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Current Medicinal Chemistry

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Review Article

Metal-Organic Compounds as Anticancer Agents: Versatile Building Blocks for Selective Action on G-quadruplexes

Author(s): Patricia M. Toro, Marianela Saldias* and Gabriela Valenzuela-Barra

Volume 30, Issue 5, 2023

Published on: 04 August, 2022

Page: [573 - 600] Pages: 28

DOI: 10.2174/0929867329666220606160209

Price: $65

Abstract

Background: Since the 1980s, cancer research has focused primarily on developing new therapeutic agents targeting DNA alterations rather than understanding cancer as an integrated system composed of several modules. In this sense, G-quadruplex (G4) nucleic acids are a promising target for drug development for cancer therapy since they exist in the chromosomal telomeric sequences and the promoter regions of numerous genes. The G4 structures within telomeric DNA can inhibit telomerase activity and prevent the proliferation and immortalization of cancer cells. Furthermore, such G4 systems within the promoter regions of oncogenes can inhibit the transcription and expression of the oncogene.

Objective: The rational design of small molecules such as organic ligands and their metal- organic derivative compounds can stabilize G4 structures through different binding modes on several G4 DNA topologies. Metal-based compounds have demonstrated their competitiveness compared to organic molecules to distinguish G4 over the DNA duplex owing to their convenient coordination features, positive charge, and electron density promoted by organic ligand.

Results: This article is a comprehensive review of metal compounds G4-binders and their structural features that confer them the ability to recognize G-quartets and stabilize several DNA G4s.

Conclusion: This stabilization can be achieved through extended square aromatic surfaces, increased hydrophobicity, different auxiliary ligands, axially coordinated ligands, and the nature of the metal center.

Keywords: Cancer therapy, G-quadruplex , telomerase, oncogene promoters, G4-ligands, metallo-compounds.

