ACS Publications. Most Trusted. Most Cited. Most Read

OR SEARCH CITATIONS

My Activity
Publications
CONTENT TYPES

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:J. Med. Chem. 2012, 55, 16, 7230-7244
RETURN TO ISSUEPREVArticleNEXT

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

View Author Information
† 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
Request reuse permissions

    Article Views

    2413

    Altmetric

    -

    Citations

    154
    LEARN ABOUT THESE METRICS
    Read OnlinePDF (3 MB)
    Get e-Alerts
    Supporting Info (1)»
    SUBJECTS:

    Abstract

    Abstract Image

    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.

    Supporting Information

    ARTICLE SECTIONS
    Jump To

    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.

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    This article is cited by 154 publications.

    1. Juzheng Zhang, Ronghao Fang, Yanping Li, Jiamin Jin, Feng Yang, Jian Chen. Encapsulation of Au(III) Complex Using Lactoferrin Nanoparticles to Combat Glioma. Molecular Pharmaceutics 2023, 20 (7) , 3632-3644. https://doi.org/10.1021/acs.molpharmaceut.3c00239
    2. Zhenlei Zhang, Juzheng Zhang, Tongfu Yang, Shanhe Li, Gang Xu, Hong Liang, Feng Yang. Developing an Anticancer Platinum(II) Compound Based on the Uniqueness of Human Serum Albumin. Journal of Medicinal Chemistry 2023, 66 (8) , 5669-5684. https://doi.org/10.1021/acs.jmedchem.3c00001
    3. Mahendiran Dharmasivam, Busra Kaya, Tharushi Wijesinghe, Mahan Gholam Azad, Miguel A. Gonzálvez, Mohammad Hussaini, Jason Chekmarev, Paul V. Bernhardt, Des R. Richardson. Designing Tailored Thiosemicarbazones with Bespoke Properties: The Styrene Moiety Imparts Potent Activity, Inhibits Heme Center Oxidation, and Results in a Novel “Stealth Zinc(II) Complex”. Journal of Medicinal Chemistry 2023, 66 (2) , 1426-1453. https://doi.org/10.1021/acs.jmedchem.2c01600
    4. Wangbin Wu, Yu-Shien Sung, Elisa Tomat. Thiol-Reactive Arylsulfonate Masks for Phenolate Donors in Antiproliferative Iron Prochelators. Inorganic Chemistry 2022, 61 (49) , 19974-19982. https://doi.org/10.1021/acs.inorgchem.2c03250
    5. Enrico Falcone, Alessandra G. Ritacca, Sonja Hager, Hemma Schueffl, Bertrand Vileno, Youssef El Khoury, Petra Hellwig, Christian R. Kowol, Petra Heffeter, Emilia Sicilia, Peter Faller. Copper-Catalyzed Glutathione Oxidation is Accelerated by the Anticancer Thiosemicarbazone Dp44mT and Further Boosted at Lower pH. Journal of the American Chemical Society 2022, 144 (32) , 14758-14768. https://doi.org/10.1021/jacs.2c05355
    6. Juzheng Zhang, Zhenlei Zhang, Ming Jiang, Shanhe Li, Haoliang Yuan, Hongbin Sun, Feng Yang, Hong Liang. Developing a Novel Gold(III) Agent to Treat Glioma Based on the Unique Properties of Apoferritin Nanoparticles: Inducing Lethal Autophagy and Apoptosis. Journal of Medicinal Chemistry 2020, 63 (22) , 13695-13708. https://doi.org/10.1021/acs.jmedchem.0c01257
    7. Rukhsana Anjum, Duraippandi Palanimuthu, Danuta S. Kalinowski, William Lewis, Kyung Chan Park, Zaklina Kovacevic, Irfan Ullah Khan, Des R. Richardson. Synthesis, Characterization, and in Vitro Anticancer Activity of Copper and Zinc Bis(Thiosemicarbazone) Complexes. Inorganic Chemistry 2019, 58 (20) , 13709-13723. https://doi.org/10.1021/acs.inorgchem.9b01281
