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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Mitochondria-Targeting Anticancer Metal Complexes

Author(s): Andrea Erxleben*

Volume 26, Issue 4, 2019

Page: [694 - 728] Pages: 35

DOI: 10.2174/0929867325666180307112029

Price: $65

Abstract

Background: Since the serendipitous discovery of the antitumor activity of cisplatin there has been a continuous surge in studies aimed at the development of new cytotoxic metal complexes. While the majority of these complexes have been designed to interact with nuclear DNA, other targets for anticancer metallodrugs attract increasing interest. In cancer cells the mitochondrial metabolism is deregulated. Impaired apoptosis, insensitivity to antigrowth signals and unlimited proliferation have been linked to mitochondrial dysfunction. It is therefore not surprising that mitochondria have emerged as a major target for cancer therapy. Mitochondria-targeting agents are able to bypass resistance mechanisms and to (re-) activate cell-death programs.

Methods: Web-based literature searching tools such as SciFinder were used to search for reports on cytotoxic metal complexes that are taken up by the mitochondria and interact with mitochondrial DNA or mitochondrial proteins, disrupt the mitochondrial membrane potential, facilitate mitochondrial membrane permeabilization or activate mitochondria-dependent celldeath signaling by unbalancing the cellular redox state. Included in the search were publications investigating strategies to selectively accumulate metallodrugs in the mitochondria.

Results: This review includes 241 references on antimitochondrial metal complexes, the use of mitochondria-targeting carrier ligands and the formation of lipophilic cationic complexes.

Conclusion: Recent developments in the design, cytotoxic potency, and mechanistic understanding of antimitochondrial metal complexes, in particular of cyclometalated Au, Ru, Ir and Pt complexes, Ru polypyridine complexes and Au-N-heterocyclic carbene and phosphine complexes are summarized and discussed.

Keywords: Anticancer, metallodrugs, mitochondria, apoptosis, thioredoxin reductase, translocator protein, reactive oxygen species, mitochondrial membrane potential.

[1]
Rosenberg, B.; Vancamp, L.; Krigas, T. Inhibition of cell division by electrolysis products from a platinum electrode. Nature, 1965, 205, 698-699.
[2]
Mjos, K.D.; Orvig, C. Metallodrugs in medicinal inorganic chemistry. Chem. Rev., 2014, 114(8), 4540-4563.
[3]
Barry, N.P.E.; Sadler, P.J. Exploration of the medical periodic table: towards new targets. Chem. Commun. (Camb.), 2013, 49(45), 5106-5131.
[4]
Gaynor, D.; Griffith, D.M. The prevalence of metal-based drugs as therapeutic or diagnostic agents: beyond platinum. Dalton Trans., 2012, 41(43), 13239-13257.
[5]
Johnstone, T.C.; Suntharalingam, K.; Lippard, S.J. The next generation of platinum drugs: targeted Pt(II) agents, nanoparticle delivery, and Pt(IV) prodrugs. Chem. Rev., 2016, 116(5), 3436-3486.
[6]
Komeda, S.; Casini, A. Next-generation anticancer metallodrugs. Curr. Top. Med. Chem., 2012, 12(3), 219-235.
[7]
Barnard, P.J.; Berners-Price, S.J. Targeting the mitochondrial cell death pathway with gold compounds. Coord. Chem. Rev., 2007, 251, 1889-1902.
[8]
Santini, C.; Pellei, M.; Gandin, V.; Porchia, M.; Tisato, F.; Marzano, C. Advances in copper complexes as anticancer agents. Chem. Rev., 2014, 114(1), 815-862.
[9]
Bergamo, A.; Sava, G. Ruthenium anticancer compounds: myths and realities of the emerging metal-based drugs. Dalton Trans., 2011, 40(31), 7817-7823.
[10]
Gorrini, C.; Harris, I.S.; Mak, T.W. Modulation of oxidative stress as an anticancer strategy. Nat. Rev. Drug Discov., 2013, 12(12), 931-947.
[11]
Bellance, N.; Lestienne, P.; Rossignol, R. Mitochondria: from bioenergetics to the metabolic regulation of carcinogenesis. Front. Biosci., 2009, 14, 4015-4034.
[12]
McFarland, R.; Taylor, R.W.; Turnbull, D.M. Mitochondrial disease--its impact, etiology, and pathology. Curr. Top. Dev. Biol., 2007, 77, 113-155.
[13]
Taylor, R.W.; Turnbull, D.M. Mitochondrial DNA mutations in human disease. Nat. Rev. Genet., 2005, 6(5), 389-402.
[14]
Indran, I.R.; Tufo, G.; Pervaiz, S.; Brenner, C. Recent advances in apoptosis, mitochondria and drug resistance in cancer cells. Biochim. Biophys. Acta, 2011, 1807(6), 735-745.
[15]
Kroemer, G.; Pouyssegur, J. Tumor cell metabolism: cancer’s Achilles’ heel. Cancer Cell, 2008, 13(6), 472-482.
[16]
Galluzzi, L.; Morselli, E.; Kepp, O.; Vitale, I.; Rigoni, A.; Vacchelli, E.; Michaud, M.; Zischka, H.; Castedo, M.; Kroemer, G. Mitochondrial gateways to cancer. Mol. Aspects Med., 2010, 31(1), 1-20.
[17]
Gogvadze, V.; Orrenius, S.; Zhivotovsky, B. Mitochondria in cancer cells: what is so special about them? Trends Cell Biol., 2008, 18(4), 165-173.
[18]
Mashima, T.; Tsuruo, T. Defects of the apoptotic pathway as therapeutic target against cancer. Drug Resist. Updat., 2005, 8(6), 339-343.
[19]
Galluzzi, L.; Larochette, N.; Zamzami, N.; Kroemer, G. Mitochondria as therapeutic targets for cancer chemotherapy. Oncogene, 2006, 25(34), 4812-4830.
[20]
Machida, K.; Ohta, Y.; Osada, H. Suppression of apoptosis by cyclophilin D via stabilization of hexokinase II mitochondrial binding in cancer cells. J. Biol. Chem., 2006, 281(20), 14314-14320.
[21]
Andrews, P.A.; Albright, K.D. Mitochondrial defects in cis-diamminedichloroplatinum(II)-resistant human ovarian carcinoma cells. Cancer Res., 1992, 52(7), 1895-1901.
[22]
Isonishi, S.; Saitou, M.; Yasuda, M.; Tanaka, T. Mitochondria in platinum resistant cells. Hum. Cell, 2001, 14(3), 203-210.
[23]
Hirama, M.; Isonishi, S.; Yasuda, M.; Ishikawa, H. Characterization of mitochondria in cisplatin-resistant human ovarian carcinoma cells. Oncol. Rep., 2006, 16(5), 997-1002.
[24]
Groessl, M.; Zava, O.; Dyson, P.J. Cellular uptake and subcellular distribution of ruthenium-based metallodrugs under clinical investigation versus cisplatin. Metallomics, 2011, 3(6), 591-599.
[25]
Chazotte, B. Labeling mitochondria with MitoTracker dyes. Cold Spring Harb. Protoc., 2011, 2011(8), 990-992.
[26]
Pröfrock, D.; Prange, A. Inductively coupled plasma-mass spectrometry (ICP-MS) for quantitative analysis in environmental and life sciences: a review of challenges, solutions, and trends. Appl. Spectrosc., 2012, 66(8), 843-868.
[27]
Cullen, K.J.; Yang, Z.; Schumaker, L.; Guo, Z. Mitochondria as a critical target of the chemotheraputic agent cisplatin in head and neck cancer. J. Bioenerg. Biomembr., 2007, 39(1), 43-50.
[28]
Murata, T.; Hibasami, H.; Maekawa, S.; Tagawa, T.; Nakashima, K. Preferential binding of cisplatin to mitochondrial DNA and suppression of ATP generation in human malignant melanoma cells. Biochem. Int., 1990, 20(5), 949-955.
[29]
Olivero, O.A.; Semino, C.; Kassim, A.; Lopez-Larraza, D.M.; Poirier, M.C. Preferential binding of cisplatin to mitochondrial DNA of Chinese hamster ovary cells. Mutat. Res., 1995, 346(4), 221-230.
[30]
Marrache, S.; Pathak, R.K.; Dhar, S. Detouring of cisplatin to access mitochondrial genome for overcoming resistance. Proc. Natl. Acad. Sci. USA, 2014, 111(29), 10444-10449.
[31]
Wisnovsky, S.P.; Wilson, J.J.; Radford, R.J.; Pereira, M.P.; Chan, M.R.; Laposa, R.R.; Lippard, S.J.; Kelley, S.O. Targeting mitochondrial DNA with a platinum-based anticancer agent. Chem. Biol., 2013, 20(11), 1323-1328.
[32]
Köster, S.D.; Alborzinia, H.; Can, S.; Kitanovic, I.; Wölfl, S.; Rubbiani, R.; Ott, I.; Riesterer, P.; Prokop, A.; Merz, K.; Metzler-Nolte, N. A spontaneous gold(I)-azide alkyne cycloaddition reaction yields gold-peptide bioconjugates which overcome cisplatin resistance in a p53-mutant cancer cell line. Chem. Sci. (Camb.), 2012, 3, 2062-2072.
[33]
Feldhaeusser, B.; Platt, S.R.; Marrache, S.; Kolishetti, N.; Pathak, R.K.; Montgomery, D.J.; Reno, L.R.; Howerth, E.; Dhar, S. Evaluation of nanoparticle delivered cisplatin in beagles. Nanoscale, 2015, 7(33), 13822-13830.
