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Novel Second-Generation Di-2-Pyridylketone Thiosemicarbazones Show Synergism with Standard Chemotherapeutics and Demonstrate Potent Activity against Lung Cancer Xenografts after Oral and Intravenous Administration in Vivo

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† Iron Metabolism and Chelation Program, Department of Pathology and Bosch Institute, University of Sydney, Sydney, New South Wales 2006, Australia
‡ School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland 4072, Australia
*Phone: +61-2-9036-6548. Fax: +61-2-9036-6549. E-mail: [email protected]
Cite this: J. Med. Chem. 2012, 55, 16, 7230–7244
Publication Date (Web):August 3, 2012
https://doi.org/10.1021/jm300768u
Copyright © 2012 American Chemical Society
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    Abstract

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    We developed a series of second-generation di-2-pyridyl ketone thiosemicarbazone (DpT) and 2-benzoylpyridine thiosemicarbazone (BpT) ligands to improve the efficacy and safety profile of these potential antitumor agents. Two novel DpT analogues, Dp4e4mT and DpC, exhibited pronounced and selective activity against human lung cancer xenografts in vivo via the intravenous and oral routes. Importantly, these analogues did not induce the cardiotoxicity observed at high nonoptimal doses of the first-generation DpT analogue, Dp44mT. The Cu(II) complexes of these ligands exhibited potent antiproliferative activity having redox potentials in a range accessible to biological reductants. The activity of the copper complexes of Dp4e4mT and DpC against lung cancer cells was synergistic in combination with gemcitabine or cisplatin. It was demonstrated by EPR spectroscopy that dimeric copper compounds of the type [CuLCl]2, identified crystallographically, dissociate in solution to give monomeric 1:1 Cu:ligand complexes. These monomers represent the biologically active form of the complex.

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    Body and organ weights, hematological indices from in vivo tumor xenograft experiments, experimental and simulated EPR spectra, and cyclic voltammetry of Cu complexes. This material is available free of charge via the Internet at http://pubs.acs.org.

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    67. Winaki P. Sohtun, Themmila Khamrang, Arunachalam Kannan, Gowdhami Balakrishnan, Dhandayutham Saravanan, Mohammad Abdulkader Akhbarsha, Marappan Velusamy, Mallayan Palaniandavar. Iron(III) bis‐complexes of Schiff bases of S ‐methyldithiocarbazates: Synthesis, structure, spectral and redox properties and cytotoxicity. Applied Organometallic Chemistry 2020, 34 (5) https://doi.org/10.1002/aoc.5593
    68. S. Krishan, S. Sahni, L.Y.W. Leck, P.J. Jansson, D.R. Richardson. Regulation of autophagy and apoptosis by Dp44mT-mediated activation of AMPK in pancreatic cancer cells. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2020, 1866 (5) , 165657. https://doi.org/10.1016/j.bbadis.2019.165657
    69. Raquel Alcaraz, Pilar Muñiz, Mónica Cavia, Óscar Palacios, Katia G. Samper, Rubén Gil-García, Alondra Jiménez-Pérez, Javier García-Tojal, Carlos García-Girón. Thiosemicarbazone-metal complexes exhibiting cytotoxicity in colon cancer cell lines through oxidative stress. Journal of Inorganic Biochemistry 2020, 206 , 110993. https://doi.org/10.1016/j.jinorgbio.2020.110993