« Previous Next »
[1]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[2]
Riss, J.; Khanna, C.; Koo, S.; Chandramouli, G.V.R.; Yang, H.H.; Hu, Y.; Kleiner, D.E.; Rosenwald, A.; Schaefer, C.F.; Ben-Sasson, S.A.; Yang, L.; Powell, J.; Kane, D.W.; Star, R.A.; Aprelikova, O.; Bauer, K.; Vasselli, J.R.; Maranchie, J.K.; Kohn, K.W.; Buetow, K.H.; Linehan, W.M.; Weinstein, J.N.; Lee, M.P.; Klausner, R.D.; Barrett, J.C. Cancers as wounds that do not heal: differences and similarities between renal regeneration/repair and renal cell carcinoma. Cancer Res., 2006, 66(14), 7216-7224.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-0040] [PMID: 16849569]
[3]
Roxo, C.; Kotkowiak, W.; Pasternak, A. G-Quadruplex-forming aptamers-characteristics, applications, and perspectives. Molecules, 2019, 24(20), 3781.
[http://dx.doi.org/10.3390/molecules24203781] [PMID: 31640176]
[4]
Bidzinska, J.; Cimino-Reale, G.; Zaffaroni, N.; Folini, M. G-quadruplex structures in the human genome as novel therapeutic targets. Molecules, 2013, 18(10), 12368-12395.
[http://dx.doi.org/10.3390/molecules181012368] [PMID: 24108400]
[5]
Huppert, J.L.; Balasubramanian, S. Prevalence of quadruplexes in the human genome. Nucleic Acids Res., 2005, 33(9), 2908-2916.
[http://dx.doi.org/10.1093/nar/gki609] [PMID: 15914667]
[6]
Chambers, V.S.; Marsico, G.; Boutell, J.M.; Di Antonio, M.; Smith, G.P.; Balasubramanian, S. High-throughput sequencing of DNA G-quadruplex structures in the human genome. Nat. Biotechnol., 2015, 33(8), 877-881.
[http://dx.doi.org/10.1038/nbt.3295] [PMID: 26192317]
[7]
Collie, G.W.; Parkinson, G.N. The application of DNA and RNA G-quadruplexes to therapeutic medicines. Chem. Soc. Rev., 2011, 40(12), 5867-5892.
[http://dx.doi.org/10.1039/c1cs15067g] [PMID: 21789296]
[8]
Taylor, J.P. Neurodegenerative diseases: G-quadruplex poses quadruple threat. Nature, 2014, 507(7491), 175-177.
[http://dx.doi.org/10.1038/nature13067] [PMID: 24598546]
[9]
Xi, H.; Juhas, M.; Zhang, Y. G-quadruplex based biosensor: A potential tool for SARS-CoV-2 detection. Biosens. Bioelectron., 2020, 167, 112494.
[http://dx.doi.org/10.1016/j.bios.2020.112494] [PMID: 32791468]
[10]
Tian, T.; Xiao, H.; Zhou, X. A review: G-Quadruplex’s applications in biological target detection and drug delivery. Curr. Top. Med. Chem., 2015, 15(19), 1988-2001.
[http://dx.doi.org/10.2174/1568026615666150515151142] [PMID: 25980411]
[11]
de Lange, T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev., 2005, 19(18), 2100-2110.
[http://dx.doi.org/10.1101/gad.1346005] [PMID: 16166375]
[12]
Asamitsu, S.; Obata, S.; Yu, Z.; Bando, T.; Sugiyama, H. Recent progress of targeted G-Quadruplex-preferred ligands toward cancer therapy. Molecules, 2019, 24(3), 429.
[http://dx.doi.org/10.3390/molecules24030429] [PMID: 30682877]
[13]
Jafri, M.A.; Ansari, S.A.; Alqahtani, M.H.; Shay, J.W. Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies. Genome Med., 2016, 8(1), 69.
[http://dx.doi.org/10.1186/s13073-016-0324-x] [PMID: 27323951]
[14]
Palumbo, S.L.; Ebbinghaus, S.W.; Hurley, L.H. Formation of a unique end-to-end stacked pair of G-quadruplexes in the hTERT core promoter with implications for inhibition of telomerase by G-quadruplex-interactive ligands. J. Am. Chem. Soc., 2009, 131(31), 10878-10891.
[http://dx.doi.org/10.1021/ja902281d] [PMID: 19601575]
[15]
Dang, C.V. MYC on the path to cancer. Cell, 2012, 149(1), 22-35.
[http://dx.doi.org/10.1016/j.cell.2012.03.003] [PMID: 22464321]
[16]
Adams, J.M.; Cory, S. The Bcl-2 protein family: arbiters of cell survival. Science, 1998, 281(5381), 1322-1326.
[http://dx.doi.org/10.1126/science.281.5381.1322] [PMID: 9735050]
[17]
Radha, G.; Raghavan, S.C. BCL2: A promising cancer therapeutic target. Biochim. Biophys. Acta Rev. Cancer, 2017, 1868(1), 309-314.
[http://dx.doi.org/10.1016/j.bbcan.2017.06.004] [PMID: 28647470]
[18]
Shaw, T.J.; Keszthelyi, E.J.; Tonary, A.M.; Cada, M.; Vanderhyden, B.C. Cyclic AMP in ovarian cancer cells both inhibits proliferation and increases c-KIT expression. Exp. Cell Res., 2002, 273(1), 95-106.
[http://dx.doi.org/10.1006/excr.2001.5426] [PMID: 11795950]
[19]
Edling, C.E.; Hallberg, B. c-Kit--a hematopoietic cell essential receptor tyrosine kinase. Int. J. Biochem. Cell Biol., 2007, 39(11), 1995-1998.
[http://dx.doi.org/10.1016/j.biocel.2006.12.005] [PMID: 17350321]
[20]
Blume-Jensen, P.; Hunter, T. Oncogenic kinase signalling. Nature, 2001, 411(6835), 355-365.
[http://dx.doi.org/10.1038/35077225] [PMID: 11357143]
[21]
Rankin, S.; Reszka, A.P.; Huppert, J.; Zloh, M.; Parkinson, G.N.; Todd, A.K.; Ladame, S.; Balasubramanian, S.; Neidle, S.; Putative, D.N.A. Putative DNA quadruplex formation within the human c-kit oncogene. J. Am. Chem. Soc., 2005, 127(30), 10584-10589.
[http://dx.doi.org/10.1021/ja050823u] [PMID: 16045346]
[22]
Głuszyńska, A.; Juskowiak, B.; Kuta-Siejkowska, M.; Hoffmann, M.; Haider, S. Carbazole derivatives’ binding to c-KIT G-Quadruplex DNA. Molecules, 2018, 23(5), 1134.
