google Scholar]
  76. Savic M. Arsenijevic A. Milovanovic J. Stojanovic B. Stankovic V. Rilak Simovic A. Lazic D. Arsenijevic N. Milovanovic M. Antitumor activity of ruthenium (II) terpyridine complexes towards colon cancer cells in vitro and in vivo. Molecules 2020 25 20 4699 10.3390/molecules25204699 33066568
    [Google Scholar]
  77. 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 10.1021/acs.chemrev.8b00271 30640441
    [Google Scholar]
  78. Gao F. Chao H. Wang J.Q. Yuan Y.X. Sun B. Wei Y.F. Peng B. Ji L.N. Targeting topoisomerase II with the chiral DNA-intercalating ruthenium(II) polypyridyl complexes. J. Biol. Inorg. Chem. 2007 12 7 1015 1027 10.1007/s00775‑007‑0272‑4 17659367
    [Google Scholar]
  79. Gopal Y.N.V. Jayaraju D. Kondapi A.K. Inhibition of topoisomerase II catalytic activity by two ruthenium compounds: A ligand-dependent mode of action. Biochemistry 1999 38 14 4382 4388 10.1021/bi981990s 10194357
    [Google Scholar]
  80. Lin K. Zhao Z.Z. Bo H.B. Hao X.J. Wang J.Q. Applications of ruthenium complex in tumor diagnosis and therapy. Front. Pharmacol. 2018 9 1323 10.3389/fphar.2018.01323 30510511
    [Google Scholar]
  81. Kaur M. Loveleen; Kumar, R. Inhibition of histone deacetylases, topoisomerases and epidermal growth factor receptor by metal-based anticancer agents: Design & synthetic strategies and their medicinal attributes. Bioorg. Chem. 2020 105 104396 10.1016/j.bioorg.2020.104396 33130345
    [Google Scholar]
  82. Kaushal R. Kaur M. Sheetal; Sharma, J.; Nehra, K. Antibacterial and ct-DNA binding studies of new synthesized ruthenium (III) hydroxamate complexes: Design, synthesis, DFT calculations and in vitro study. J. Mol. Struct. 2024 1295 136788 10.1016/j.molstruc.2023.136788
    [Google Scholar]
  83. 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 10.1016/j.ccr.2021.213849
    [Google Scholar]
  84. Santos N.E. Braga S.S. Redesigning nature: Ruthenium flavonoid complexes with antitumour, antimicrobial and cardioprotective activities. Molecules 2021 26 15 4544 10.3390/molecules26154544 34361697
    [Google Scholar]
  85. Du K. Liang J. Wang Y. Kou J. Qian C. Ji L. Chao H. Dual inhibition of topoisomerases I and IIα by ruthenium(ii) complexes containing asymmetric tridentate ligands. Dalton Trans. 2014 43 46 17303 17316 10.1039/C4DT02142H 25315107
    [Google Scholar]
  86. Konkankit C.C. Marker S.C. Knopf K.M. Wilson J.J. Anticancer activity of complexes of the third row transition metals, rhenium, osmium, and iridium. Dalton Trans. 2018 47 30 9934 9974 10.1039/C8DT01858H 29904760
    [Google Scholar]
  87. Bruijnincx P.C.A. Sadler P.J. Controlling platinum, ruthenium, and osmium reactivity for anticancer drug design. Adv. Inorg. Chem. 2009 61 1 62 10.1016/S0898‑8838(09)00201‑3 21258628
    [Google Scholar]
  88. Mani A. Feng T. Gandioso A. Vinck R. Notaro A. Gourdon L. Burckel P. Saubaméa B. Blacque O. Cariou K. Belgaied J.E. Chao H. Gasser G. Structurally simple osmium (II) polypyridyl complexes as photosensitizers for photodynamic therapy in the near infrared. Angew. Chem. Int. Ed. 2023 62 20 e202218347 10.1002/anie.202218347 36917074