[34]
Zhou, W.; Wang, X.; Hu, M.; Zhu, C.; Guo, Z. A mitochondria-targeting copper complex exhibits potent cytotoxicity against cisplatin-resistant tumor cells through multiple mechanisms of action. Chem. Sci. (Camb.), 2014, 5, 2761-2770.
[35]
Banik, B.; Somyajit, K.; Nagaraju, G.; Chakravarty, A.R. Oxovanadium(IV) complexes of curcumin for cellular imaging and mitochondria targeted photocytotoxicity. Dalton Trans., 2014, 43(35), 13358-13369.
[36]
He, X.; Gong, L.; Kräling, K.; Gründler, K.; Frias, C.; Webster, R.D.; Meggers, E.; Prokop, A.; Xia, H. Unusual η2-allene osmacycle with apoptotic properties. ChemBioChem, 2010, 11(11), 1607-1613.
[37]
Koo, C-K.; So, L.K-Y.; Wong, K-L.; Ho, Y-M.; Lam, Y-W.; Lam, M.H-W.; Cheah, K-W.; Cheng, C.C-W.; Kwok, W-M. A triphenylphosphonium-functionalised cyclometalated platinum(II) complex as a nucleolus-specific two-photon molecular dye. Chemistry, 2010, 16(13), 3942-3950.
[38]
Hoye, A.T.; Davoren, J.E.; Wipf, P.; Fink, M.P.; Kagan, V.E. Targeting mitochondria. Acc. Chem. Res., 2008, 41(1), 87-97.
[39]
Eloy, L.; Jarrousse, A-S.; Teyssot, M-L.; Gautier, A.; Morel, L.; Jolivalt, C.; Cresteil, T.; Roland, S. Anticancer activity of silver-N-heterocyclic carbene complexes: caspase-independent induction of apoptosis via mitochondrial apoptosis-inducing factor (AIF). ChemMedChem, 2012, 7(5), 805-814.
[40]
Liu, J.J.; Galettis, P.; Farr, A.; Maharaj, L.; Samarasinha, H.; McGechan, A.C.; Baguley, B.C.; Bowen, R.J.; Berners-Price, S.J.; McKeage, M.J. In vitro antitumour and hepatotoxicity profiles of Au(I) and Ag(I) bidentate pyridyl phosphine complexes and relationships to cellular uptake. J. Inorg. Biochem., 2008, 102(2), 303-310.
[41]
Sun, R.W-Y.; Chow, A.L-F.; Li, X-H.; Yan, J.J.; Chui, S.S-Y.; Che, C-M. Luminescent cyclometalated platinum(II) complexes containing N-heterocyclic carbene ligands with potent in vitro and in vivo anti-cancer properties accumulate in cytoplasmic structures of cancer cells. Chem. Sci. (Camb.), 2011, 2, 728-736.
[42]
Erkkila, K.E.; Odom, D.T.; Barton, J.K. Recognition and reaction of metallointercalators with DNA. Chem. Rev., 1999, 99(9), 2777-2796.
[43]
Erxleben, A. . Advances in the development of DNAcleaving metal complexes as anticancer agents.Elsevier Reference Module in Chemistry, Molecular Sciences and Chemical Engineering., 30-Nov-2015
[44]
Gill, M.R.; Thomas, J.A. Ruthenium(II) polypyridyl complexes and DNA--from structural probes to cellular imaging and therapeutics. Chem. Soc. Rev., 2012, 41(8), 3179-3192.
[45]
Pisani, M.J.; Weber, D.K.; Heimann, K.; Collins, J.G.; Keene, F.R. Selective mitochondrial accumulation of cytotoxic dinuclear polypyridyl ruthenium(II) complexes. Metallomics, 2010, 2(6), 393-396.
[46]
Pisani, M.J.; Fromm, P.D.; Mulyana, Y.; Clarke, R.J.; Körner, H.; Heimann, K.; Collins, J.G.; Keene, F.R. Mechanism of cytotoxicity and cellular uptake of lipophilic inert dinuclear polypyridylruthenium(II) complexes. ChemMedChem, 2011, 6(5), 848-858.
[47]
Pierroz, V.; Joshi, T.; Leonidova, A.; Mari, C.; Schur, J.; Ott, I.; Spiccia, L.; Ferrari, S.; Gasser, G. Molecular and cellular characterization of the biological effects of ruthenium(II) complexes incorporating 2-pyridyl-2-pyrimidine-4-carboxylic acid. J. Am. Chem. Soc., 2012, 134(50), 20376-20387.
[48]
Joshi, T.; Pierroz, V.; Ferrari, S.; Gasser, G. Bis(dipyridophenazine)(2-(2′-pyridyl)pyrimidine-4-carboxylic acid)ruthenium(II) hexafluorophosphate: a lesson in stubbornness. ChemMedChem, 2014, 9(7), 1419-1427.
[49]
Wang, J-Q.; Zhang, P-Y.; Qian, C.; Hou, X-J.; Ji, L-N.; Chao, H. Mitochondria are the primary target in the induction of apoptosis by chiral ruthenium(II) polypyridyl complexes in cancer cells. J. Biol. Inorg. Chem., 2014, 19(3), 335-348.
[50]
Zeng, L.; Chen, Y.; Liu, J.; Huang, H.; Guan, R.; Ji, L.; Chao, H. Ruthenium(II) complexes with 2-phenylimidazo[4,5-f][1,10] phenanthroline derivatives that strongly combat cisplatin-resistant tumor cells. Sci. Rep., 2016, 6, 19449.
[51]
Du, Y.; Fu, X.; Li, H.; Chen, B.; Guo, Y.; Su, G.; Zhang, H.; Ning, F.; Lin, Y.; Mei, W.; Chen, T. Mitochondrial fragmentation is an important cellular event induced by ruthenium(II) polypyridyl complexes in osteosarcoma cells. ChemMedChem, 2014, 9(4), 714-718.
[52]
Liu, J.; Chen, Y.; Li, G.; Zhang, P.; Jin, C.; Zeng, L.; Ji, L.; Chao, H. Ruthenium(II) polypyridyl complexes as mitochondria-targeted two-photon photodynamic anticancer agents. Biomaterials, 2015, 56, 140-153.
[53]
Wilson, B.C.; Olivo, M.; Singh, G. Subcellular localization of Photofrin and aminolevulinic acid and photodynamic cross-resistance in vitro in radiation-induced fibrosarcoma cells sensitive or resistant to photofrin-mediated photodynamic therapy. Photochem. Photobiol., 1997, 65(1), 166-176.
[54]
Ke, H.; Wang, H.; Wong, W-K.; Mak, N-K.; Kwong, D.W.J.; Wong, K-L.; Tam, H-L. Responsive and mitochondria-specific ruthenium(II) complex for dual in vitro applications: two-photon (near-infrared) induced imaging and regioselective cell killing. Chem. Commun. (Camb.), 2010, 46(36), 6678-6680.
[55]
Zeng, L.; Chen, Y.; Huang, H.; Wang, J.; Zhao, D.; Ji, L.; Chao, H. Cyclometalated ruthenium(II) anthraquinone complexes exhibit strong anticancer activity in hypoxic tumor cells. Chemistry, 2015, 21(43), 15308-15319.
[56]
Sarkar, T.; Banerjee, S.; Hussain, A. Remarkable visible light-triggered cytotoxicity of mitochondria targeting mixed-ligand cobalt(III) complexes of curcumin and phenanthroline bases binding to human serum albumin. RSC Advances, 2015, 5, 16641-16653.
[57]
Fernandez-Moreira, V.; Marzo, I.; Gimeno, M.C. Luminescent Re(I) and Re(I)/Au(I) complexes as cooperative partners in cell imaging and cancer therapy. Chem. Sci. (Camb.), 2014, 5, 4434-4446.
[58]
Zhang, K.Y.; Tso, K.K-S.; Louie, M-W.; Liu, H-W.; Lo, K.K-W. A phosphorescent rhenium(I) tricarbonyl polypyridine complex appended with a fructose pendant that exhibits photocytotoxicity and enhanced uptake by breast cancer cells. Organometallics, 2013, 32, 5098-5102.
[59]
Ye, R-R.; Tan, C-P.; Lin, Y-N.; Ji, L-N.; Mao, Z-W. A phosphorescent rhenium(I) histone deacetylase inhibitor: mitochondrial targeting and paraptosis induction. Chem. Commun. (Camb.), 2015, 51(39), 8353-8356.
[60]
Imstepf, S.; Pierroz, V.; Rubbiani, R.; Felber, M.; Fox, T.; Gasser, G.; Alberto, R. Organometallic rhenium complexes divert doxorubicin to the mitochondria. Angew. Chem. Int. Ed. Engl., 2016, 55(8), 2792-2795.
[61]
Guo, Z.; Tong, W-L.; Chan, M.C.W. Luminescent oligo(ethylene glycol)-functionalized cyclometalated platinum(II) complexes: cellular characterization and mitochondria-specific localization. Chem. Commun. (Camb.), 2014, 50(14), 1711-1714.
[62]
Tso, K.K-S.; Leung, K-K.; Liu, H-W.; Lo, K.K-W. Photoactivatable cytotoxic agents derived from mitochondria-targeting luminescent iridium(III) poly(ethylene glycol) complexes modified with a nitrobenzyl linkage. Chem. Commun. (Camb.), 2016, 52(24), 4557-4560.
[63]
Cao, J-J.; Tan, C-P.; Chen, M-H.; Wu, N.; Yao, D-Y.; Liu, X-G.; Ji, L-N.; Mao, Z-W. Targeting cancer cell metabolism with mitochondria-immobilized phosphorescent cyclometalated iridium(iii) complexes. Chem. Sci. (Camb.), 2017, 8(1), 631-640.
[64]
Gupta, G.; Kumar, J.M.; Garci, A.; Nagesh, N.; Therrien, B. Exploiting natural products to build metalla-assemblies: the anticancer activity of embelin-derived Rh(III) and Ir(III) metalla-rectangles. Molecules, 2014, 19(5), 6031-6046.