[http://dx.doi.org/10.3390/molecules23051134] [PMID: 29747481]
[23]
Amato, J.; Madanayake, T.W.; Iaccarino, N.; Novellino, E.; Randazzo, A.; Hurley, L.H.; Pagano, B. HMGB1 binds to the KRAS promoter G-quadruplex: a new player in oncogene transcriptional regulation? Chem. Commun. (Camb.), 2018, 54(68), 9442-9445.
[http://dx.doi.org/10.1039/C8CC03614D] [PMID: 30079419]
[24]
Chu, B.; Zhang, D.; Paukstelis, P.J.A. Error! Hyperlink reference not valid. Nucleic Acids Res., 2019, 47, 11921-11930.
[PMID: 31724696]
[25]
Martiny-Baron, G.; Marmé, D. VEGF-mediated tumour angiogenesis: a new target for cancer therapy. Curr. Opin. Biotechnol., 1995, 6(6), 675-680.
[http://dx.doi.org/10.1016/0958-1669(95)80111-1] [PMID: 8527839]
[26]
Burge, S.; Parkinson, G.N.; Hazel, P.; Todd, A.K.; Neidle, S. Quadruplex DNA: sequence, topology and structure. Nucleic Acids Res., 2006, 34(19), 5402-5415.
[http://dx.doi.org/10.1093/nar/gkl655] [PMID: 17012276]
[27]
Winnerdy, F.R.; Bakalar, B.; Maity, A.; Vandana, J.J.; Mechulam, Y.; Schmitt, E.; Phan, A.T. NMR solution and X-ray crystal structures of a DNA molecule containing both right- and left-handed parallel-stranded G-quadruplexes. Nucleic Acids Res., 2019, 47(15), 8272-8281.
[http://dx.doi.org/10.1093/nar/gkz349] [PMID: 31216034]
[28]
Phillips, K.; Dauter, Z.; Murchie, A.I.; Lilley, D.M.; Luisi, B. The crystal structure of a parallel-stranded guanine tetraplex at 0.95 A resolution. J. Mol. Biol., 1997, 273(1), 171-182.
[http://dx.doi.org/10.1006/jmbi.1997.1292] [PMID: 9367755]
[29]
Oh, K-I.; Kim, J.; Park, C-J.; Lee, J-H. Dynamics studies of DNA with non-canonical structure using NMR spectroscopy. Int. J. Mol. Sci., 2020, 21(8), 2673.
[http://dx.doi.org/10.3390/ijms21082673] [PMID: 32290457]
[30]
Maity, A.; Winnerdy, F.R.; Chang, W.D.; Chen, G.; Phan, A.T. Intra-locked G-quadruplex structures formed by irregular DNA G-rich motifs. Nucleic Acids Res., 2020, 48(6), 3315-3327.
[http://dx.doi.org/10.1093/nar/gkaa008] [PMID: 32100003]
[31]
Bessi, I.; Jonker, H.R.A.; Richter, C.; Schwalbe, H. Involvement of long-lived intermediate states in the complex folding pathway of the human telomeric G-Quadruplex. Angew. Chem. Int. Ed. Engl., 2015, 54(29), 8444-8448.
[http://dx.doi.org/10.1002/anie.201502286] [PMID: 26036989]
[32]
Harkness, R.W.V., V; Mittermaier, A.K. G-register exchange dynamics in guanine quadruplexes. Nucleic Acids Res., 2016, 44(8), 3481-3494.
[http://dx.doi.org/10.1093/nar/gkw190] [PMID: 27060139]
[33]
Liu, H-Y.; Zhao, Q.; Zhang, T-P.; Wu, Y.; Xiong, Y-X.; Wang, S-K.; Ge, Y-L.; He, J-H.; Lv, P.; Ou, T-M.; Tan, J-H.; Li, D.; Gu, L-Q.; Ren, J.; Zhao, Y.; Huang, Z-S. Conformation selective antibody enables genome profiling and leads to discovery of parallel G-Quadruplex in human telomeres. Cell Chem. Biol., 2016, 23(10), 1261-1270.
[http://dx.doi.org/10.1016/j.chembiol.2016.08.013] [PMID: 27693060]
[34]
Phan, A.T.; Patel, D.J. Two-repeat human telomeric d(TAGGGTTAGGGT) sequence forms interconverting parallel and antiparallel G-quadruplexes in solution: distinct topologies, thermodynamic properties, and folding/unfolding kinetics. J. Am. Chem. Soc., 2003, 125(49), 15021-15027.
[http://dx.doi.org/10.1021/ja037616j] [PMID: 14653736]
[35]
Ambrus, A.; Chen, D.; Dai, J.; Bialis, T.; Jones, R.A.; Yang, D. Human telomeric sequence forms a hybrid-type intramolecular G-quadruplex structure with mixed parallel/antiparallel strands in potassium solution. Nucleic Acids Res., 2006, 34(9), 2723-2735.
[http://dx.doi.org/10.1093/nar/gkl348] [PMID: 16714449]
[36]
Ma, G.; Yu, Z.; Zhou, W.; Li, Y.; Fan, L.; Li, X. Investigation of Na+ and K+ competitively binding with a G-quadruplex and discovery of a stable K+–Na+-quadruplex. J. Phys. Chem. B, 2019, 123(26), 5405-5411.
[http://dx.doi.org/10.1021/acs.jpcb.9b02823] [PMID: 31244096]
[37]
Balkwill, G.D.; Garner, T.P.; Williams, H.E.L.; Searle, M.S. Folding topology of a bimolecular DNA quadruplex containing a stable mini-hairpin motif within the diagonal loop. J. Mol. Biol., 2009, 385(5), 1600-1615.
[http://dx.doi.org/10.1016/j.jmb.2008.11.050] [PMID: 19070621]
[38]
Li, X.; Sánchez-Ferrer, A.; Bagnani, M.; Adamcik, J.; Azzari, P.; Hao, J.; Song, A.; Liu, H.; Mezzenga, R. Metal ions confinement defines the architecture of G-quartet, G-quadruplex fibrils and their assembly into nematic tactoids. Proc. Natl. Acad. Sci. USA, 2020, 117(18), 9832-9839.
[http://dx.doi.org/10.1073/pnas.1919777117] [PMID: 32317383]
[39]
Bhattacharyya, D.; Mirihana Arachchilage, G.; Basu, S. Metal cations in G-quadruplex folding and stability. Front Chem., 2016, 4, 38.
[http://dx.doi.org/10.3389/fchem.2016.00038] [PMID: 27668212]
[40]
Lane, A.N.; Chaires, J.B.; Gray, R.D.; Trent, J.O. Stability and kinetics of G-quadruplex structures. Nucleic Acids Res., 2008, 36(17), 5482-5515.