    [Google Scholar]
  89. Nielson A.J. Griffith W.P. Complexes of osmium(VI) with catechol and substituted catechols. J. Chem. Soc., Dalton Trans. 1978 11 1501 1506 10.1039/dt9780001501
    [Google Scholar]
  90. Szczepaniak A. Fichna J. Organometallic compounds and metal complexes in current and future treatments of inflammatory bowel disease and colorectal cancer—A critical review. Biomolecules 2019 9 9 398 10.3390/biom9090398 31443436
    [Google Scholar]
  91. Cerón-Camacho R. Roque-Ramires M.A. Ryabov A.D. Le Lagadec R. Cyclometalated osmium compounds and beyond: Synthesis, properties, applications. Molecules 2021 26 6 1563 10.3390/molecules26061563 33809231
    [Google Scholar]
  92. Xiang J. Su Q.Q. Luo L.J. Lau T.C. Synthesis and reactivity of an osmium(iii) aminoguanidine complex. Dalton Trans. 2019 48 30 11404 11410 10.1039/C9DT01711A 31282913
    [Google Scholar]
  93. Hildebrandt J. Häfner N. Görls H. Barth M.C. Dürst M. Runnebaum I.B. Weigand W. Novel nickel (II), palladium (II), and platinum (II) complexes with O, S bidendate cinnamic acid ester derivatives: An in vitro cytotoxic comparison to ruthenium (II) and osmium (II) analogues. Int. J. Mol. Sci. 2022 23 12 6669 10.3390/ijms23126669 35743112
    [Google Scholar]
  94. Czarnomysy R. Radomska D. Szewczyk O.K. Roszczenko P. Bielawski K. Platinum and palladium complexes as promising sources for antitumor treatments. Int. J. Mol. Sci. 2021 22 15 8271 10.3390/ijms22158271 34361037
    [Google Scholar]
  95. Göktürk T. Topkaya C. Sakallı Çetin E. Güp R. New trinuclear nickel(II) complexes as potential topoisomerase I/IIα inhibitors: In vitro DNA binding, cleavage and cytotoxicity against human cancer cell lines. Chem. Zvesti 2022 76 4 2093 2109 10.1007/s11696‑021‑02005‑y
    [Google Scholar]
  96. Alqasaimeh M.M. Abu-Yamin A-A.M. Matar S.A. Sarairah I.A. Salman M.M. Al-As’ad R.M. Synthesis and characterization of a new Schiff-base derivative as an optical nickel (II) chemosensor and its antimicrobial activity. J. Photochem. Photobiol. Chem. 2024 447 115277 10.1016/j.jphotochem.2023.115277
    [Google Scholar]
  97. Yu H. Zhang W. Yu Q. Huang F.P. Bian H.D. Liang H. Ni (II) complexes with Schiff base ligands: Preparation, characterization, DNA/protein interaction and cytotoxicity studies. Molecules 2017 22 10 1772 10.3390/molecules22101772 29064419
    [Google Scholar]
  98. Akinyemi A.O. Pereira G.B.S. Oliveira G.P. Lima M.A. Rocha J.S. Costa V.A. Fortaleza D.B. Teixeira T. Zanotti K. Forim M.R. Araujo-Neto J.H. Ellena J. Rocha F.V. Palladium (II) complexes as inhibitors of cathepsin B and topoisomerase I beta: Synthesis, characterization, and cytotoxicity. J. Mol. Struct. 2023 1294 136460 10.1016/j.molstruc.2023.136460
    [Google Scholar]
  99. Rocha F.V. Barra C.V. Garrido S.S. Manente F.A. Carlos I.Z. Ellena J. Fuentes A.S.C. Gautier A. Morel L. Mauro A.E. Netto A.V.G. Cationic Pd(II) complexes acting as topoisomerase II inhibitors: Synthesis, characterization, DNA interaction and cytotoxicity. J. Inorg. Biochem. 2016 159 165 168 10.1016/j.jinorgbio.2016.02.039 27045995