    70. Sundus N. Maqbool, Syer C. Lim, Kyung Chan Park, Rumeza Hanif, Des R. Richardson, Patric J. Jansson, Zaklina Kovacevic. Overcoming tamoxifen resistance in oestrogen receptor‐positive breast cancer using the novel thiosemicarbazone anti‐cancer agent, DpC. British Journal of Pharmacology 2020, 177 (10) , 2365-2380. https://doi.org/10.1111/bph.14985
    71. Rikki A. M. Brown, Kirsty L. Richardson, Tasnuva D. Kabir, Debbie Trinder, Ruth Ganss, Peter J. Leedman. Altered Iron Metabolism and Impact in Cancer Biology, Metastasis, and Immunology. Frontiers in Oncology 2020, 10 https://doi.org/10.3389/fonc.2020.00476
    72. Alireza Habibi, Seyed Ataollah Sadat Shandiz, Ali salehzadeh, Zeinab Moradi-Shoeili. Novel pyridinecarboxaldehyde thiosemicarbazone conjugated magnetite nanoparticulates (MNPs) promote apoptosis in human lung cancer A549 cells. JBIC Journal of Biological Inorganic Chemistry 2020, 25 (1) , 13-22. https://doi.org/10.1007/s00775-019-01728-4
    73. Kyung Chan Park, Bekesho Geleta, Lionel Yi Wen Leck, Jasmina Paluncic, Shannon Chiang, Patric J. Jansson, Zaklina Kovacevic, Des R. Richardson. Thiosemicarbazones suppress expression of the c-Met oncogene by mechanisms involving lysosomal degradation and intracellular shedding. Journal of Biological Chemistry 2020, 295 (2) , 481-503. https://doi.org/10.1074/jbc.RA119.011341
    74. Tishauna L.C. Green, Peter N. Nelson, Mark A.W. Lawrence. Spectroscopic, optical sensing and RedOx behaviour of 1, 5-diphenylcarbazone. Journal of Molecular Structure 2019, 1195 , 426-434. https://doi.org/10.1016/j.molstruc.2019.06.011
    75. Mark A.W. Lawrence, Shannen C. Lorraine, Kerrie-Ann Wilson, Kirk Wilson. Review: Voltammetric properties and applications of hydrazones and azo moieties. Polyhedron 2019, 173 , 114111. https://doi.org/10.1016/j.poly.2019.114111
    76. Christopher J Parkinson, Geoffrey W Birrell, Marina Chavchich, Donna Mackenzie, Richard K Haynes, Carmen de Kock, Des R Richardson, Michael D Edstein. Development of pyridyl thiosemicarbazones as highly potent agents for the treatment of malaria after oral administration. Journal of Antimicrobial Chemotherapy 2019, 74 (10) , 2965-2973. https://doi.org/10.1093/jac/dkz290
    77. Sharleen V Menezes, Leyla Fouani, Michael L H Huang, Bekesho Geleta, Sanaz Maleki, Alexander Richardson, Des R Richardson, Zaklina Kovacevic. The metastasis suppressor, NDRG1, attenuates oncogenic TGF-β and NF-κB signaling to enhance membrane E-cadherin expression in pancreatic cancer cells. Carcinogenesis 2019, 40 (6) , 805-818. https://doi.org/10.1093/carcin/bgy178
    78. Sumit Sahni, Kyung Chan Park, Zaklina Kovacevic, Des R. Richardson. Two mechanisms involving the autophagic and proteasomal pathways process the metastasis suppressor protein, N-myc downstream regulated gene 1. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2019, 1865 (6) , 1361-1378. https://doi.org/10.1016/j.bbadis.2019.02.008
    79. Anna Mrozek-Wilczkiewicz, Katarzyna Malarz, Marta Rejmund, Jaroslaw Polanski, Robert Musiol. Anticancer activity of the thiosemicarbazones that are based on di-2-pyridine ketone and quinoline moiety. European Journal of Medicinal Chemistry 2019, 171 , 180-194. https://doi.org/10.1016/j.ejmech.2019.03.027