[http://dx.doi.org/10.1093/nar/gkn517] [PMID: 18718931]
[41]
Wong, A.; Wu, G. Selective binding of monovalent cations to the stacking G-quartet structure formed by guanosine 5′-monophosphate: a solid-state NMR study. J. Am. Chem. Soc., 2003, 125(45), 13895-13905.
[http://dx.doi.org/10.1021/ja0302174] [PMID: 14599230]
[42]
Kotch, F.W.; Fettinger, J.C.; Davis, J.T. A lead-filled G-quadruplex: insight into the G-Quartet’s selectivity for Pb(2+) over K(+). Org. Lett., 2000, 2(21), 3277-3280.
[http://dx.doi.org/10.1021/ol0065120] [PMID: 11029189]
[43]
Largy, E.; Mergny, J-L.; Gabelica, V. Role of alkali metal ions in G-quadruplex nucleic acid structure and stability. Met. Ions Life Sci., 2016, 16, 203-258.
[http://dx.doi.org/10.1007/978-3-319-21756-7_7] [PMID: 26860303]
[44]
Zaccaria, F.; Paragi, G.; Fonseca Guerra, C. The role of alkali metal cations in the stabilization of guanine quadruplexes: why K(+) is the best. Phys. Chem. Chem. Phys., 2016, 18(31), 20895-20904.
[http://dx.doi.org/10.1039/C6CP01030J] [PMID: 27185388]
[45]
Yu, Z.; Zhou, W.; Han, J.; Li, Y.; Fan, L.; Li, X. Na+-induced conformational change of Pb2+-stabilized G-quadruplex and its influence on Pb2+ detection. Anal. Chem., 2016, 88(19), 9375-9380.
[http://dx.doi.org/10.1021/acs.analchem.6b02466] [PMID: 27589677]
[46]
Kankia, B.I.; Marky, L.A. Folding of the thrombin aptamer into a G-quadruplex with Sr(2+): stability, heat, and hydration. J. Am. Chem. Soc., 2001, 123(44), 10799-10804.
[http://dx.doi.org/10.1021/ja010008o] [PMID: 11686680]
[47]
Włodarczyk, A.; Grzybowski, P.; Patkowski, A.; Dobek, A. Effect of ions on the polymorphism, effective charge, and stability of human telomeric DNA. Photon correlation spectroscopy and circular dichroism studies. J. Phys. Chem. B, 2005, 109(8), 3594-3605.
[http://dx.doi.org/10.1021/jp045274d] [PMID: 16851398]
[48]
Hardin, C.C.; Watson, T.; Corregan, M.; Bailey, C. Cation-dependent transition between the quadruplex and Watson-Crick hairpin forms of d(CGCG3GCG). Biochemistry, 1992, 31(3), 833-841.
[http://dx.doi.org/10.1021/bi00118a028] [PMID: 1731941]
[49]
Lu, H.; Li, S.; Chen, J.; Xia, J.; Zhang, J.; Huang, Y.; Liu, X.; Wu, H.C.; Zhao, Y.; Chai, Z.; Hu, Y. Metal ions modulate the conformation and stability of a G-quadruplex with or without a small-molecule ligand. Metallomics, 2015, 7(11), 1508-1514.
[http://dx.doi.org/10.1039/C5MT00188A] [PMID: 26381587]
[50]
Kwan, I.C.M.; She, Y-M.; Wu, G. Trivalent lanthanide metal ions promote formation of stacking G-quartets. Chem. Commun. (Camb.), 2007, 41(41), 4286-4288.
[http://dx.doi.org/10.1039/b710299b] [PMID: 18217607]
[51]
Ou, T-M.; Lu, Y-J.; Tan, J-H.; Huang, Z-S.; Wong, K-Y.; Gu, L-Q. G-quadruplexes: targets in anticancer drug design. ChemMedChem, 2008, 3(5), 690-713.
[http://dx.doi.org/10.1002/cmdc.200700300] [PMID: 18236491]
[52]
Ruan, T.L.; Davis, S.J.; Powell, B.M.; Harbeck, C.P.; Habdas, J.; Habdas, P.; Yatsunyk, L.A. Lowering the overall charge on TMPyP4 improves its selectivity for G-quadruplex DNA. Biochimie, 2017, 132, 121-130.
[http://dx.doi.org/10.1016/j.biochi.2016.11.003] [PMID: 27840085]
[53]
Siddiqui-Jain, A.; Grand, C.L.; Bearss, D.J.; Hurley, L.H. Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription. Proc. Natl. Acad. Sci. USA, 2002, 99(18), 11593-11598.
[http://dx.doi.org/10.1073/pnas.182256799] [PMID: 12195017]
[54]
Caterino, M.; D’Aria, F.; Kustov, A.V.; Belykh, D.V.; Khudyaeva, I.S.; Starseva, O.M.; Berezin, D.B.; Pylina, Y.I.; Usacheva, T.; Amato, J.; Giancola, C. Selective binding of a bioactive porphyrin-based photosensitizer to the G-quadruplex from the KRAS oncogene promoter. Int. J. Biol. Macromol., 2020, 145, 244-251.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.12.152] [PMID: 31870869]
[55]
Han, H.; Langley, D.R.; Rangan, A.; Hurley, L.H. Selective interactions of cationic porphyrins with G-quadruplex structures. J. Am. Chem. Soc., 2001, 123(37), 8902-8913.
[http://dx.doi.org/10.1021/ja002179j] [PMID: 11552797]
[56]
Zhang, H.; Xiao, X.; Wang, P.; Pang, S.; Qu, F.; Ai, X.; Zhang, J. Conformational conversion of DNA G-quadruplex induced by a cationic porphyrin. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2009, 74(1), 243-247.
[http://dx.doi.org/10.1016/j.saa.2009.06.018] [PMID: 19577954]
[57]
Han, F.X.; Wheelhouse, R.T.; Hurley, L.H. Interactions of TMPyP4 and TMPyP2 with Quadruplex DNA. Structural basis for the differential effects on telomerase inhibition. J. Am. Chem. Soc., 1999, 121, 3561-3570.
[http://dx.doi.org/10.1021/ja984153m]
[58]
Shi, D-F.; Wheelhouse, R.T.; Sun, D.; Hurley, L.H. Quadruplex-interactive agents as telomerase inhibitors: synthesis of porphyrins and structure-activity relationship for the inhibition of telomerase. J. Med. Chem., 2001, 44(26), 4509-4523.
[http://dx.doi.org/10.1021/jm010246u] [PMID: 11741471]
[59]
Wu, X.; Maizels, N. Substrate-specific inhibition of RecQ helicase. Nucleic Acids Res., 2001, 29(8), 1765-1771.