    [Google Scholar]
  100. Fong T.T.H. Lok C.N. Chung C.Y.S. Fung Y.M.E. Chow P.K. Wan P.K. Che C.M. Cyclometalated palladium(II) n‐heterocyclic carbene complexes: Anticancer agents for potent in vitro cytotoxicity and in vivo tumor growth suppression. Angew. Chem. Int. Ed. 2016 55 39 11935 11939 10.1002/anie.201602814 27571430
    [Google Scholar]
  101. Dasari S. Tchounwou P.B. Cisplatin in cancer therapy: Molecular mechanisms of action. Eur. J. Pharmacol. 2014 740 364 378 10.1016/j.ejphar.2014.07.025 25058905
    [Google Scholar]
  102. Buyana B. Naki T. Alven S. Aderibigbe B.A. Nanoparticles loaded with platinum drugs for colorectal cancer therapy. Int. J. Mol. Sci. 2022 23 19 11261 10.3390/ijms231911261 36232561
    [Google Scholar]
  103. Kuchtanin V. Kleščíková L. Šoral M. Fischer R. Růžičková Z. Rakovský E. Moncoľ J. Segľa P. Nickel(II) Schiff base complexes: Synthesis, characterization and catalytic activity in Kumada–Corriu cross-coupling reactions. Polyhedron 2016 117 90 96 10.1016/j.poly.2016.05.037
    [Google Scholar]
  104. Rajasekar M. Sreedaran S. Prabu R. Narayanan V. Jegadeesh R. Raaman N. Kalilur Rahiman A. Synthesis, characterization, and antimicrobial activities of nickel(II) and copper(II) Schiff-base complexes. J. Coord. Chem. 2010 63 1 136 146 10.1080/00958970903296362
    [Google Scholar]
  105. He X. Zeng L. Yang G. Xie L. Sun X. Tan L. DNA binding, photocleavage and topoisomerase inhibitory activity of polypyridyl ruthenium(II) complexes containing the same ancillary ligand and different main ligands. Inorg. Chim. Acta 2013 408 9 17 10.1016/j.ica.2013.08.010
    [Google Scholar]
  106. Zmejkovski B.B. Pantelić N.Đ. Kaluđerović G.N. Palladium(II) complexes: Structure, development and cytotoxicity from cisplatin analogues to chelating ligands with N stereocenters. Inorg. Chim. Acta 2022 534 120797 10.1016/j.ica.2022.120797
    [Google Scholar]
  107. Ramadan A.E.M.M. Macrocyclic nickel(II) complexes: Synthesis, characterization, superoxide scavenging activity and DNA-binding. J. Mol. Struct. 2012 1015 56 66 10.1016/j.molstruc.2012.01.048
    [Google Scholar]
  108. Tsymbal L.V. Andriichuk I.L. Shova S. Trzybiński D. Woźniak K. Arion V.B. Lampeka Y.D. Coordination polymers of the macrocyclic nickel(ii) and copper(ii) complexes with isomeric benzenedicarboxylates: The case of spatial complementarity between the bis-macrocyclic complexes and o -Phthalate. Cryst. Growth Des. 2021 21 4 2355 2370 10.1021/acs.cgd.1c00011
    [Google Scholar]
  109. Sindhu S. Arockiasamy S. Synthesis, crystal structure, thermal stability and biological study of bis(2-methoxy-6-[(E)-(propylimino)methyl]phenolatonickel(II) complex. Heliyon 2024 10 2 e24108 10.1016/j.heliyon.2024.e24108 38293524
    [Google Scholar]
  110. Savir S. Liew J.W.K. Vythilingam I. Lim Y.A.L. Tan C.H. Sim K.S. Lee V.S. Maah M.J. Tan K.W. Nickel (II) complexes with polyhydroxybenzaldehyde and O, N, S tridentate thiosemicarbazone ligands: Synthesis, cytotoxicity, antimalarial activity, and molecular docking studies. J. Mol. Struct. 2021 1242 130815 10.1016/j.molstruc.2021.130815