    80. Petra Reimerová, Ján Stariat, Hana Bavlovič Piskáčková, Hana Jansová, Jaroslav Roh, Danuta S. Kalinowski, Miloslav Macháček, Tomáš Šimůnek, Des R. Richardson, Petra Štěrbová-Kovaříková. Novel SPME fibers based on a plastic support for determination of plasma protein binding of thiosemicarbazone metal chelators: a case example of DpC, an anti-cancer drug that entered clinical trials. Analytical and Bioanalytical Chemistry 2019, 411 (11) , 2383-2394. https://doi.org/10.1007/s00216-019-01681-w
    81. Angelica M. Merlot, Danuta S. Kalinowski, Zaklina Kovacevic, Patric J. Jansson, Sumit Sahni, Michael L.-H. Huang, Darius J.R. Lane, Hiu Lok, Des R. Richardson. Exploiting Cancer Metal Metabolism using Anti-Cancer Metal- Binding Agents. Current Medicinal Chemistry 2019, 26 (2) , 302-322. https://doi.org/10.2174/0929867324666170705120809
    82. Hana Jansová, Tomáś Šimůnek. Cardioprotective Potential of Iron Chelators and Prochelators. Current Medicinal Chemistry 2019, 26 (2) , 288-301. https://doi.org/10.2174/0929867324666170920155439
    83. Leyla Fouani, Zaklina Kovacevic, Des R. Richardson. Targeting Oncogenic Nuclear Factor Kappa B Signaling with Redox-Active Agents for Cancer Treatment. Antioxidants & Redox Signaling 2019, 30 (8) , 1096-1123. https://doi.org/10.1089/ars.2017.7387
    84. Petra Heffeter, Veronika F.S. Pape, Éva A. Enyedy, Bernhard K. Keppler, Gergely Szakacs, Christian R. Kowol. Anticancer Thiosemicarbazones: Chemical Properties, Interaction with Iron Metabolism, and Resistance Development. Antioxidants & Redox Signaling 2019, 30 (8) , 1062-1082. https://doi.org/10.1089/ars.2017.7487
    85. Rayan S. Moussa, Kyung Chan Park, Zaklina Kovacevic, Des R. Richardson. Ironing out the role of the cyclin-dependent kinase inhibitor, p21 in cancer: Novel iron chelating agents to target p21 expression and activity. Free Radical Biology and Medicine 2019, 133 , 276-294. https://doi.org/10.1016/j.freeradbiomed.2018.03.027
    86. Sharleen V. Menezes, Zaklina Kovacevic, Des R. Richardson. The metastasis suppressor NDRG1 down-regulates the epidermal growth factor receptor via a lysosomal mechanism by up-regulating mitogen-inducible gene 6. Journal of Biological Chemistry 2019, 294 (11) , 4045-4064. https://doi.org/10.1074/jbc.RA118.006279
    87. Wanbao Cao, Jinxu Qi, Kun Qian, Liang Tian, Zhen Cheng, Yihong Wang. Structure−activity relationships of 2‑quinolinecarboxaldehyde thiosemicarbazone gallium(III) complexes with potent and selective anticancer activity. Journal of Inorganic Biochemistry 2019, 191 , 174-182. https://doi.org/10.1016/j.jinorgbio.2018.11.017
    88. Weiping Liu. Crystal structure of 2-(bis(4-fluorophenyl)methylene)hydrazine-1-carbothioamide, C 14 H 11 F 2 N 3 S. Zeitschrift für Kristallographie - New Crystal Structures 2018, 233 (6) , 1089-1090. https://doi.org/10.1515/ncrs-2018-0214
    89. Jinxu Qi, Qian Yao, Liang Tian, Yihong Wang. Piperidylthiosemicarbazones Cu(II) complexes with a high anticancer activity by catalyzing hydrogen peroxide to degrade DNA and promote apoptosis. European Journal of Medicinal Chemistry 2018, 158 , 853-862. https://doi.org/10.1016/j.ejmech.2018.09.034
    90. Kyung Chan Park, Sharleen V. Menezes, Danuta S. Kalinowski, Sumit Sahni, Patric J. Jansson, Zaklina Kovacevic, Des R. Richardson. Identification of differential phosphorylation and sub-cellular localization of the metastasis suppressor, NDRG1. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2018, 1864 (8) , 2644-2663. https://doi.org/10.1016/j.bbadis.2018.04.011