[65]
Gupta, G.; Kumar, J.M.; Garci, A.; Rangaraj, N.; Nagesh, N.; Therrien, B. Anticancer activity of half-sandwich RhIII and IrIII metalla-prisms containing lipophilic side chains. ChemPlusChem, 2014, 79, 610-618.
[66]
Lemasters, J.J.; Ramshesh, V.K. Imaging of mitochondrial polarization and depolarization with cationic fluorophores. Methods Cell Biol., 2007, 80, 283-295.
[67]
Hynes, J.; Marroquin, L.D.; Ogurtsov, V.I.; Christiansen, K.N.; Stevens, G.J.; Papkovsky, D.B.; Will, Y. Investigation of drug-induced mitochondrial toxicity using fluorescence-based oxygen-sensitive probes. Toxicol. Sci., 2006, 92(1), 186-200.
[68]
Qiu-Yun, C.; Dong-Fang, Z.; Juan, H.; Wen-Jie, G.; Jing, G. Synthesis, anticancer activities, interaction with DNA and mitochondria of manganese complexes. J. Inorg. Biochem., 2010, 104(11), 1141-1147.
[69]
Xie, Q.; Liu, S.; Li, X.; Wu, Q.; Luo, Z.; Fu, X.; Cao, W.; Lan, G.; Li, D.; Zheng, W.; Chen, T. Dinuclear zinc(II) complexes containing (benzimidazol-2-yl)benzene that overcome drug resistance in hepatocellular carcinoma cells through induction of mitochondria fragmentation. Dalton Trans., 2014, 43(19), 6973-6976.
[70]
Li, S.; Zhang, S.; Jin, X.; Tan, X.; Lou, J.; Zhang, X.; Zhao, Y. Singly protonated dehydronorcantharidin silver coordination polymer induces apoptosis of lung cancer cells via reactive oxygen species-mediated mitochondrial pathway. Eur. J. Med. Chem., 2014, 86, 1-11.
[71]
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.
[72]
Liu, Z.; Romero-Canelón, I.; Habtemariam, A.; Clarkson, G.J.; Sadler, P.J. Potent half-sandwich iridium(III) anticancer complexes containing C^N-chelated and pyridine ligands. Organometallics, 2014, 33(19), 5324-5333.
[73]
Li, K.; Zou, T.; Chen, Y.; Guan, X.; Che, C-M. Pincer-type platinum(II) complexes containing N-heterocyclic carbene (NHC) ligand: Structures, photophysical and anion-binding properties, and anticancer activities. Chemistry, 2015, 21(20), 7441-7453.
[74]
Chen, T.; Mei, W-J.; Wong, Y-S.; Liu, J.; Liu, Y.; Xie, H-S.; Zheng, W-J. Chiral ruthenium polypyridyl complexes as mitochondria-targeted apoptosis inducers. MedChemComm, 2010, 1, 73-75.
[75]
Chen, T.; Liu, Y.; Zheng, W-J.; Liu, J.; Wong, Y-S. Ruthenium polypyridyl complexes that induce mitochondria-mediated apoptosis in cancer cells. Inorg. Chem., 2010, 49(14), 6366-6368.
[76]
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.
[77]
Mulcahy, S.P.; Gründler, K.; Frias, C.; Wagner, L.; Prokop, A.; Meggers, E. Discovery of a strongly apoptotic ruthenium complex through combinatorial coordination chemistry. Dalton Trans., 2010, 39(35), 8177-8182.
[78]
Chen, Y.; Qin, M-Y.; Wang, L.; Chao, H.; Ji, L-N.; Xu, A-L. A ruthenium(II) β-carboline complex induced p53-mediated apoptosis in cancer cells. Biochimie, 2013, 95(11), 2050-2059.
[79]
Zhao, Z.; Luo, Z.; Wu, Q.; Zheng, W.; Feng, Y.; Chen, T. Mixed-ligand ruthenium polypyridyl complexes as apoptosis inducers in cancer cells, the cellular translocation and the important role of ROS-mediated signaling. Dalton Trans., 2014, 43(45), 17017-17028.
[80]
Li, W.; Jiang, G-B.; Yao, J-H.; Wang, X-Z.; Wang, J.; Han, B-J.; Xie, Y-Y.; Lin, G-J.; Huang, H-L.; Liu, Y-J. Ruthenium(II) complexes: DNA-binding, cytotoxicity, apoptosis, cellular localization, cell cycle arrest, reactive oxygen species, mitochondrial membrane potential and western blot analysis. J. Photochem. Photobiol. B, 2014, 140, 94-104.
[81]
Lai, S-H.; Li, W.; Yao, J-H.; Han, B-J.; Jiang, G-B.; Zhang, C.; Zeng, C-C.; Liu, Y-J. Protein binding and anticancer activity studies of ruthenium(II) polypyridyl complexes toward BEL-7402 cells. J. Photochem. Photobiol. B, 2016, 158, 39-48.
[82]
Zhang, C.; Han, B-J.; Zeng, C-C.; Lai, S-H.; Li, W.; Tang, B.; Wan, D.; Jiang, G.B.; Liu, Y.J. Synthesis, characterization, in vitro cytotoxicity and anticancer effects of ruthenium(II) complexes on BEL-7402 cells. J. Inorg. Biochem., 2016, 157, 62-72.
[83]
Li, W.; Han, B-J.; Yao, J-H.; Jiang, G-B.; Liu, Y-J. Cytotoxicity in vitro, cell migration and apoptotic mechanism studies induced by ruthenium(II) complexes. RSC Advances, 2015, 5, 24534-24543.
[84]
Jiang, G-B.; Zheng, X.; Yao, J-H.; Han, B-J.; Li, W.; Wang, J.; Huang, H-L.; Liu, Y-J. Ruthenium(II) polypyridyl complexes induce BEL-7402 cell apoptosis by ROS-mediated mitochondrial pathway. J. Inorg. Biochem., 2014, 141, 170-179.
[85]
Chen, L.M.; Peng, F.; Li, G.D.; Jie, X.M.; Cai, K.R.; Cai, C.; Zhong, Y.; Zeng, H.; Li, W.; Zhang, Z.; Chen, J.C. The studies on the cytotoxicity in vitro, cellular uptake, cell cycle arrest and apoptosis-inducing properties of ruthenium methylimidazole complex [Ru(MeIm)4(p-cpip)](2.). J. Inorg. Biochem., 2016, 156, 64-74.
[86]
Kalaivani, P.; Prabhakaran, R.; Poornima, P.; Huang, R.; Hornebecq, V.; Dallemer, F.; Padma, V.V.; Natarajan, K. Synthesis and structural characterization of new ruthenium(II) complexes and investigation of their antiproliferative and metastatic effect against human lung cancer (A549) cells. RSC Advances, 2013, 3, 20363-20378.
[87]
Qian, C.; Wang, J-Q.; Song, C-L.; Wang, L-L.; Ji, L-N.; Chao, H. The induction of mitochondria-mediated apoptosis in cancer cells by ruthenium(II) asymmetric complexes. Metallomics, 2013, 5(7), 844-854.
[88]
Circu, M.L.; Aw, T.Y. Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic. Biol. Med., 2010, 48(6), 749-762.
[89]
Li, L.; Wong, Y-S.; Chen, T.; Fan, C.; Zheng, W. Ruthenium complexes containing bis-benzimidazole derivatives as a new class of apoptosis inducers. Dalton Trans., 2012, 41(4), 1138-1141.
[90]
Tan, C.; Lai, S.; Wu, S.; Hu, S.; Zhou, L.; Chen, Y.; Wang, M.; Zhu, Y.; Lian, W.; Peng, W.; Ji, L.; Xu, A. Nuclear permeable ruthenium(II) β-carboline complexes induce autophagy to antagonize mitochondrial-mediated apoptosis. J. Med. Chem., 2010, 53(21), 7613-7624.
[91]
Tan, C.; Wu, S.; Lai, S.; Wang, M.; Chen, Y.; Zhou, L.; Zhu, Y.; Lian, W.; Peng, W.; Ji, L.; Xu, A. Synthesis, structures, cellular uptake and apoptosis-inducing properties of highly cytotoxic ruthenium-Norharman complexes. Dalton Trans., 2011, 40(34), 8611-8621.
[92]
Sarkar, T.; Banerjee, S.; Mukherjee, S.; Hussain, A. Mitochondrial selectivity and remarkable photocytotoxicity of a ferrocenyl neodymium(III) complex of terpyridine and curcumin in cancer cells. Dalton Trans., 2016, 45(15), 6424-6438.
[93]
Huang, H.; Zhang, P.; Yu, B.; Jin, C.; Ji, L.; Chao, H. Synthesis, characterization and biological evaluation of mixed-ligand ruthenium(II) complexes for photodynamic therapy. Dalton Trans., 2015, 44(39), 17335-17345.
[94]
Li, Y.; Tan, C-P.; Zhang, W.; He, L.; Ji, L-N.; Mao, Z-W. Phosphorescent iridium(III)-bis-N-heterocyclic carbene complexes as mitochondria-targeted theranostic and photodynamic anticancer agents. Biomaterials, 2015, 39, 95-104.
[95]
Ye, R-R.; Tan, C-P.; He, L.; Chen, M-H.; Ji, L-N.; Mao, Z-W. Cyclometalated Ir(III) complexes as targeted theranostic anticancer therapeutics: combining HDAC inhibition with photodynamic therapy. Chem. Commun. (Camb.), 2014, 50(75), 10945-10948.