    [Google Scholar]
  111. Asadi Z. Mandegani Z. Asadi M. Pakiari A.H. Salarhaji M. Manassir M. Karbalaei-Heidari H.R. Rastegari B. Sedaghat M. Substituted effect on some water-soluble Mn(II) salen complexes: DNA binding, cytotoxicity, molecular docking, DFT studies and theoretical IR & UV studies. Spectrochim. Acta A Mol. Biomol. Spectrosc. 2019 206 278 294 10.1016/j.saa.2018.08.020 30121473
    [Google Scholar]
  112. Ma X. Wang H. Chen W. N-heterocyclic carbene-stabilized palladium complexes as organometallic catalysts for bioorthogonal cross-coupling reactions. J. Org. Chem. 2014 79 18 8652 8658 10.1021/jo5014228 25144406
    [Google Scholar]
  113. Dangalov M. Petrov P. Vassilev N.G. N-heterocyclic bis-carbene palladium complexes derived from functionalized naphthalimides – Synthesis, structure elucidation and DFT study. J. Mol. Struct. 2021 1230 129944 10.1016/j.molstruc.2021.129944
    [Google Scholar]
  114. Desai S.P. Mondal M. Choudhury J. Chelating bis-N-heterocyclic carbene–palladium (II) complexes for oxidative arene C–H functionalization. Organometallics 2015 34 12 2731 2736 10.1021/om501163m
    [Google Scholar]
  115. Al-Saif F.A. Al-Humaidi J.Y. Binjawhar D.N. Refat M.S. Six new palladium(II) mixed ligand complexes of 2-, 3-, 4-monosubstituted derivative of pyridine ring with caffeine moiety: Synthesis, spectroscopic, morphological structures, thermal, antimicrobial and anticancer properties. J. Mol. Struct. 2020 1218 128547 10.1016/j.molstruc.2020.128547
    [Google Scholar]
  116. Ferraro V. Genesin L. Castro J. Pietrobon L. Vavasori A. Bortoluzzi M. Organometallic palladium(II) complexes with N-((pyridin-2-yl)methylene)-4-amino-2,1,3-benzothiadiazole: Synthesis, characterization and reactivity. J. Organomet. Chem. 2023 993 122711 10.1016/j.jorganchem.2023.122711
    [Google Scholar]
  117. Fahmy H.M. Mosleh A.M. El-Sayed A.A. El-Sherif A.A. Novel palladium(II) and Zinc(II) Schiff base complexes: Synthesis, biophysical studies, and anticancer activity investigation. J. Trace Elem. Med. Biol. 2023 79 127236 10.1016/j.jtemb.2023.127236 37285632
    [Google Scholar]
  118. Forooghi K. Rudbari H.A. Stagno C. Iraci N. Cuevas-Vicario J.V. Kordestani N. Schirmeister T. Efferth T. Omer E.A. Moini N. Aryaeifar M. Blacque O. Azadbakht R. Micale N. Structural features and antiproliferative activity of Pd(ii) complexes with halogenated ligands: A comparative study between Schiff base and reduced Schiff base complexes. Dalton Trans. 2024 53 25 10571 10591 10.1039/D4DT00132J 38855858
    [Google Scholar]
  119. Macieja A. Kopa P. Galita G. Pastwa E. Majsterek I. Poplawski T. Comparison of the effect of three different topoisomerase II inhibitors combined with cisplatin in human glioblastoma cells sensitized with double strand break repair inhibitors. Mol. Biol. Rep. 2019 46 4 3625 3636 10.1007/s11033‑019‑04605‑0 31020489
    [Google Scholar]
  120. Tchounwou P.B. Dasari S. Noubissi F.K. Ray P. Kumar S. Advances in our understanding of the molecular mechanisms of action of cisplatin in cancer therapy. J. Exp. Pharmacol. 2021 13 303 328 10.2147/JEP.S267383 33776489