[http://dx.doi.org/10.1093/nar/29.8.1765] [PMID: 11292849]
[60]
Cogoi, S.; Xodo, L.E. G-quadruplex formation within the promoter of the KRAS proto-oncogene and its effect on transcription. Nucleic Acids Res., 2006, 34(9), 2536-2549.
[http://dx.doi.org/10.1093/nar/gkl286] [PMID: 16687659]
[61]
Mikami-Terao, Y.; Akiyama, M.; Yuza, Y.; Yanagisawa, T.; Yamada, O.; Yamada, H. Antitumor activity of G-quadruplex-interactive agent TMPyP4 in K562 leukemic cells. Cancer Lett., 2008, 261(2), 226-234.
[http://dx.doi.org/10.1016/j.canlet.2007.11.017] [PMID: 18096315]
[62]
Fujimori, J.; Matsuo, T.; Shimose, S.; Kubo, T.; Ishikawa, M.; Yasunaga, Y.; Ochi, M. Antitumor effects of telomerase inhibitor TMPyP4 in osteosarcoma cell lines. J. Orthop. Res., 2011, 29(11), 1707-1711.
[http://dx.doi.org/10.1002/jor.21451] [PMID: 21590716]
[63]
Rapozzi, V.; Zorzet, S.; Zacchigna, M.; Della Pietra, E.; Cogoi, S.; Xodo, L.E. Anticancer activity of cationic porphyrins in melanoma tumour-bearing mice and mechanistic in vitro studies. Mol. Cancer, 2014, 13, 75.
[http://dx.doi.org/10.1186/1476-4598-13-75] [PMID: 24684778]
[64]
Neidle, S. Quadruplex nucleic acids as targets for anticancer therapeutics. Nat. Rev. Chem., 2017, 1, 41.
[http://dx.doi.org/10.1038/s41570-017-0041]
[65]
Guliaev, A.B.; Leontis, N.B. Cationic 5,10,15,20-tetrakis( N -methylpyridinium-4-yl)porphyrin fully intercalates at 5′-CG-3′ steps of duplex DNA in solution. Biochemistry, 1999, 38(47), 15425-15437.
[http://dx.doi.org/10.1021/bi9913808] [PMID: 10569925]
[66]
Kim, J-O.; Lee, Y-A.; Yun, B.H.; Han, S.W.; Kwag, S.T.; Kim, S.K. Binding of meso-tetrakis( N -methylpyridinium-4-yl)porphyrin to AT oligomers: effect of chain length and the location of the porphyrin stacking. Biophys. J., 2004, 86(2), 1012-1017.
[http://dx.doi.org/10.1016/S0006-3495(04)74176-4] [PMID: 14747336]
[67]
Taka, T.; Huang, L.; Wongnoppavich, A.; Tam-Chang, S-W.; Lee, T.R.; Tuntiwechapikul, W. Telomere shortening and cell senescence induced by perylene derivatives in A549 human lung cancer cells. Bioorg. Med. Chem., 2013, 21(4), 883-890.
[http://dx.doi.org/10.1016/j.bmc.2012.12.020] [PMID: 23321015]
[68]
Han, H.; Bennett, R.J.; Hurley, L.H. Inhibition of unwinding of G-quadruplex structures by Sgs1 helicase in the presence of N,N ′-bis[2-(1-piperidino)ethyl]-3,4,9,10-perylenetetracarboxylic diimide, a G-quadruplex-interactive ligand. Biochemistry, 2000, 39(31), 9311-9316.
[http://dx.doi.org/10.1021/bi000482r] [PMID: 10924124]
[69]
Rangan, A.; Fedoroff, O.Y.; Hurley, L.H. Induction of duplex to G-quadruplex transition in the c-myc promoter region by a small molecule. J. Biol. Chem., 2001, 276(7), 4640-4646.
[http://dx.doi.org/10.1074/jbc.M005962200] [PMID: 11035006]
[70]
Porru, M.; Artuso, S.; Salvati, E.; Bianco, A.; Franceschin, M.; Diodoro, M.G.; Passeri, D.; Orlandi, A.; Savorani, F.; D’Incalci, M.; Biroccio, A.; Leonetti, C. Targeting G-Quadruplex DNA structures by EMICORON has a strong antitumor efficacy against advanced models of human colon cancer. Mol. Cancer Ther., 2015, 14(11), 2541-2551.
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0253] [PMID: 26304235]
[71]
Franceschin, M.; Rizzo, A.; Casagrande, V.; Salvati, E.; Alvino, A.; Altieri, A.; Ciammaichella, A.; Iachettini, S.; Leonetti, C.; Ortaggi, G.; Porru, M.; Bianco, A.; Biroccio, A. Aromatic core extension in the series of N -cyclic bay-substituted perylene G-quadruplex ligands: increased telomere damage, antitumor activity, and strong selectivity for neoplastic over healthy cells. ChemMedChem, 2012, 7(12), 2144-2154.
[http://dx.doi.org/10.1002/cmdc.201200348] [PMID: 23097341]
[72]
Micheli, E.; Altieri, A.; Cianni, L.; Cingolani, C.; Iachettini, S.; Bianco, A.; Leonetti, C.; Cacchione, S.; Biroccio, A.; Franceschin, M.; Rizzo, A. Perylene and coronene derivatives binding to G-rich promoter oncogene sequences efficiently reduce their expression in cancer cells. Biochimie, 2016, 125, 223-231.
[http://dx.doi.org/10.1016/j.biochi.2016.04.008] [PMID: 27086081]
[73]
Gilbert-Girard, S.; Gravel, A.; Artusi, A.; Richter, S.N.; Wallaschek, N.; Kaufer, B.B.; Flamand, L. Error! Hyperlink reference not valid. J. Virol., 2021, 91, e00402.
[PMID: 28468887]
[74]
Burger, A.M.; Dai, F.; Schultes, C.M.; Reszka, A.P.; Moore, M.J.; Double, J.A.; Neidle, S. The G-quadruplex-interactive molecule BRACO-19 inhibits tumor growth, consistent with telomere targeting and interference with telomerase function. Cancer Res., 2005, 65(4), 1489-1496.
[http://dx.doi.org/10.1158/0008-5472.CAN-04-2910] [PMID: 15735037]
[75]
Lagah, S.; Tan, I-L.; Radhakrishnan, P.; Hirst, R.A.; Ward, J.H.; O’Callaghan, C.; Smith, S.J.; Stevens, M.F.G.; Grundy, R.G.; Rahman, R. RHPS4 G-quadruplex ligand induces anti-proliferative effects in brain tumor cells. PLoS One, 2014, 9(1), e86187.
[http://dx.doi.org/10.1371/journal.pone.0086187] [PMID: 24454961]