[96]
Ye, R-R.; Tan, C-P.; Ji, L-N.; Mao, Z-W. Coumarin-appended phosphorescent cyclometalated iridium(iii) complexes as mitochondria-targeted theranostic anticancer agents. Dalton Trans., 2016, 45(33), 13042-13051.
[97]
Bhattacharyya, A.; Dixit, A.; Mitra, K.; Banerjee, S.; Karande, A.A.; Chakravarty, A.R. BODIPY appended copper(II) complexes of curcumin showing mitochondria targeted remarkable photocytotoxicity in visible light. MedChemComm, 2015, 6, 846-851.
[98]
Sun, T.; Guan, X.; Zheng, M.; Jing, X.; Xie, Z. Mitochondria-localized fluorescent BODIPY-platinum conjugate. ACS Med. Chem. Lett., 2015, 6(4), 430-433.
[99]
Banerjee, S.; Prasad, P.; Khan, I.; Hussain, A.; Kondaiah, P.; Chakravarty, A.R. Mitochondria targeting photocytotoxic oxidovanadium(IV) complexes of curcumin and (acridinyl)dipyridophenazine in visible light. Z. Anorg. Allg. Chem., 2014, 640, 1195-1204.
[100]
Prasad, P.; Khan, I.; Kondaiah, P.; Chakravarty, A.R. Mitochondria-targeting oxidovanadium(IV) complex as a near-IR light photocytotoxic agent. Chemistry, 2013, 19(51), 17445-17455.
[101]
Kitanovic, I.; Can, S.; Alborzinia, H.; Kitanovic, A.; Pierroz, V.; Leonidova, A.; Pinto, A.; Spingler, B.; Ferrari, S.; Molteni, R.; Steffen, A.; Metzler-Nolte, N.; Wölfl, S.; Gasser, G. A deadly organometallic luminescent probe: anticancer activity of a ReI bisquinoline complex. Chemistry, 2014, 20(9), 2496-2507.
[102]
Tomsik, P.; Muthna, D.; Rezacova, M.; Micuda, S.; Cmielova, J.; Hroch, M.; Endlicher, R.; Cervinkova, Z.; Rudolf, E.; Hann, S.; Stibal, D.; Therrien, B.; Süss-Fink, G. [(p-MeC6H4Pri)2Ru2(SC6H4-p-But)3]Cl (diruthenium-1), a dinuclear arene ruthenium compound with very high anticancer activity: An in vitro and in vivo study. J. Organomet. Chem., 2015, 782, 42-51.
[103]
Schimler, S.D.; Hall, D.J.; Debbert, S.L. Anticancer (hexacarbonyldicobalt)propargyl aryl ethers: synthesis, antiproliferative activity, apoptosis induction, and effect on cellular oxidative stress. J. Inorg. Biochem., 2013, 119, 28-37.
[104]
Slator, C.; Barron, N.; Howe, O.; Kellett, A. [Cu(o-phthalate)(phenanthroline)] exhibits unique superoxide-mediated NCI-60 chemotherapeutic action through genomic DNA damage and mitochondrial dysfunction. ACS Chem. Biol., 2016, 11(1), 159-171.
[105]
Marín-Hernández, A.; Gracia-Mora, I.; Ruiz-Ramírez, L.; Moreno-Sánchez, R. Toxic effects of copper-based antineoplastic drugs (Casiopeinas) on mitochondrial functions. Biochem. Pharmacol., 2003, 65(12), 1979-1989.
[106]
Dhar, S.; Lippard, S.J. Mitaplatin, a potent fusion of cisplatin and the orphan drug dichloroacetate. Proc. Natl. Acad. Sci. USA, 2009, 106(52), 22199-22204.
[107]
Suntharalingam, K.; Song, Y.; Lippard, S.J. Conjugation of vitamin E analog α-TOS to Pt(IV) complexes for dual-targeting anticancer therapy. Chem. Commun. (Camb.), 2014, 50(19), 2465-2468.
[108]
Stacpoole, P.W. The pharmacology of dichloroacetate. Metabolism, 1989, 38(11), 1124-1144.
[109]
Xue, X.; You, S.; Zhang, Q.; Wu, Y.; Zou, G.Z.; Wang, P.C.; Zhao, Y.L.; Xu, Y.; Jia, L.; Zhang, X.; Liang, X-J. Mitaplatin increases sensitivity of tumor cells to cisplatin by inducing mitochondrial dysfunction. Mol. Pharm., 2012, 9(3), 634-644.
[110]
Zajac, J.; Kostrhunova, H.; Novohradsky, V.; Vrana, O.; Raveendran, R.; Gibson, D.; Kasparkova, J.; Brabec, V. Potentiation of mitochondrial dysfunction in tumor cells by conjugates of metabolic modulator dichloroacetate with a Pt(IV) derivative of oxaliplatin. J. Inorg. Biochem., 2016, 156, 89-97.
[111]
Wexselblatt, E.; Raveendran, R.; Salameh, S.; Friedman-Ezra, A.; Yavin, E.; Gibson, D. On the stability of Pt(IV) pro-drugs with haloacetato ligands in the axial positions. Chemistry, 2015, 21(7), 3108-3114.
[112]
Shiau, C-W.; Huang, J-W.; Wang, D-S.; Weng, J-R.; Yang, C-C.; Lin, C-H.; Li, C.; Chen, C-S. α-Tocopheryl succinate induces apoptosis in prostate cancer cells in part through inhibition of Bcl-xL/Bcl-2 function. J. Biol. Chem., 2006, 281(17), 11819-11825.
[113]
Mallick, A.; More, P.; Ghosh, S.; Chippalkatti, R.; Chopade, B.A.; Lahiri, M.; Basu, S. Dual drug conjugated nanoparticle for simultaneous targeting of mitochondria and nucleus in cancer cells. ACS Appl. Mater. Interfaces, 2015, 7(14), 7584-7598.
[114]
Muscella, A.; Calabriso, N.; Fanizzi, F.P.; De Pascali, S.A.; Urso, L.; Ciccarese, A.; Migoni, D.; Marsigliante, S. [Pt(O,O′-acac)(γ-acac)(DMS)], a new Pt compound exerting fast cytotoxicity in MCF-7 breast cancer cells via the mitochondrial apoptotic pathway. Br. J. Pharmacol., 2008, 153(1), 34-49.
[115]
Dalla Via, L.; García-Argáez, A.N.; Adami, A.; Grancara, S.; Martinis, P.; Toninello, A.; Belli Dell’Amico, D.; Labella, L.; Samaritani, S. Synthesis, antiproliferative and mitochondrial impairment activities of bis-alkyl-amino transplatinum complexes. Bioorg. Med. Chem., 2013, 21(22), 6965-6972.
[116]
Dalla Via, L.; Santi, S.; Di Noto, V.; Venzo, A.; Agostinelli, E.; Calcabrini, A.; Condello, M.; Toninello, A. Platinum(II) chloride indenyl complexes: electrochemical and biological evaluation. J. Biol. Inorg. Chem., 2011, 16(5), 695-713.
[117]
Chen, J.; Stubbe, J. Bleomycins: towards better therapeutics. Nat. Rev. Cancer, 2005, 5, 102-112.
[118]
Yeung, M.; Hurren, R.; Nemr, C.; Wang, X.; Hershenfeld, S.; Gronda, M.; Liyanage, S.; Wu, Y.; Augustine, J.; Lee, E.A.; Spagnuolo, P.A.; Southall, N.; Chen, C.; Zheng, W.; Jeyaraju, D.V.; Minden, M.D.; Laposa, R.; Schimmer, A.D. Mitochondrial DNA damage by bleomycin induces AML cell death. Apoptosis, 2015, 20(6), 811-820.
[119]
Skrtić, M.; Sriskanthadevan, S.; Jhas, B.; Gebbia, M.; Wang, X.; Wang, Z.; Hurren, R.; Jitkova, Y.; Gronda, M.; Maclean, N.; Lai, C.K.; Eberhard, Y.; Bartoszko, J.; Spagnuolo, P.; Rutledge, A.C.; Datti, A.; Ketela, T.; Moffat, J.; Robinson, B.H.; Cameron, J.H.; Wrana, J.; Eaves, C.J.; Minden, M.D.; Wang, J.C.; Dick, J.E.; Humphries, K.; Nislow, C.; Giaever, G.; Schimmer, A.D. Inhibition of mitochondrial translation as a therapeutic strategy for human acute myeloid leukemia. Cancer Cell, 2011, 20(5), 674-688.
[120]
Lagadinou, E.D.; Sach, A.; Callahan, K.; Rossi, R.M.; Neering, S.J.; Minhajuddin, M.; Ashton, J.M.; Pei, S.; Grose, V.; O’Dwyer, K.M.; Liesveld, J.L.; Brookes, P.S.; Becker, M.W.; Jordan, C.T. BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells. Cell Stem Cell, 2013, 12(3), 329-341.
[121]
Arner, E.S.J.; Holmgren, A. Thioredoxin–thioredoxin reductase – a system that has come of age. Eur. J. Biochem., 2000, 267, 6102-6109.
[122]
Burke-Gaffney, A.; Callister, M.E.J.; Nakamura, H. Thioredoxin: friend or foe in human disease? Trends Pharmacol. Sci., 2005, 26(8), 398-404.
[123]
Gromer, S.; Urig, S.; Becker, K. The thioredoxin system--from science to clinic. Med. Res. Rev., 2004, 24(1), 40-89.
[124]
Nguyen, P.; Awwad, R.T.; Smart, D.D.K.; Spitz, D.R.; Gius, D. Thioredoxin reductase as a novel molecular target for cancer therapy. Cancer Lett., 2006, 236(2), 164-174.
[125]
Becker, K.; Gromer, S.; Schirmer, R.H.; Müller, S. Thioredoxin reductase as a pathophysiological factor and drug target. Eur. J. Biochem., 2000, 267(20), 6118-6125.