    [Google Scholar]
  121. Zhang Y.J. Li A.J. Han Y. Yin L. Lin M.B. Inhibition of Girdin enhances chemosensitivity of colorectal cancer cells to oxaliplatin. World J. Gastroenterol. 2014 20 25 8229 8236 10.3748/wjg.v20.i25.8229 25009397
    [Google Scholar]
  122. Fang Z. Gong C. Ye Z. Wang W. Zhu M. Hu Y. Liu Z. Zhou W. Li H. TOPBP1 regulates resistance of gastric cancer to oxaliplatin by promoting transcription of PARP1. DNA Repair (Amst.) 2022 111 103278 10.1016/j.dnarep.2022.103278 35124372
    [Google Scholar]
  123. Rossman J. Reddy V. Cantor A. Miley D. Robert F. Phase II study of dose-intense chemotherapy with sequential topoisomerase-targeting regimens with irinotecan/oxaliplatin followed by etoposide/carboplatin in chemotherapy naive patients with extensive small cell lung cancer. Lung Cancer 2011 72 2 219 223 10.1016/j.lungcan.2010.08.023 20934233
    [Google Scholar]
  124. Ferraro M.G. Piccolo M. Misso G. Santamaria R. Irace C. Bioactivity and development of small non-platinum metal-based chemotherapeutics. Pharmaceutics 2022 14 5 954 10.3390/pharmaceutics14050954 35631543
    [Google Scholar]
  125. Lisic E.C. Grossarth S.N. Bowman S.B. Hill J.L. Beck M.W. Deweese J.E. Jiang X. New copper (ii), palladium (ii), and platinum (ii) 2-acetylpyrazine tert-butylthiosemicarbazone complexes: Inhibition of human topoisomerase IIα and activity against breast cancer cells. Open J. Med. Chem. 2022 12 1 1 13 10.4236/ojmc.2022.121001
    [Google Scholar]
  126. Fabijańska M. Kasprzak M.M. Ochocki J. Ruthenium (II) and platinum (II) complexes with biologically active aminoflavone ligands exhibit in vitro anticancer activity. Int. J. Mol. Sci. 2021 22 14 7568 10.3390/ijms22147568 34299199
    [Google Scholar]
  127. Liang X. Wu Q. Luan S. Yin Z. He C. Yin L. Zou Y. Yuan Z. Li L. Song X. He M. Lv C. Zhang W. A comprehensive review of topoisomerase inhibitors as anticancer agents in the past decade. Eur. J. Med. Chem. 2019 171 129 168 10.1016/j.ejmech.2019.03.034 30917303
    [Google Scholar]
  128. Molinaro C. Wambang N. Bousquet T. Vercoutter-Edouart A.S. Pélinski L. Cailliau K. Martoriati A. A novel copper (II) indenoisoquinoline complex inhibits topoisomerase I, induces G2 phase arrest, and autophagy in three adenocarcinomas. Front. Oncol. 2022 12 837373 10.3389/fonc.2022.837373 35280788
    [Google Scholar]
  129. Patra M. Gasser G. The medicinal chemistry of ferrocene and its derivatives. 2017
    [Google Scholar]
  130. Beebe S.J. Celestine M.J. Bullock J.L. Sandhaus S. Arca J.F. Cropek D.M. Ludvig T.A. Foster S.R. Clark J.S. Beckford F.A. Tano C.M. Tonsel-White E.A. Gurung R.K. Stankavich C.E. Tse-Dinh Y.C. Jarrett W.L. Holder A.A. Synthesis, characterization, DNA binding, topoisomerase inhibition, and apoptosis induction studies of a novel cobalt(III) complex with a thiosemicarbazone ligand. J. Inorg. Biochem. 2020 203 110907 10.1016/j.jinorgbio.2019.110907 31715377
    [Google Scholar]