[76]
Kim, J.; Jones-Hall, Y.L.; Wei, R.; Myers, J.; Qi, Y.; Knipp, G.T.; Liu, W. Association between hTERT rs2736100 polymorphism and sensitivity to anti-cancer agents. Front. Genet., 2013, 4, 162.
[http://dx.doi.org/10.3389/fgene.2013.00162] [PMID: 23986774]
[77]
Incles, C.M.; Schultes, C.M.; Kempski, H.; Koehler, H.; Kelland, L.R.; Neidle, S. Error! Hyperlink reference not valid. Mol. Cancer Ther., 2004, 3, 1201-1206.
[PMID: 15486186]
[78]
Gowan, S.M.; Harrison, J.R.; Patterson, L.; Valenti, M.; Read, M.A.; Neidle, S.; Kelland, L.R. A G-quadruplex-interactive potent small-molecule inhibitor of telomerase exhibiting in vitro and in vivo antitumor activity. Mol. Pharmacol., 2002, 61(5), 1154-1162.
[http://dx.doi.org/10.1124/mol.61.5.1154] [PMID: 11961134]
[79]
Kelland, L.R. Overcoming the immortality of tumour cells by telomere and telomerase based cancer therapeutics--current status and future prospects. Eur. J. Cancer, 2005, 41(7), 971-979.
[http://dx.doi.org/10.1016/j.ejca.2004.11.024] [PMID: 15862745]
[80]
Iachettini, S.; Stevens, M.F.; Frigerio, M.; Hummersone, M.G.; Hutchinson, I.; Garner, T.P.; Searle, M.S.; Wilson, D.W.; Munde, M.; Nanjunda, R.; D’Angelo, C.; Zizza, P.; Rizzo, A.; Cingolani, C.; De Cicco, F.; Porru, M.; D’Incalci, M.; Leonetti, C.; Biroccio, A.; Salvati, E. On and off-target effects of telomere uncapping G-quadruplex selective ligands based on pentacyclic acridinium salts. J. Exp. Clin. Cancer Res., 2013, 32(1), 68.
[http://dx.doi.org/10.1186/1756-9966-32-68] [PMID: 24330541]
[81]
Shin-ya, K.; Wierzba, K.; Matsuo, K.; Ohtani, T.; Yamada, Y.; Furihata, K.; Hayakawa, Y.; Seto, H. Telomestatin, a novel telomerase inhibitor from Streptomyces anulatus. J. Am. Chem. Soc., 2001, 123(6), 1262-1263.
[http://dx.doi.org/10.1021/ja005780q] [PMID: 11456694]
[82]
Monchaud, D.; Granzhan, A.; Saettel, N.; Guédin, A.; Mergny, J-L.; Teulade-Fichou, M-P. “One ring to bind them all”-part I: the efficiency of the macrocyclic scaffold for g-quadruplex DNA recognition. J. Nucleic Acids, 2010, 2010, 525862.
[http://dx.doi.org/10.4061/2010/525862] [PMID: 20725629]
[83]
Iida, K.; Nagasawa, K. Macrocyclic polyoxazoles as G-quadruplex ligands. Chem. Rec., 2013, 13(6), 539-548.
[http://dx.doi.org/10.1002/tcr.201300015] [PMID: 24347328]
[84]
Kim, M-Y.; Vankayalapati, H.; Shin-Ya, K.; Wierzba, K.; Hurley, L.H. Telomestatin, a potent telomerase inhibitor that interacts quite specifically with the human telomeric intramolecular g-quadruplex. J. Am. Chem. Soc., 2002, 124(10), 2098-2099.
[http://dx.doi.org/10.1021/ja017308q] [PMID: 11878947]
[85]
Chung, W.J.; Heddi, B.; Tera, M.; Iida, K.; Nagasawa, K.; Phan, A.T. Solution structure of an intramolecular (3 + 1) human telomeric G-quadruplex bound to a telomestatin derivative. J. Am. Chem. Soc., 2013, 135(36), 13495-13501.
[http://dx.doi.org/10.1021/ja405843r] [PMID: 23909929]
[86]
Gomez, D.; O’Donohue, M-F.; Wenner, T.; Douarre, C.; Macadré, J.; Koebel, P.; Giraud-Panis, M-J.; Kaplan, H.; Kolkes, A.; Shin-ya, K.; Riou, J-F. The G-quadruplex ligand telomestatin inhibits POT1 binding to telomeric sequences in vitro and induces GFP-POT1 dissociation from telomeres in human cells. Cancer Res., 2006, 66(14), 6908-6912.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-1581] [PMID: 16849533]
[87]
Gomez, D.; Wenner, T.; Brassart, B.; Douarre, C.; O’Donohue, M-F.; El Khoury, V.; Shin-Ya, K.; Morjani, H.; Trentesaux, C.; Riou, J-F. Telomestatin-induced telomere uncapping is modulated by POT1 through G-overhang extension in HT1080 human tumor cells. J. Biol. Chem., 2006, 281(50), 38721-38729.
[http://dx.doi.org/10.1074/jbc.M605828200] [PMID: 17050546]
[88]
Tahara, H.; Shin-Ya, K.; Seimiya, H.; Yamada, H.; Tsuruo, T.; Ide, T. G-Quadruplex stabilization by telomestatin induces TRF2 protein dissociation from telomeres and anaphase bridge formation accompanied by loss of the 3′ telomeric overhang in cancer cells. Oncogene, 2006, 25(13), 1955-1966.
[http://dx.doi.org/10.1038/sj.onc.1209217] [PMID: 16302000]
[89]
Tauchi, T.; Shin-ya, K.; Sashida, G.; Sumi, M.; Okabe, S.; Ohyashiki, J.H.; Ohyashiki, K. Telomerase inhibition with a novel G-quadruplex-interactive agent, telomestatin: in vitro and in vivo studies in acute leukemia. Oncogene, 2006, 25(42), 5719-5725.
[http://dx.doi.org/10.1038/sj.onc.1209577] [PMID: 16652154]
[90]
Micco, M.; Collie, G.W.; Dale, A.G.; Ohnmacht, S.A.; Pazitna, I.; Gunaratnam, M.; Reszka, A.P.; Neidle, S. Structure-based design and evaluation of naphthalene diimide G-quadruplex ligands as telomere targeting agents in pancreatic cancer cells. J. Med. Chem., 2013, 56(7), 2959-2974.
[http://dx.doi.org/10.1021/jm301899y] [PMID: 23514618]
[91]
Ohnmacht, S.A.; Marchetti, C.; Gunaratnam, M.; Besser, R.J.; Haider, S.M.; Di Vita, G.; Lowe, H.L.; Mellinas-Gomez, M.; Diocou, S.; Robson, M.; Šponer, J.; Islam, B.; Pedley, R.B.; Hartley, J.A.; Neidle, S. A G-quadruplex-binding compound showing anti-tumour activity in an in vivo model for pancreatic cancer. Sci. Rep., 2015, 5, 11385.