[126]
Bindoli, A.; Rigobello, M.P.; Scutari, G.; Gabbiani, C.; Casini, A.; Messori, L. Thioredoxin reductase: A target for gold compounds acting as potential anticancer drugs. Coord. Chem. Rev., 2009, 253, 1692-1707.
[127]
McKeage, M.J.; Maharaj, L.; Berners-Price, S.J. Mechanisms of cytotoxicity and antitumor activity of gold(I). Coord. Chem. Rev., 2002, 232, 127-135.
[128]
Shaw, C.F. III Gold-based therapeutic agents. Chem. Rev., 1999, 99(9), 2589-2600.
[129]
Mirabelli, C.K.; Johnson, R.K.; Hill, D.T.; Faucette, L.F.; Girard, G.R.; Kuo, G.Y.; Sung, C.M.; Crooke, S.T. Correlation of the in vitro cytotoxic and in vivo antitumor activities of gold(I) coordination complexes. J. Med. Chem., 1986, 29(2), 218-223.
[130]
Marzano, C.; Gandin, V.; Folda, A.; Scutari, G.; Bindoli, A.; Rigobello, M.P. Inhibition of thioredoxin reductase by auranofin induces apoptosis in cisplatin-resistant human ovarian cancer cells. Free Radic. Biol. Med., 2007, 42(6), 872-881.
[131]
Rigobello, M.P.; Scutari, G.; Boscolo, R.; Bindoli, A. Induction of mitochondrial permeability transition by auranofin, a gold(I)-phosphine derivative. Br. J. Pharmacol., 2002, 136(8), 1162-1168.
[132]
Cox, A.G.; Brown, K.K.; Arner, E.S.J.; Hampton, M.B. The thioredoxin reductase inhibitor auranofin triggers apoptosis through a Bax/Bak-dependent process that involves peroxiredoxin 3 oxidation. Biochem. Pharmacol., 2008, 76(9), 1097-1109.
[133]
Gamberi, T.; Fiaschi, T.; Modesti, A.; Massai, L.; Messori, L.; Balzi, M.; Magherini, F. Evidence that the antiproliferative effects of auranofin in Saccharomyces cerevisiae arise from inhibition of mitochondrial respiration. Int. J. Biochem. Cell Biol., 2015, 65, 61-71.
[134]
Bragadin, M.; Scutari, G.; Folda, A.; Bindoli, A.; Rigobello, M.P. Effect of metal complexes on thioredoxin reductase and the regulation of mitochondrial permeability conditions. Ann. N. Y. Acad. Sci., 2004, 1030, 348-354.
[135]
Rigobello, M.P.; Scutari, G.; Folda, A.; Bindoli, A. Mitochondrial thioredoxin reductase inhibition by gold(I) compounds and concurrent stimulation of permeability transition and release of cytochrome c. Biochem. Pharmacol., 2004, 67(4), 689-696.
[136]
Rigobello, M.P.; Messori, L.; Marcon, G.; Agostina Cinellu, M.; Bragadin, M.; Folda, A.; Scutari, G.; Bindoli, A. Gold complexes inhibit mitochondrial thioredoxin reductase: consequences on mitochondrial functions. J. Inorg. Biochem., 2004, 98(10), 1634-1641.
[137]
Vergara, E.; Casini, A.; Sorrentino, F.; Zava, O.; Cerrada, E.; Rigobello, M.P.; Bindoli, A.; Laguna, M.; Dyson, P.J. Anticancer therapeutics that target selenoenzymes: synthesis, characterization, in vitro cytotoxicity, and thioredoxin reductase inhibition of a series of gold(I) complexes containing hydrophilic phosphine ligands. ChemMedChem, 2010, 5(1), 96-102.
[138]
García-Moreno, E.; Tomás, A.; Atrián-Blasco, E.; Gascón, S.; Romanos, E.; Rodriguez-Yoldi, M.J.; Cerrada, E.; Laguna, M. In vitro and in vivo evaluation of organometallic gold(I) derivatives as anticancer agents. Dalton Trans., 2016, 45(6), 2462-2475.
[139]
Garcia-Moreno, E.; Gascon, E.; Rodriguez-Yoldi, M.J.; Cerrada, E.; Laguna, M. S-Propargylthiopyridine phosphane derivatives as anticancer agents: Characterization and antitumor activity. Organometallics, 2013, 32, 3710-3720.
[140]
García-Moreno, E.; Gascón, S.; García de Jalón, J.A.; Romanos, E.; Rodriguez-Yoldi, M.J.; Cerrada, E.; Laguna, M. In vivo anticancer activity, toxicology and histopathological studies of the thiolate gold(I) complex [Au(Spyrimidine)(PTA-CH2Ph)]Br. Anticancer. Agents Med. Chem., 2015, 15(6), 773-782.
[141]
Gutiérrez, A.; Gracia-Fleta, L.; Marzo, I.; Cativiela, C.; Laguna, A.; Gimeno, M.C. Gold(I) thiolates containing amino acid moieties. Cytotoxicity and structure-activity relationship studies. Dalton Trans., 2014, 43(45), 17054-17066.
[142]
Gandin, V.; Fernandes, A.P.; Rigobello, M.P.; Dani, B.; Sorrentino, F.; Tisato, F.; Björnstedt, M.; Bindoli, A.; Sturaro, A.; Rella, R.; Marzano, C. Cancer cell death induced by phosphine gold(I) compounds targeting thioredoxin reductase. Biochem. Pharmacol., 2010, 79(2), 90-101.
[143]
Ott, I.; Qian, X.; Xu, Y.; Vlecken, D.H.W.; Marques, I.J.; Kubutat, D.; Will, J.; Sheldrick, W.S.; Jesse, P.; Prokop, A.; Bagowski, C.P. A gold(I) phosphine complex containing a naphthalimide ligand functions as a TrxR inhibiting antiproliferative agent and angiogenesis inhibitor. J. Med. Chem., 2009, 52(3), 763-770.
[144]
Meyer, A.; Bagowski, C.P.; Kokoschka, M.; Stefanopoulou, M.; Alborzinia, H.; Can, S.; Vlecken, D.H.; Sheldrick, W.S.; Wölfl, S.; Ott, I. On the biological properties of alkynyl phosphine gold(I) complexes. Angew. Chem. Int. Ed. Engl., 2012, 51(35), 8895-8899.
[145]
Hikisz, P.; Szczupak, Ł.; Koceva-Chyła, A.; Gu Spiel, A.; Oehninger, L.; Ott, I.; Therrien, B.; Solecka, J.; Kowalski, K. Anticancer and antibacterial activity studies of gold(I)-alkynyl chromones. Molecules, 2015, 20(11), 19699-19718.
[146]
Hoke, G.D.; Rush, G.F.; Bossard, G.F.; McArdle, J.V.; Jensen, B.D.; Mirabelli, C.K. Mechanism of alterations in isolated rat liver mitochondrial function induced by gold complexes of bidentate phosphines. J. Biol. Chem., 1988, 263(23), 11203-11210.
[147]
Rush, G.F.; Alberts, D.W.; Meunier, P.; Leffler, K.; Smith, P.F. In vivo and in vitro hepatotoxicity of a novel antineoplastic agent SKF101772 in male beagle dogs. Toxicologist, 1987, 7, 59-59.
[148]
McKeage, M.J.; Berners-Price, S.J.; Galettis, P.; Bowen, R.J.; Brouwer, W.; Ding, L.; Zhuang, L.; Baguley, B.C. Role of lipophilicity in determining cellular uptake and antitumour activity of gold phosphine complexes. Cancer Chemother. Pharmacol., 2000, 46(5), 343-350.
[149]
Wetzel, C.; Kunz, P.C.; Kassack, M.U.; Hamacher, A.; Böhler, P.; Watjen, W.; Ott, I.; Rubbiani, R.; Spingler, B. Gold(I) complexes of water-soluble diphos-type ligands: synthesis, anticancer activity, apoptosis and thioredoxin reductase inhibition. Dalton Trans., 2011, 40(36), 9212-9220.
[150]
Rackham, O.; Nichols, S.J.; Leedman, P.J.; Berners-Price, S.J.; Filipovska, A. A gold(I) phosphine complex selectively induces apoptosis in breast cancer cells: implications for anticancer therapeutics targeted to mitochondria. Biochem. Pharmacol., 2007, 74(7), 992-1002.
[151]
Caruso, F.; Pettinari, C.; Paduano, F.; Villa, R.; Marchetti, F.; Monti, E.; Rossi, M. Chemical behavior and in vitro activity of mixed phosphine gold(I) compounds on melanoma cell lines. J. Med. Chem., 2008, 51(6), 1584-1591.
[152]
Caruso, F.; Rossi, M.; Tanski, J.; Pettinari, C.; Marchetti, F. Antitumor activity of the mixed phosphine gold species chlorotriphenylphosphine-1,3-bis(diphenylphosphino)propanegold(I). J. Med. Chem., 2003, 46(9), 1737-1742.
[153]
Caruso, F.; Villa, R.; Rossi, M.; Pettinari, C.; Paduano, F.; Pennati, M.; Daidone, M.G.; Zaffaroni, N. Mitochondria are primary targets in apoptosis induced by the mixed phosphine gold species chlorotriphenylphosphine-1,3-bis(diphenylphosphino)propanegold(I) in melanoma cell lines. Biochem. Pharmacol., 2007, 73(6), 773-781.
[154]
Lupidi, G.; Avenali, L.; Bramucci, M.; Quassinti, L.; Pettinari, R.; Khalife, H.K.; Gali-Muhtasib, H.; Marchetti, F.; Pettinari, C. Synthesis, properties, and antitumor effects of a new mixed phosphine gold(I) compound in human colon cancer cells. J. Inorg. Biochem., 2013, 124, 78-87.