  131. Wambang N. Schifano-Faux N. Aillerie A. Baldeyrou B. Jacquet C. Bal-Mahieu C. Bousquet T. Pellegrini S. Ndifon P.T. Meignan S. Goossens J.F. Lansiaux A. Pélinski L. Synthesis and biological activity of ferrocenyl indeno[1,2-c]isoquinolines as topoisomerase II inhibitors. Bioorg. Med. Chem. 2016 24 4 651 660 10.1016/j.bmc.2015.12.033 26740155
    [Google Scholar]
  132. Chrabąszcz K. Błauż A. Gruchała M. Wachulec M. Rychlik B. Plażuk D. Synthesis and biological activity of ferrocenyl and ruthenocenyl analogues of etoposide: discovery of a novel dual inhibitor of topoisomerase II activity and tubulin polymerization. Chemistry 2021 27 20 6254 6262 10.1002/chem.202005133 33465263
    [Google Scholar]
  133. Yan Y.K. Melchart M. Habtemariam A. Sadler P.J. Organometallic chemistry, biology and medicine: Ruthenium arene anticancer complexes. Chem. Commun. (Camb.) 2005 38 4764 4776 10.1039/b508531b 16193110
    [Google Scholar]
  134. Wilson J.T. Jiang X. McGill B.C. Lisic E.C. Deweese J.E. Examination of the impact of copper(II) α-(N)-heterocyclic thiosemicarbazone complexes on DNA Topoisomerase IIα. Chem. Res. Toxicol. 2016 29 4 649 658 10.1021/acs.chemrestox.5b00471 26982206
    [Google Scholar]
  135. Wilson C.R. Fagenson A.M. Ruangpradit W. Muller M.T. Munro O.Q. Gold(III) complexes of pyridyl- and isoquinolylamido ligands: structural, spectroscopic, and biological studies of a new class of dual topoisomerase I and II inhibitors. Inorg. Chem. 2013 52 14 7889 7906 10.1021/ic400339z 23815163
    [Google Scholar]
  136. Lisic E.C. Cu (II) propionyl-thiazole thiosemicarbazone complexes: Crystal structure, inhibition of human topoisomerase IIα, and activity against breast cancer cells. Open J. Med. Chem. 2018 8 2 30 46 10.4236/ojmc.2018.82004
    [Google Scholar]
  137. Khan R.A. Arjmand F. Tabassum S. Monari M. Marchetti F. Pettinari C. Organometallic ruthenium(II) scorpionate as topo IIα inhibitor; in vitro binding studies with DNA, HPLC analysis and its anticancer activity. J. Organomet. Chem. 2014 771 47 58 10.1016/j.jorganchem.2014.05.013
    [Google Scholar]
  138. de Souza Í.P. de Melo A.C.C. Rodrigues B.L. Bortoluzzi A. Poole S. Molphy Z. McKee V. Kellett A. Fazzi R.B. da Costa Ferreira A.M. Pereira-Maia E.C. Antitumor copper(II) complexes with hydroxyanthraquinones and N,N-heterocyclic ligands. J. Inorg. Biochem. 2023 241 112121 10.1016/j.jinorgbio.2023.112121 36696836
    [Google Scholar]
  139. Shinde Y. Patil R. Konkimalla V.B. Merugu S.B. Mokashi V. Harihar S. Marrot J. Butcher R.J. Salunke-Gawali S. Keto-enol tautomerism of hydroxynaphthoquinoneoxime ligands: Copper complexes and topoisomerase inhibition activity. J. Mol. Struct. 2022 1262 133081 10.1016/j.molstruc.2022.133081
    [Google Scholar]
  140. Behera P.K. Maity L. Roy S. Das A. Sahu P. Kisan H.K. Changotra A. Isab A.A. Fettouhi M.B. Bairagi A. Chatterjee N. Dinda J. Therapeutic potential of Ag(i)–, Au(i)–, and Au(iii)–NHC complexes of 3-pyridyl wingtip N-heterocyclic carbenes (NHCs) against lung cancer. New J. Chem. 2023 47 40 18835 18848 10.1039/D3NJ02882H
    [Google Scholar]