[http://dx.doi.org/10.1038/srep11385] [PMID: 26077929]
[92]
Neidle, S. Human telomeric G-quadruplex: the current status of telomeric G-quadruplexes as therapeutic targets in human cancer. FEBS J., 2010, 277(5), 1118-1125.
[http://dx.doi.org/10.1111/j.1742-4658.2009.07463.x] [PMID: 19951354]
[93]
Carvalho, J.; Mergny, J-L.; Salgado, G.F.; Queiroz, J.A.; Cruz, C. G-quadruplex, friend or foe: The role of the g-quartet in anticancer strategies. Trends Mol. Med., 2020, 26(9), 848-861.
[http://dx.doi.org/10.1016/j.molmed.2020.05.002] [PMID: 32467069]
[94]
Balasubramanian, S.; Hurley, L.H.; Neidle, S. Targeting G-quadruplexes in gene promoters: a novel anticancer strategy? Nat. Rev. Drug Discov., 2011, 10(4), 261-275.
[http://dx.doi.org/10.1038/nrd3428] [PMID: 21455236]
[95]
Ali, A.; Bhattacharya, S. DNA binders in clinical trials and chemotherapy. Bioorg. Med. Chem., 2014, 22(16), 4506-4521.
[http://dx.doi.org/10.1016/j.bmc.2014.05.030] [PMID: 24947479]
[96]
Leijen, S.; van Geel, R.M.J.M.; Sonke, G.S.; de Jong, D.; Rosenberg, E.H.; Marchetti, S.; Pluim, D.; van Werkhoven, E.; Rose, S.; Lee, M.A.; Freshwater, T.; Beijnen, J.H.; Schellens, J.H.M. Phase II study of WEE1 inhibitor AZD1775 plus carboplatin in patients with TP53-mutated ovarian cancer refractory or resistant to first-line therapy within 3 months. J. Clin. Oncol., 2016, 34(36), 4354-4361.
[http://dx.doi.org/10.1200/JCO.2016.67.5942] [PMID: 27998224]
[97]
Bruijnincx, P.C.A.; Sadler, P.J. New trends for metal complexes with anticancer activity. Curr. Opin. Chem. Biol., 2008, 12(2), 197-206.
[http://dx.doi.org/10.1016/j.cbpa.2007.11.013] [PMID: 18155674]
[98]
Mouriño, V.; Cattalini, J.P.; Boccaccini, A.R. Metallic ions as therapeutic agents in tissue engineering scaffolds: an overview of their biological applications and strategies for new developments. J. R. Soc. Interface, 2012, 9(68), 401-419.
[http://dx.doi.org/10.1098/rsif.2011.0611] [PMID: 22158843]
[99]
Chen, Q.Y.; DesMarais, T.; Costa, M. Metals and mechanisms of carcinogenesis. Annu. Rev. Pharmacol. Toxicol., 2019, 59, 537-554.
[http://dx.doi.org/10.1146/annurev-pharmtox-010818-021031] [PMID: 30625284]
[100]
Spessard, G.O.; Meissler, G.L. Organometallic Chemistry, 2nd ed; , 2010.
[101]
van Staveren, D.R.; Metzler-Nolte, N. Bioorganometallic chemistry of ferrocene. Chem. Rev., 2004, 104(12), 5931-5985.
[http://dx.doi.org/10.1021/cr0101510] [PMID: 15584693]
[102]
Cao, Q.; Li, Y.; Freisinger, E.; Qin, P.Z.; Sigel, R.K.O.; Mao, Z-W. G-quadruplex DNA targeted metal complexes acting as potential anticancer drugs. Inorg. Chem. Front., 2017, 4, 10-32.
[http://dx.doi.org/10.1039/C6QI00300A]
[103]
Georgiades, S.N.; Abd Karim, N.H.; Suntharalingam, K.; Vilar, R. Interaction of metal complexes with G-quadruplex DNA. Angew. Chem. Int. Ed. Engl., 2010, 49(24), 4020-4034.
[http://dx.doi.org/10.1002/anie.200906363] [PMID: 20503216]
[104]
Haas, K.L.; Franz, K.J. Application of metal coordination chemistry to explore and manipulate cell biology. Chem. Rev., 2009, 109(10), 4921-4960.
[http://dx.doi.org/10.1021/cr900134a] [PMID: 19715312]
[105]
Papadopoulos, K.; Mita, A.; Ricart, A.; Hufnagel, D.; Northfelt, D.; Von Hoff, D.; Darjania, L.; Lim, J.; Padgett, C.; Marschke, R. Error! Hyperlink reference not valid. Mol. Cancer Ther., 2007, 6, B93.
[106]
Yang, H.; Zhou, Y.; Liu, J. G-quadruplex DNA for construction of biosensors. Trends Analyt. Chem., 2020, 132, 1-13.
[http://dx.doi.org/10.1016/j.trac.2020.116060]
[107]
McQuaid, K.; Abell, H.; Gurung, S.P.; Allan, D.R.; Winter, G.; Sorensen, T.; Cardin, D.J.; Brazier, J.A.; Cardin, C.J.; Hall, J.P. Structural studies reveal enantiospecific recognition of a DNA G-Quadruplex by a ruthenium polypyridyl complex. Angew. Chem. Int. Ed. Engl., 2019, 58(29), 9881-9885.
[http://dx.doi.org/10.1002/anie.201814502] [PMID: 30958918]
[108]
Kench, T.; Vilar, R. Metal complexes as G-quadruplex binders. In: Quadruplex Nucleic Acids As Targets For Medicinal Chemistry; Neidle Academic Press Elsevier Science, 2020; 54, pp. 485-515.
[http://dx.doi.org/10.1016/bs.armc.2020.05.004]
[109]
Saraswati, A.P.; Relitti, N.; Brindisi, M.; Gemma, S.; Zisterer, D.; Butini, S.; Campiani, G. Raising the bar in anticancer therapy: recent advances in, and perspectives on, telomerase inhibitors. Drug Discov. Today, 2019, 24(7), 1370-1388.
[http://dx.doi.org/10.1016/j.drudis.2019.05.015] [PMID: 31136800]
[110]
Weynand, J.; Diman, A.; Abraham, M.; Marcélis, L.; Jamet, H.; Decottignies, A.; Dejeu, J.; Defrancq, E.; Elias, B. Towards the development of photo-reactive ruthenium(II) complexes targeting telomeric G-Quadruplex DNA. Chemistry, 2018, 24(72), 19216-19227.
[http://dx.doi.org/10.1002/chem.201804771] [PMID: 30362627]
[111]