[155]
Rubbiani, R.; Kitanovic, I.; Alborzinia, H.; Can, S.; Kitanovic, A.; Onambele, L.A.; Stefanopoulou, M.; Geldmacher, Y.; Sheldrick, W.S.; Wolber, G.; Prokop, A.; Wölfl, S.; Ott, I. Benzimidazol-2-ylidene gold(I) complexes are thioredoxin reductase inhibitors with multiple antitumor properties. J. Med. Chem., 2010, 53(24), 8608-8618.
[156]
Rubbiani, R.; Can, S.; Kitanovic, I.; Alborzinia, H.; Stefanopoulou, M.; Kokoschka, M.; Mönchgesang, S.; Sheldrick, W.S.; Wölfl, S.; Ott, I. Comparative in vitro evaluation of N-heterocyclic carbene gold(I) complexes of the benzimidazolylidene type. J. Med. Chem., 2011, 54(24), 8646-8657.
[157]
Cheng, X.; Holenya, P.; Can, S.; Alborzinia, H.; Rubbiani, R.; Ott, I.; Wölfl, S. A TrxR inhibiting gold(I) NHC complex induces apoptosis through ASK1-p38-MAPK signaling in pancreatic cancer cells. Mol. Cancer, 2014, 13, 221.
[158]
Rubbiani, R.; Salassa, L.; de Almeida, A.; Casini, A.; Ott, I. Cytotoxic gold(I) N-heterocyclic carbene complexes with phosphane ligands as potent enzyme inhibitors. ChemMedChem, 2014, 9(6), 1205-1210.
[159]
Schuh, E.; Pflüger, C.; Citta, A.; Folda, A.; Rigobello, M.P.; Bindoli, A.; Casini, A.; Mohr, F. Gold(I) carbene complexes causing thioredoxin 1 and thioredoxin 2 oxidation as potential anticancer agents. J. Med. Chem., 2012, 55(11), 5518-5528.
[160]
Baker, M.V.; Barnard, P.J.; Berners-Price, S.J.; Brayshaw, S.K.; Hickey, J.L.; Skelton, B.W.; White, A.H. Cationic, linear Au(I) N-heterocyclic carbene complexes: synthesis, structure and anti-mitochondrial activity. Dalton Trans., 2006, (30), 3708-3715.
[161]
Hickey, J.L.; Ruhayel, R.A.; Barnard, P.J.; Baker, M.V.; Berners-Price, S.J.; Filipovska, A. Mitochondria-targeted chemotherapeutics: the rational design of gold(I) N-heterocyclic carbene complexes that are selectively toxic to cancer cells and target protein selenols in preference to thiols. J. Am. Chem. Soc., 2008, 130(38), 12570-12571.
[162]
Yan, K.; Lok, C-N.; Bierla, K.; Che, C-M. Gold(I) complex of N,N′-disubstituted cyclic thiourea with in vitro and in vivo anticancer properties-potent tight-binding inhibition of thioredoxin reductase. Chem. Commun. (Camb.), 2010, 46(41), 7691-7693.
[163]
Nandy, A.; Dey, S.K.; Das, S.; Munda, R.N.; Dinda, J.; Saha, K.D. Gold (I) N-heterocyclic carbene complex inhibits mouse melanoma growth by p53 upregulation. Mol. Cancer, 2014, 13, 57.
[164]
Muenzner, J.K.; Biersack, B.; Albrecht, A.; Rehm, T.; Lacher, U.; Milius, W.; Casini, A.; Zhang, J-J.; Ott, I.; Brabec, V.; Stuchlikova, O.; Andronache, I.C.; Kaps, L.; Schuppan, D.; Schobert, R. Ferrocenyl-coupled N-heterocyclic carbene complexes of gold(I): A successful approach to multinuclear anticancer drugs. Chemistry, 2016, 22(52), 18953-18962.
[165]
Bertrand, B.; de Almeida, A.; van der Burgt, E.P.M.; Picquet, M.; Citta, A.; Folda, A.; Rigobello, M.P.; Le Gendre, P.; Bodio, E.; Casini, A. New gold(I) organometallic compounds with biological activity in cancer cells. Eur. J. Inorg. Chem., 2014, 4532-4536.
[166]
Citta, A.; Schuh, E.; Mohr, F.; Folda, A.; Massimino, M.L.; Bindoli, A.; Casini, A.; Rigobello, M.P. Fluorescent silver(I) and gold(I)-N-heterocyclic carbene complexes with cytotoxic properties: mechanistic insights. Metallomics, 2013, 5(8), 1006-1015.
[167]
Li, Y.; Liu, G-F.; Tan, C-P.; Ji, L-N.; Mao, Z-W. Antitumor properties and mechanisms of mitochondria-targeted Ag(I) and Au(I) complexes containing N-heterocyclic carbenes derived from cyclophanes. Metallomics, 2014, 6(8), 1460-1468.
[168]
Barnard, P.J.; Baker, M.V.; Berners-Price, S.J.; Day, D.A. Mitochondrial permeability transition induced by dinuclear gold(I)-carbene complexes: potential new antimitochondrial antitumour agents. J. Inorg. Biochem., 2004, 98(10), 1642-1647.
[169]
Zou, T.; Lum, C.T.; Lok, C-N.; To, W-P.; Low, K-H.; Che, C-M. A binuclear gold(I) complex with mixed bridging diphosphine and bis(N-heterocyclic carbene) ligands shows favorable thiol reactivity and inhibits tumor growth and angiogenesis in vivo. Angew. Chem. Int. Ed. Engl., 2014, 53(23), 5810-5814.
[170]
Bertrand, B.; Citta, A.; Franken, I.L.; Picquet, M.; Folda, A.; Scalcon, V.; Rigobello, M.P.; Le Gendre, P.; Casini, A.; Bodio, E. Gold(I) NHC-based homo- and heterobimetallic complexes: synthesis, characterization and evaluation as potential anticancer agents. J. Biol. Inorg. Chem., 2015, 20(6), 1005-1020.
[171]
Coronnello, M.; Mini, E.; Caciagli, B.; Cinellu, M.A.; Bindoli, A.; Gabbiani, C.; Messori, L. Mechanisms of cytotoxicity of selected organogold(III) compounds. J. Med. Chem., 2005, 48(21), 6761-6765.
[172]
Che, C-M.; Sun, R.W-Y.; Yu, W-Y.; Ko, C-B.; Zhu, N.; Sun, H. Gold(III) porphyrins as a new class of anticancer drugs: cytotoxicity, DNA binding and induction of apoptosis in human cervix epitheloid cancer cells. Chem. Commun. (Camb.), 2003, (14), 1718-1719.
[173]
Ronconi, L.; Giovagnini, L.; Marzano, C.; Bettìo, F.; Graziani, R.; Pilloni, G.; Fregona, D. Gold dithiocarbamate derivatives as potential antineoplastic agents: design, spectroscopic properties, and in vitro antitumor activity. Inorg. Chem., 2005, 44(6), 1867-1881.
[174]
Messori, L.; Abbate, F.; Marcon, G.; Orioli, P.; Fontani, M.; Mini, E.; Mazzei, T.; Carotti, S.; O’Connell, T.; Zanello, P. Gold(III) complexes as potential antitumor agents: solution chemistry and cytotoxic properties of some selected gold(III) compounds. J. Med. Chem., 2000, 43(19), 3541-3548.
[175]
Zou, T.; Lum, C.T.; Chui, S.S-Y.; Che, C-M. Gold(III) complexes containing N-heterocyclic carbene ligands: thiol “switch-on” fluorescent probes and anti-cancer agents. Angew. Chem. Int. Ed. Engl., 2013, 52(10), 2930-2933.
[176]
Sun, R.W-S.; Lok, C-N.; Fong, T.T-H.; Li, C.K-L.; Yang, Z.; Zou, T.; Siu, A.F-M.; Che, C-M. A dinuclear cyclometalated gold(III)-phosphine complex targeting thioredoxin reductase inhibits hepatocellular carcinoma in vivo. Chem. Sci. (Camb.), 2013, 4, 1979-1988.
[177]
Shaik, N.; Martínez, A.; Augustin, I.; Giovinazzo, H.; Varela-Ramírez, A.; Sanaú, M.; Aguilera, R.J.; Contel, M. Synthesis of apoptosis-inducing iminophosphorane organogold(III) complexes and study of their interactions with biomolecular targets. Inorg. Chem., 2009, 48(4), 1577-1587.
[178]
Vela, L.; Contel, M.; Palomera, L.; Azaceta, G.; Marzo, I. Iminophosphorane-organogold(III) complexes induce cell death through mitochondrial ROS production. J. Inorg. Biochem., 2011, 105(10), 1306-1313.
[179]
Sun, R.W-Y.; Li, C.K-L.; Ma, D-L.; Yan, J.J.; Lok, C-N.; Leung, C-H.; Zhu, N.; Che, C-M. Stable anticancer gold(III)-porphyrin complexes: effects of porphyrin structure. Chemistry, 2010, 16(10), 3097-3113.
[180]
He, L.; Chen, T.; You, Y.; Hu, H.; Zheng, W.; Kwong, W-L.; Zou, T.; Che, C-M. A cancer-targeted nanosystem for delivery of gold(III) complexes: enhanced selectivity and apoptosis-inducing efficacy of a gold(III) porphyrin complex. Angew. Chem. Int. Ed. Engl., 2014, 53(46), 12532-12536.
[181]
Hu, D.; Liu, Y.; Lai, Y-T.; Tong, K-C.; Fung, Y-M.; Lok, C-N.; Che, C-M. Anticancer gold(III) porphyrins target mitochondrial chaperone Hsp60. Angew. Chem. Int. Ed. Engl., 2016, 55(4), 1387-1391.