  141. Sâmia L.B.P. Parrilha G.L. Da Silva J.G. Ramos J.P. Souza-Fagundes E.M. Castelli S. Vutey V. Desideri A. Beraldo H. Metal complexes of 3-(4-bromophenyl)-1-pyridin-2-ylprop-2-en-1-one thiosemicarbazone: Cytotoxic activity and investigation on the mode of action of the gold(III) complex. Biometals 2016 29 3 515 526 10.1007/s10534‑016‑9933‑5 27091443
    [Google Scholar]
  142. Legina M.S. Nogueira J.J. Kandioller W. Jakupec M.A. González L. Keppler B.K. Biological evaluation of novel thiomaltol-based organometallic complexes as topoisomerase IIα inhibitors. J. Biol. Inorg. Chem. 2020 25 3 451 465 10.1007/s00775‑020‑01775‑2 32193613
    [Google Scholar]
  143. Hearn J.M. Hughes G.M. Romero-Canelón I. Munro A.F. Rubio-Ruiz B. Liu Z. Carragher N.O. Sadler P.J. Pharmaco-genomic investigations of organo-iridium anticancer complexes reveal novel mechanism of action. Metallomics 2018 10 1 93 107 10.1039/C7MT00242D 29131211
    [Google Scholar]
  144. Albert J. Janabi B.A. Granell J. Hashemi M.S. Sainz D. Khosa M.K. Calvis C. Messeguer R. Baldomà L. Badia J. Font-Bardia M. Synthesis and biological properties of palladium(II) cyclometallated compounds derived from (E)-2-((4-hydroxybenzylidene)amino)phenol. J. Organomet. Chem. 2023 983 122555 10.1016/j.jorganchem.2022.122555
    [Google Scholar]
  145. Schmidlehner M. Flocke L.S. Roller A. Hejl M. Jakupec M.A. Kandioller W. Keppler B.K. Cytotoxicity and preliminary mode of action studies of novel 2-aryl-4-thiopyrone-based organometallics. Dalton Trans. 2016 45 2 724 733 10.1039/C5DT02722E 26630201
    [Google Scholar]
  146. Rendošová M. Vargová Z. Sabolová D. Imrichová N. Hudecová D. Gyepes R. Lakatoš B. Elefantová K. Silver pyridine-2-sulfonate complex - its characterization, DNA binding, topoisomerase I inhibition, antimicrobial and anticancer response. J. Inorg. Biochem. 2018 186 206 216 10.1016/j.jinorgbio.2018.06.006 29960924
    [Google Scholar]
  147. Movahedi E. Razmazma H. Rezvani A. Ebrahimi A. Binding profile of a mixed-ligand silver(I) complex with DNA and Topoisomerase I. Comput. Biol. Chem. 2023 103 107831 10.1016/j.compbiolchem.2023.107831 36822076
    [Google Scholar]
  148. Pérez Sergio D.H.C. New acridine thiourea gold(I) anticancer agents: Targeting the nucleus and inhibiting vasculogenic mimicry. ACS Chem. Biol. 2017 12 6 1524 1537 10.1021/acschembio.7b00090 28388047
    [Google Scholar]
  149. Chimento A. Saturnino C. Iacopetta D. Mazzotta R. Caruso A. Plutino M.R. Mariconda A. Ramunno A. Sinicropi M.S. Pezzi V. Longo P. Inhibition of human topoisomerase I and II and anti-proliferative effects on MCF-7 cells by new titanocene complexes. Bioorg. Med. Chem. 2015 23 22 7302 7312 10.1016/j.bmc.2015.10.030 26526741
    [Google Scholar]
  150. Madabhushi R. The roles of DNA topoisomerase IIβ in transcription. Int. J. Mol. Sci. 2018 19 7 1917 10.3390/ijms19071917 29966298
    [Google Scholar]
  151. Allison S.J. Sadiq M. Baronou E. Cooper P.A. Dunnill C. Georgopoulos N.T. Latif A. Shepherd S. Shnyder S.D. Stratford I.J. Wheelhouse R.T. Willans C.E. Phillips R.M. Preclinical anti-cancer activity and multiple mechanisms of action of a cationic silver complex bearing N-heterocyclic carbene ligands. Cancer Lett. 2017 403 98 107 10.1016/j.canlet.2017.04.041 28624622