Suntharalingam, K.; Vilar, R. Recognition of G-quadruplexes By Metal Complexes. In: Guanine Quartets: Structure And Application; Spindler, L.; Fritzsche, W., Eds.; , 2012; pp. 263-274.
[http://dx.doi.org/10.1039/9781849736954-00263]
[112]
Kwok, C.K.; Merrick, C.J. G-Quadruplexes: Prediction, characterization, and biological application. Trends Biotechnol., 2017, 35(10), 997-1013.
[http://dx.doi.org/10.1016/j.tibtech.2017.06.012] [PMID: 28755976]
[113]
Piraux, G.; Bar, L.; Abraham, M.; Lavergne, T.; Jamet, H.; Dejeu, J.; Marcélis, L.; Defrancq, E.; Elias, B. New ruthenium-based probes for selective G-Quadruplex targeting. Chemistry, 2017, 23(49), 11872-11880.
[http://dx.doi.org/10.1002/chem.201702076] [PMID: 28609545]
[114]
Wang, X.; Pei, L.; Fan, X.; Shi, S. [Ru(L)2(3-tppp)]2+ (L = bpy, phen) stabilizes two different forms of the human telomeric G-quadruplex DNA. Inorg. Chem. Commun., 2016, 72, 7-12.
[http://dx.doi.org/10.1016/j.inoche.2016.07.010]
[115]
Bouzada, D.; Salvadó, I.; Barka, G.; Rama, G.; Martínez-Costas, J.; Lorca, R.; Somoza, Á.; Melle-Franco, M.; Vázquez, M.E.; Vázquez López, M. Selective G-quadruplex binding by oligoarginine-Ru(dppz) metallopeptides. Chem. Commun. (Camb.), 2018, 54(6), 658-661.
[http://dx.doi.org/10.1039/C7CC08286J] [PMID: 29300399]
[116]
Kloss, A.; Henklein, P.; Siele, D.; Schmolke, M.; Apcher, S.; Kuehn, L.; Sheppard, P.W.; Dahlmann, B. The cell-penetrating peptide octa-arginine is a potent inhibitor of proteasome activities. Eur. J. Pharm. Biopharm., 2009, 72(1), 219-225.
[http://dx.doi.org/10.1016/j.ejpb.2008.10.016] [PMID: 19027853]
[117]
He, L.; Chen, X.; Meng, Z.; Wang, J.; Tian, K.; Li, T.; Shao, F. Octahedral ruthenium complexes selectively stabilize G-quadruplexes. Chem. Commun. (Camb.), 2016, 52(52), 8095-8098.
[http://dx.doi.org/10.1039/C6CC03117J] [PMID: 27265243]
[118]
Łęczkowska, A.; Gonzalez-Garcia, J.; Perez-Arnaiz, C.; Garcia, B.; White, A.J.P.; Vilar, R. Binding studies of metal–salphen and metal–bipyridine complexes towards G-Quadruplex DNA. Chemistry, 2018, 24(45), 11785-11794.
[http://dx.doi.org/10.1002/chem.201802248] [PMID: 29897148]
[119]
Campbell, N.H.; Karim, N.H.A.; Parkinson, G.N.; Gunaratnam, M.; Petrucci, V.; Todd, A.K.; Vilar, R.; Neidle, S. Molecular basis of structure-activity relationships between salphen metal complexes and human telomeric DNA quadruplexes. J. Med. Chem., 2012, 55(1), 209-222.
[http://dx.doi.org/10.1021/jm201140v] [PMID: 22112241]
[120]
Arjmand, F.; Sharma, S.; Parveen, S.; Toupet, L.; Yu, Z.; Cowan, J.A. Copper(ii) l/d-valine-(1,10-phen) complexes target human telomeric G-quadruplex motifs and promote site-specific DNA cleavage and cellular cytotoxicity. Dalton Trans., 2020, 49(28), 9888-9899.
[http://dx.doi.org/10.1039/D0DT01527J] [PMID: 32638779]
[121]
Xiong, Y-X.; Huang, Z-S.; Tan, J-H. Targeting G-quadruplex nucleic acids with heterocyclic alkaloids and their derivatives. Eur. J. Med. Chem., 2015, 97, 538-551.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.021] [PMID: 25466923]
[122]
Qin, Q-P.; Qin, J-L.; Meng, T.; Yang, G-A.; Wei, Z-Z.; Liu, Y-C.; Liang, H.; Chen, Z-F. Preparation of 6/8/11-Amino/Chloro-Oxoisoaporphine and Group-10 metal complexes and evaluation of their in vitro and in vivo antitumor activity. Sci. Rep., 2016, 6, 37644.
[http://dx.doi.org/10.1038/srep37644] [PMID: 27898051]
[123]
Wei, Z-Z.; Qin, Q-P.; Meng, T.; Deng, C-X.; Liang, H.; Chen, Z-F. 5-Bromo-oxoisoaporphine platinum(II) complexes exhibit tumor cell cytotoxcicity via inhibition of telomerase activity and disruption of c-myc G-quadruplex DNA and mitochondrial functions. Eur. J. Med. Chem., 2018, 145, 360-369.
[http://dx.doi.org/10.1016/j.ejmech.2017.12.092] [PMID: 29335202]
[124]
Chen, Z-F.; Qin, Q-P.; Qin, J-L.; Liu, Y-C.; Huang, K-B.; Li, Y-L.; Meng, T.; Zhang, G-H.; Peng, Y.; Luo, X-J.; Liang, H. Stabilization of G-quadruplex DNA, inhibition of telomerase activity, and tumor cell apoptosis by organoplatinum(II) complexes with oxoisoaporphine. J. Med. Chem., 2015, 58(5), 2159-2179.
[http://dx.doi.org/10.1021/jm5012484] [PMID: 25650792]
[125]
Qin, J-L.; Qin, Q-P.; Wei, Z-Z.; Yu, Y-C.; Meng, T.; Wu, C-X.; Liang, Y-L.; Liang, H.; Chen, Z-F. Stabilization of c-myc G-Quadruplex DNA, inhibition of telomerase activity, disruption of mitochondrial functions and tumor cell apoptosis by platinum(II) complex with 9-amino-oxoisoaporphine. Eur. J. Med. Chem., 2016, 124, 417-427.
[http://dx.doi.org/10.1016/j.ejmech.2016.08.054] [PMID: 27597417]
[126]
Qin, Q-P.; Qin, J-L.; Meng, T.; Lin, W-H.; Zhang, C-H.; Wei, Z-Z.; Chen, J-N.; Liu, Y-C.; Liang, H.; Chen, Z-F. High in vivo antitumor activity of cobalt oxoisoaporphine complexes by targeting G-quadruplex DNA, telomerase and disrupting mitochondrial functions. Eur. J. Med. Chem., 2016, 124, 380-392.
[http://dx.doi.org/10.1016/j.ejmech.2016.08.063] [PMID: 27597414]

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