[182]
Wang, Y.; He, Q.Y.; Che, C-M.; Chiu, J.F. Proteomic characterization of the cytotoxic mechanism of gold (III) porphyrin 1a, a potential anticancer drug. Proteomics, 2006, 6(1), 131-142.
[183]
Wang, Y.; He, Q.Y.; Sun, R.W.; Che, C-M.; Chiu, J.F. Cellular pharmacological properties of gold(III) porphyrin 1a, a potential anticancer drug lead. Eur. J. Pharmacol., 2007, 554(2-3), 113-122.
[184]
Wang, Y.; He, Q.Y.; Che, C-M.; Tsao, S.W.; Sun, R.W.; Chiu, J.F. Modulation of gold(III) porphyrin 1a-induced apoptosis by mitogen-activated protein kinase signaling pathways. Biochem. Pharmacol., 2008, 75(6), 1282-1291.
[185]
Li, W.; Xie, Y.; Sun, R.W.; Liu, Q.; Young, J.; Yu, W.Y.; Che, C-M.; Tam, P.K.; Ren, Y. Inhibition of Akt sensitises neuroblastoma cells to gold(III) porphyrin 1a, a novel antitumour drug induced apoptosis and growth inhibition. Br. J. Cancer, 2009, 101(2), 342-349.
[186]
Wang, Y.; He, Q-Y.; Sun, R.W-Y.; Che, C-M.; Chiu, J-F. GoldIII porphyrin 1a induced apoptosis by mitochondrial death pathways related to reactive oxygen species. Cancer Res., 2005, 65(24), 11553-11564.
[187]
Zeilstra-Ryalls, J.; Fayet, O.; Georgopoulos, C. The universally conserved GroE (Hsp60) chaperonins. Annu. Rev. Microbiol., 1991, 45, 301-325.
[188]
Nisemblat, S.; Yaniv, O.; Parnas, A.; Frolow, F.; Azem, A. Crystal structure of the human mitochondrial chaperonin symmetrical football complex. Proc. Natl. Acad. Sci. USA, 2015, 112(19), 6044-6049.
[189]
Cappello, F.; Gammazza, A.M.; Piccionello, A.P.; Campanella, C.; Pace, A.; de Marcario, E.C.; Marcario, A.J.L. Hsp60 chaperonopathies and chaperonotherapy: targets and agents. Expert Opin. Ther. Targets, 2014, 18, 185-208.
[190]
Desgrosellier, J.S.; Cheresh, D.A. Integrins in cancer: biological implications and therapeutic opportunities. Nat. Rev. Cancer, 2010, 10(1), 9-22.
[191]
Lum, C.T.; Wong, A.S-T.; Lin, M.C.M.; Che, C-M.; Sun, R.W-Y. A gold(III) porphyrin complex as an anti-cancer candidate to inhibit growth of cancer-stem cells. Chem. Commun. (Camb.), 2013, 49(39), 4364-4366.
[192]
Lum, C.T.; Sun, R.W-Y.; Zou, T.; Che, C-M. Gold(III) complexes inhibit growth of cisplatin-resistant ovarian cancer in association with upregulation of proapoptotic PMS2 gene. Chem. Sci. (Camb.), 2014, 5, 1579-1584.
[193]
Magherini, F.; Modesti, A.; Bini, L.; Puglia, M.; Landini, I.; Nobili, S.; Mini, E.; Cinellu, M.A.; Gabbiani, C.; Messori, L. Exploring the biochemical mechanisms of cytotoxic gold compounds: a proteomic study. J. Biol. Inorg. Chem., 2010, 15(4), 573-582.
[194]
Gamberi, T.; Massai, L.; Magherini, F.; Landini, I.; Fiaschi, T.; Scaletti, F.; Gabbiani, C.; Bianchi, L.; Bini, L.; Nobili, S.; Perrone, G.; Mini, E.; Messori, L.; Modesti, A. Proteomic analysis of A2780/S ovarian cancer cell response to the cytotoxic organogold(III) compound Aubipy(c). J. Proteomics, 2014, 103, 103-120.
[195]
Rigobello, M.P.; Messori, L.; Marcon, G.; Agostina Cinellu, M.; Bragadin, M.; Folda, A.; Scutari, G.; Bindoli, A. Gold complexes inhibit mitochondrial thioredoxin reductase: consequences on mitochondrial functions. J. Inorg. Biochem., 2004, 98(10), 1634-1641.
[196]
Casini, A.; Hartinger, C.; Gabbiani, C.; Mini, E.; Dyson, P.J.; Keppler, B.K.; Messori, L. Gold(III) compounds as anticancer agents: relevance of gold-protein interactions for their mechanism of action. J. Inorg. Biochem., 2008, 102(3), 564-575.
[197]
Saggioro, D.; Rigobello, M.P.; Paloschi, L.; Folda, A.; Moggach, S.A.; Parsons, S.; Ronconi, L.; Fregona, D.; Bindoli, A. Gold(III)-dithiocarbamato complexes induce cancer cell death triggered by thioredoxin redox system inhibition and activation of ERK pathway. Chem. Biol., 2007, 14(10), 1128-1139.
[198]
Chiara, F.; Gambalunga, A.; Sciacovelli, M.; Nicolli, A.; Ronconi, L.; Fregona, D.; Bernardi, P.; Rasola, A.; Trevisan, A. Chemotherapeutic induction of mitochondrial oxidative stress activates GSK-3α/β and Bax, leading to permeability transition pore opening and tumor cell death. Cell Death Dis., 2012, 3-444.
[199]
Nardon, C.; Chiara, F.; Brustolin, L.; Gambalunga, A.; Ciscato, F.; Rasola, A.; Trevisan, A.; Fregona, D. Gold(III)-pyrrolidinedithiocarbamato derivatives as antineoplastic agents. ChemistryOpen, 2015, 4(2), 183-191.
[200]
Cattaruzza, L.; Fregona, D.; Mongiat, M.; Ronconi, L.; Fassina, A.; Colombatti, A.; Aldinucci, D. Antitumor activity of gold(III)-dithiocarbamato derivatives on prostate cancer cells and xenografts. Int. J. Cancer, 2011, 128(1), 206-215.
[201]
Marzano, C.; Ronconi, L.; Chiara, F.; Giron, M.C.; Faustinelli, I.; Cristofori, P.; Trevisan, A.; Fregona, D. Gold(III)-dithiocarbamato anticancer agents: activity, toxicology and histopathological studies in rodents. Int. J. Cancer, 2011, 129(2), 487-496.
[202]
Nardon, C.; Schmitt, S.M.; Yang, H.; Zuo, J.; Fregona, D.; Dou, Q.P. Gold(III)-dithiocarbamato peptidomimetics in the forefront of the targeted anticancer therapy: preclinical studies against human breast neoplasia. PLoS One, 2014, 9(1), e84248.
[203]
Celegato, M.; Fregona, D.; Mongiat, M.; Ronconi, L.; Borghese, C.; Canzonieri, V.; Casagrande, N.; Nardon, C.; Colombatti, A.; Aldinucci, D. Preclinical activity of multiple-target gold(III)-dithiocarbamato peptidomimetics in prostate cancer cells and xenografts. Future Med. Chem., 2014, 6(11), 1249-1263.
[204]
Pratesi, A.; Gabbiani, C.; Ginanneschi, M.; Messori, L. Reactions of medicinally relevant gold compounds with the C-terminal motif of thioredoxin reductase elucidated by MS analysis. Chem. Commun. (Camb.), 2010, 46(37), 7001-7003.
[205]
Pratesi, A.; Gabbiani, C.; Michelucci, E.; Ginanneschi, M.; Papini, A.M.; Rubbiani, R.; Ott, I.; Messori, L. Insights on the mechanism of thioredoxin reductase inhibition by gold N-heterocyclic carbene compounds using the synthetic linear selenocysteine containing C-terminal peptide hTrxR(488-499): an ESI-MS investigation. J. Inorg. Biochem., 2014, 136, 161-169.
[206]
Gabbiani, C.; Mastrobuoni, G.; Sorrentino, F.; Dani, B.; Rigobello, M.P.; Bindoli, A.; Cinellu, M.A.; Pieraccini, G.; Messori, L.; Casini, A. Thioredoxin reductase, an emerging target for anticancer metallodrugs. Enzyme inhibition by cytotoxic gold(III) compounds studied with combined mass spectrometry and biochemical assays. MedChemComm, 2011, 2, 50-54.
[207]
Fritz-Wolf, K.; Urig, S.; Becker, K. The structure of human thioredoxin reductase 1 provides insights into C-terminal rearrangements during catalysis. J. Mol. Biol., 2007, 370(1), 116-127.
[208]
Lum, C.T.; Yang, Z.F.; Li, H.Y.; Wai-Yin, Sun R.; Fan, S.T.; Poon, R.T.P.; Lin, M.C.M.; Che, C-M.; Kung, H.F. Gold(III) compound is a novel chemocytotoxic agent for hepatocellular carcinoma. Int. J. Cancer, 2006, 118(6), 1527-1538.
[209]
Karver, M.R.; Krishnamurthy, D.; Kulkarni, R.A.; Bottini, N.; Barrios, A.M. Identifying potent, selective protein tyrosine phosphatase inhibitors from a library of Au(I) complexes. J. Med. Chem., 2009, 52(21), 6912-6918.
[210]
Wang, Q.; Janzen, N.; Ramachandran, C.; Jirik, F. Mechanism of inhibition of protein-tyrosine phosphatases by disodium aurothiomalate. Biochem. Pharmacol., 1997, 54(6), 703-711.