    [Google Scholar]
  152. Hearn J.M. Romero-Canelón I. Qamar B. Liu Z. Hands-Portman I. Sadler P.J. Organometallic Iridium(III) anticancer complexes with new mechanisms of action: NCI-60 screening, mitochondrial targeting, and apoptosis. ACS Chem. Biol. 2013 8 6 1335 1343 10.1021/cb400070a 23618382
    [Google Scholar]
  153. Sohrabi M. Saeedi M. Larijani B. Mahdavi M. Recent advances in biological activities of rhodium complexes: Their applications in drug discovery research. Eur. J. Med. Chem. 2021 216 113308 10.1016/j.ejmech.2021.113308 33713976
    [Google Scholar]
  154. Scattolin T. A critical review of palladium organometallic anticancer agents. Cell. Rep. Phys. Sci. 2021 2 6 100446 10.1016/j.xcrp.2021.100446
    [Google Scholar]
  155. Yan J.J. Chow A.L.F. Leung C.H. Sun R.W.Y. Ma D.L. Che C.M. Cyclometalated gold(iii) complexes with N-heterocyclic carbene ligands as topoisomerase I poisons. Chem. Commun. (Camb.) 2010 46 22 3893 3895 10.1039/c001216e 20401423
    [Google Scholar]
  156. Silva L.T.P. Pereira G.B.S. Porto de Oliveira G. Lima M.A. Honorato de Araujo-Neto J. Akinyemi A.O. Vieira M.A. Nascimento-Júnior N.M. Lira de Farias R. Ellena J.A. Vieira de Godoy Netto A. Rocha F.V. Synthesis, characterization, cytotoxicity study, interaction with DNA and topoisomerase IIα of square-planar complexes with thiosemicarbazones. Polyhedron 2024 257 117021 10.1016/j.poly.2024.117021
    [Google Scholar]
  157. Rocha F.V. Farias R.L. Lima M.A. Batista V.S. Nascimento-Júnior N.M. Garrido S.S. Leopoldino A.M. Goto R.N. Oliveira A.B. Beck J. Landvogt C. Mauro A.E. Netto A.V.G. Computational studies, design and synthesis of Pd(II)-based complexes: Allosteric inhibitors of the Human Topoisomerase-IIα. J. Inorg. Biochem. 2019 199 110725 10.1016/j.jinorgbio.2019.110725 31374424
    [Google Scholar]
  158. Madabhushi R. Gao F. Pfenning A.R. Pan L. Yamakawa S. Seo J. Rueda R. Phan T.X. Yamakawa H. Pao P.C. Stott R.T. Gjoneska E. Nott A. Cho S. Kellis M. Tsai L.H. Activity-induced DNA breaks govern the expression of neuronal early-response genes. Cell 2015 161 7 1592 1605 10.1016/j.cell.2015.05.032 26052046
    [Google Scholar]
  159. Lucaciu R.L. Hangan A.C. Sevastre B. Oprean L.S. Metallo-drugs in cancer therapy: Past, present and future. Molecules 2022 27 19 6485 10.3390/molecules27196485 36235023
    [Google Scholar]
  160. Che C.M. Siu F.M. Metal complexes in medicine with a focus on enzyme inhibition. Curr. Opin. Chem. Biol. 2010 14 2 255 261 10.1016/j.cbpa.2009.11.015 20018553
    [Google Scholar]
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Topoisomerase II Inhibition in Cancer: A Focus on Metal Complexes
Bentham Science Publishers ; https://doi.org/10.2174/0113895575370547250526062144
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  • Article Type:     Review Article
Keywords: inhibition ; DNA topoisomerases ; alpha and beta isoforms ; cancer therapy ; mechanism of action ; metallic complexes

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