    91. Carmela Bonaccorso, Giulia Grasso, Nicolò Musso, Vincenza Barresi, Daniele F. Condorelli, Diego La Mendola, Enrico Rizzarelli. Water soluble glucose derivative of thiocarbohydrazone acts as ionophore with cytotoxic effects on tumor cells. Journal of Inorganic Biochemistry 2018, 182 , 92-102. https://doi.org/10.1016/j.jinorgbio.2018.01.019
    92. Marta Rejmund, Anna Mrozek-Wilczkiewicz, Katarzyna Malarz, Monika Pyrkosz-Bulska, Kamila Gajcy, Mieczyslaw Sajewicz, Robert Musiol, Jaroslaw Polanski, . Piperazinyl fragment improves anticancer activity of Triapine. PLOS ONE 2018, 13 (4) , e0188767. https://doi.org/10.1371/journal.pone.0188767
    93. Rayan S. Moussa, Zaklina Kovacevic, Dong-Hun Bae, Darius J.R. Lane, Des R. Richardson. Transcriptional regulation of the cyclin-dependent kinase inhibitor, p21 CIP1/WAF1 , by the chelator, Dp44mT. Biochimica et Biophysica Acta (BBA) - General Subjects 2018, 1862 (3) , 761-774. https://doi.org/10.1016/j.bbagen.2017.10.009
    94. E.A. Akam, R.D. Utterback, J.R. Marcero, H.A. Dailey, E. Tomat. Disulfide-masked iron prochelators: Effects on cell death, proliferation, and hemoglobin production. Journal of Inorganic Biochemistry 2018, 180 , 186-193. https://doi.org/10.1016/j.jinorgbio.2017.12.016
    95. Mark A.W. Lawrence, Kerry-Ann Green, Peter N. Nelson, Shannen C. Lorraine. Review: Pincer ligands—Tunable, versatile and applicable. Polyhedron 2018, 143 , 11-27. https://doi.org/10.1016/j.poly.2017.08.017
    96. Lina Al-Akra, Dong-Hun Bae, Sumit Sahni, Michael L.H. Huang, Kyung Chan Park, Darius J.R. Lane, Patric J. Jansson, Des R. Richardson. Tumor stressors induce two mechanisms of intracellular P-glycoprotein–mediated resistance that are overcome by lysosomal-targeted thiosemicarbazones. Journal of Biological Chemistry 2018, 293 (10) , 3562-3587. https://doi.org/10.1074/jbc.M116.772699
    97. Mohamad M.E. Shakdofa, Hanan A. Mousa, Ahmed M.A. Elseidy, Ammar A. Labib, Mamdouh M. Ali, Amira S. Abd‐El‐All. Anti‐proliferative activity of newly synthesized Cd(II), Cu(II), Zn(II),Ni(II), Co(II), VO(II), and Mn(II) complexes of 2‐((4,9‐dimethoxy‐5‐oxo‐5H‐furo[3,2‐g]chromen‐6‐yl)methylene) hydrazinecarbothioamide on three human cancer cells. Applied Organometallic Chemistry 2018, 32 (1) https://doi.org/10.1002/aoc.3936
    98. Yan Fang, Jie Li, Pei-Pei Han, Qiu-Xia Han, Ming-Xue Li. Less toxic zinc( ii ), diorganotin( iv ), gallium( iii ) and cadmium( ii ) complexes derived from 2-benzoylpyridine N , N -dimethylthiosemicarbazone: synthesis, crystal structures, cytotoxicity and investigations of mechanisms of action. Toxicology Research 2018, 7 (5) , 987-993. https://doi.org/10.1039/C8TX00127H
    99. Jinxu Qi, Yunyun Zheng, Kun Qian, Liang Tian, Guo-Xin Zhang, Zhen Cheng, Yihong Wang. Synthesis, crystal structure and antiproliferative mechanisms of 2-acetylpyridine-thiosemicarbazones Ga(III) with a greater selectivity against tumor cells. Journal of Inorganic Biochemistry 2017, 177 , 110-117. https://doi.org/10.1016/j.jinorgbio.2017.09.012
    100. Geraldine Graser-Loescher, Agnes Schoenhuber, Caroline Ciglenec, Sabine Eberl, Georg Krupitza, Robert M. Mader, Surender S. Jadav, Venkatesan Jayaprakash, Monika Fritzer-Szekeres, Thomas Szekeres, Philipp Saiko. Thiosemicarbazone derivatives, thiazolyl hydrazones, effectively inhibit leukemic tumor cell growth: Down-regulation of ribonucleotide reductase activity and synergism with arabinofuranosylcytosine. Food and Chemical Toxicology 2017, 108 , 53-62. https://doi.org/10.1016/j.fct.2017.07.029
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