[211]
Weidauer, E.; Yasuda, Y.; Biswal, B.K.; Cherny, M.; James, M.N.G.; Brömme, D. Effects of disease-modifying anti-rheumatic drugs (DMARDs) on the activities of rheumatoid arthritis-associated cathepsins K and S. Biol. Chem., 2007, 388(3), 331-336.
[212]
Chircorian, A.; Barrios, A.M. Inhibition of lysosomal cysteine proteases by chrysotherapeutic compounds: a possible mechanism for the antiarthritic activity of Au(I). Bioorg. Med. Chem. Lett., 2004, 14(20), 5113-5116.
[213]
Oehninger, L.; Stefanopoulou, M.; Alborzinia, H.; Schur, J.; Ludewig, S.; Namikawa, K.; Muñoz-Castro, A.; Köster, R.W.; Baumann, K.; Wölfl, S.; Sheldrick, W.S.; Ott, I. Evaluation of arene ruthenium(II) N-heterocyclic carbene complexes as organometallics interacting with thiol and selenol containing biomolecules. Dalton Trans., 2013, 42(5), 1657-1666.
[214]
Casini, A.; Gabbiani, C.; Sorrentino, F.; Rigobello, M.P.; Bindoli, A.; Geldbach, T.J.; Marrone, A.; Re, N.; Hartinger, C.G.; Dyson, P.J.; Messori, L. Emerging protein targets for anticancer metallodrugs: inhibition of thioredoxin reductase and cathepsin B by antitumor ruthenium(II)-arene compounds. J. Med. Chem., 2008, 51(21), 6773-6781.
[215]
Mura, P.; Camalli, M.; Bindoli, A.; Sorrentino, F.; Casini, A.; Gabbiani, C.; Corsini, M.; Zanello, P.; Rigobello, M.P.; Messori, L. Activity of rat cytosolic thioredoxin reductase is strongly decreased by trans-[bis(2-amino-5- methylthiazole)tetrachlororuthenate(III)]: first report of relevant thioredoxin reductase inhibition for a ruthenium compound. J. Med. Chem., 2007, 50(24), 5871-5874.
[216]
Luo, Z.; Yu, L.; Yang, F.; Zhao, Z.; Yu, B.; Lai, H.; Wong, K-H.; Ngai, S-M.; Zheng, W.; Chen, T. Ruthenium polypyridyl complexes as inducer of ROS-mediated apoptosis in cancer cells by targeting thioredoxin reductase. Metallomics, 2014, 6(8), 1480-1490.
[217]
Lu, J.; Chew, E.H.; Holmgren, A. Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide. Proc. Natl. Acad. Sci. USA, 2007, 104(30), 12288-12293.
[218]
Gatliff, J.; East, D.; Crosby, J.; Abeti, R.; Harvey, R.; Craigen, W.; Parker, P.; Campanella, M. TSPO interacts with VDAC1 and triggers a ROS-mediated inhibition of mitochondrial quality control. Autophagy, 2014, 10(12), 2279-2296.
[219]
Scarf, A.M.; Ittner, L.M.; Kassiou, M. The translocator protein (18 kDa): central nervous system disease and drug design. J. Med. Chem., 2009, 52(3), 581-592.
[220]
Galiegue, S.; Tinel, N.; Casellas, P. The peripheral benzodiazepine receptor: a promising therapeutic drug target. Curr. Med. Chem., 2003, 10(16), 1563-1572.
[221]
Maaser, K.; Grabowski, P.; Sutter, A.P.; Höpfner, M.; Foss, H.D.; Stein, H.; Berger, G.; Gavish, M.; Zeitz, M.; Scherübl, H. Overexpression of the peripheral benzodiazepine receptor is a relevant prognostic factor in stage III colorectal cancer. Clin. Cancer Res., 2002, 8(10), 3205-3209.
[222]
Miettinen, H.; Kononen, J.; Haapasalo, H.; Helén, P.; Sallinen, P.; Harjuntausta, T.; Helin, H.; Alho, H. Expression of peripheral-type benzodiazepine receptor and diazepam binding inhibitor in human astrocytomas: relationship to cell proliferation. Cancer Res., 1995, 55(12), 2691-2695.
[223]
Veenman, L.; Levin, E.; Weisinger, G.; Leschiner, S.; Spanier, I.; Snyder, S.H.; Weizman, A.; Gavish, M. Peripheral-type benzodiazepine receptor density and in vitro tumorigenicity of glioma cell lines. Biochem. Pharmacol., 2004, 68(4), 689-698.
[224]
Decaudin, D.; Castedo, M.; Nemati, F.; Beurdeley-Thomas, A.; De Pinieux, G.; Caron, A.; Pouillart, P.; Wijdenes, J.; Rouillard, D.; Kroemer, G.; Poupon, M.F. Peripheral benzodiazepine receptor ligands reverse apoptosis resistance of cancer cells in vitro and in vivo. Cancer Res., 2002, 62(5), 1388-1393.
[225]
Oudard, S.; Miccoli, L.; Dutrillaux, B.; Poupon, M.F. [Targeting the gene of glucose metabolism for the treatment of advanced gliomas]. Bull. Cancer, 1998, 85(7), 622-626.
[226]
Cappelli, A.; Pericot Mohr, Gl.; Gallelli, A.; Giuliani, G.; Anzini, M.; Vomero, S.; Fresta, M.; Porcu, P.; Maciocco, E.; Concas, A.; Biggio, G.; Donati, A. Structure-activity relationships in carboxamide derivatives based on the targeted delivery of radionuclides and boron atoms by means of peripheral benzodiazepine receptor ligands. J. Med. Chem., 2003, 46(17), 3568-3571.
[227]
Guo Zw, Z.; Gallo, J.M. Selective protection of 2′,2′-difluorodeoxycytidine (gemcitabine). J. Org. Chem., 1999, 64(22), 8319-8322.
[228]
Guo, P.; Ma, J.; Li, S.; Guo, Z.; Adams, A.L.; Gallo, J.M. Targeted delivery of a peripheral benzodiazepine receptor ligand-gemcitabine conjugate to brain tumors in a xenograft model. Cancer Chemother. Pharmacol., 2001, 48(2), 169-176.
[229]
George, P.G.; Rossey, G.; Sevrin, M.; Arbilla, S.; Depoortere, H.; Wick, A. Alpidem: Synthesis, physicochemical properties and structure-activity relationships. Monograph Ser., 1993, 8, 49-59.
[230]
Enguehard-Gueiffier, C.; Gueiffier, A. Recent progress in the pharmacology of imidazo[1,2-a]pyridines. Mini Rev. Med. Chem., 2007, 7(9), 888-899.
[231]
Margiotta, N.; Ostuni, R.; Ranaldo, R.; Denora, N.; Laquintana, V.; Trapani, G.; Liso, G.; Natile, G. Synthesis and characterization of a platinum(II) complex tethered to a ligand of the peripheral benzodiazepine receptor. J. Med. Chem., 2007, 50(5), 1019-1027.
[232]
Margiotta, N.; Denora, N.; Ostuni, R.; Laquintana, V.; Anderson, A.; Johnson, S.W.; Trapani, G.; Natile, G. Platinum(II) complexes with bioactive carrier ligands having high affinity for the translocator protein. J. Med. Chem., 2010, 53(14), 5144-5154.
[233]
Bentzion, D.; Lipatov, O.; Polyakov, I.; MacKintosh, R.; Eckardt, J.; Breitz, H. 2007.
[234]
Savino, S.; Denora, N.; Iacobazzi, R.M.; Porcelli, L.; Azzariti, A.; Natile, G.; Margiotta, N. Synthesis, characterization, and cytotoxicity of the first oxaliplatin Pt(IV) derivative having a TSPO ligand in the axial position. Int. J. Mol. Sci., 2016, 17(7), 1010.
[235]
Margiotta, N.; Denora, N.; Piccinonna, S.; Laquintana, V.; Lasorsa, F.M.; Franco, M.; Natile, G. Synthesis, characterization, and in vitro evaluation of new coordination complexes of platinum(II) and rhenium(I) with a ligand targeting the translocator protein (TSPO). Dalton Trans., 2014, 43(43), 16252-16264.
[236]
Denora, N.; Margiotta, N.; Laquintana, V.; Lopedota, A.; Cutrignelli, A.; Losacco, M.; Franco, M.; Natile, G. Synthesis, characterization, and in vitro evaluation of a new TSPO-selective bifunctional chelate ligand. ACS Med. Chem. Lett., 2014, 5(6), 685-689.
[237]
Piccinonna, S.; Margiotta, N.; Denora, N.; Iacobazzi, R.M.; Pacifico, C.; Trapani, G.; Natile, G. A model radiopharmaceutical agent targeted to translocator protein 18 kDa (TSPO). Dalton Trans., 2013, 42(28), 10112-10115.
[238]
Piccinonna, S.; Denora, N.; Margiotta, N.; Laquintana, V.; Trapani, G.; Natile, G. Synthesis, characterization, and binding to the translocator protein (18 kDa, TSPO) of a new rhenium complex as a model of radiopharmaceutical agents. Z. Anorg. Allg. Chem., 2013, 639, 1606-1612.
[239]
Neuzil, J.; Dong, L-F.; Rohlena, J.; Truksa, J.; Ralph, S.J. Classification of mitocans, anti-cancer drugs acting on mitochondria. Mitochondrion, 2013, 13(3), 199-208.
[240]
Ralph, S.J.; Low, P.; Dong, L.; Lawen, A.; Neuzil, J. Mitocans: mitochondrial targeted anti-cancer drugs as improved therapies and related patent documents. Recent Patents Anticancer Drug Discov., 2006, 1(3), 327-346.
[241]
Panda, V.; Khambat, P.; Patil, S. Mitocans as novel agents for anticancer therapy: An overview. Int. J. Clin. Med., 2011, 2, 515-529.

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