    8. Jun Wang, Yi Gou, Zhenlei Zhang, Ping Yu, Jinxu Qi, Qipin Qin, Hongbin Sun, Xiaoyang Wu, Hong Liang, Feng Yang. Developing an Anticancer Copper(II) Multitarget Pro-Drug Based on the His146 Residue in the IB Subdomain of Modified Human Serum Albumin. Molecular Pharmaceutics 2018, 15 (6) , 2180-2193. https://doi.org/10.1021/acs.molpharmaceut.8b00045
    9. Mirela F. Zaltariov, Marta Hammerstad, Homayon J. Arabshahi, Katarina Jovanović, Klaus W. Richter, Maria Cazacu, Sergiu Shova, Mihaela Balan, Niels H. Andersen, Siniša Radulović, Jóhannes Reynisson, K. Kristoffer Andersson, and Vladimir B. Arion . New Iminodiacetate–Thiosemicarbazone Hybrids and Their Copper(II) Complexes Are Potential Ribonucleotide Reductase R2 Inhibitors with High Antiproliferative Activity. Inorganic Chemistry 2017, 56 (6) , 3532-3549. https://doi.org/10.1021/acs.inorgchem.6b03178
    10. Arijit Basu, Yang-Sung Sohn, Mohamed Alyan, Rachel Nechushtai, Abraham J. Domb, and Amiram Goldblum . Discovering Novel and Diverse Iron-Chelators in Silico. Journal of Chemical Information and Modeling 2016, 56 (12) , 2476-2485. https://doi.org/10.1021/acs.jcim.6b00450
    11. Alexandra E. Stacy, Duraippandi Palanimuthu, Paul V. Bernhardt, Danuta S. Kalinowski, Patric J. Jansson, and Des R. Richardson . Structure–Activity Relationships of Di-2-pyridylketone, 2-Benzoylpyridine, and 2-Acetylpyridine Thiosemicarbazones for Overcoming Pgp-Mediated Drug Resistance. Journal of Medicinal Chemistry 2016, 59 (18) , 8601-8620. https://doi.org/10.1021/acs.jmedchem.6b01050
    12. Jinxu Qi, Yao Zhang, Yi Gou, Philbert Lee, Jun Wang, Shifang Chen, Zuping Zhou, Xiaoyang Wu, Feng Yang, and Hong Liang . Multidrug Delivery Systems Based on Human Serum Albumin for Combination Therapy with Three Anticancer Agents. Molecular Pharmaceutics 2016, 13 (9) , 3098-3105. https://doi.org/10.1021/acs.molpharmaceut.6b00277
    13. Jinxu Qi, Yi Gou, Yao Zhang, Kun Yang, Shifang Chen, Li Liu, Xiaoyang Wu, Tao Wang, Wei Zhang, and Feng Yang . Developing Anticancer Ferric Prodrugs Based on the N-Donor Residues of Human Serum Albumin Carrier IIA Subdomain. Journal of Medicinal Chemistry 2016, 59 (16) , 7497-7511. https://doi.org/10.1021/acs.jmedchem.6b00509
    14. Christian R. Kowol, Walter Miklos, Sarah Pfaff, Sonja Hager, Sebastian Kallus, Karla Pelivan, Mario Kubanik, Éva A. Enyedy, Walter Berger, Petra Heffeter, and Bernhard K. Keppler . Impact of Stepwise NH2-Methylation of Triapine on the Physicochemical Properties, Anticancer Activity, and Resistance Circumvention. Journal of Medicinal Chemistry 2016, 59 (14) , 6739-6752. https://doi.org/10.1021/acs.jmedchem.6b00342
    15. Alexandra E. Stacy, Duraippandi Palanimuthu, Paul V. Bernhardt, Danuta S. Kalinowski, Patric J. Jansson, and Des R. Richardson . Zinc(II)–Thiosemicarbazone Complexes Are Localized to the Lysosomal Compartment Where They Transmetallate with Copper Ions to Induce Cytotoxicity. Journal of Medicinal Chemistry 2016, 59 (10) , 4965-4984. https://doi.org/10.1021/acs.jmedchem.6b00238
    16. Zaynab Al-Eisawi, Christian Stefani, Patric J. Jansson, Akanksha Arvind, Philip C. Sharpe, Maram T. Basha, George M. Iskander, Naresh Kumar, Zaklina Kovacevic, Darius J. R. Lane, Sumit Sahni, Paul V. Bernhardt, Des R. Richardson, and Danuta S. Kalinowski . Novel Mechanism of Cytotoxicity for the Selective Selenosemicarbazone, 2-Acetylpyridine 4,4-Dimethyl-3-selenosemicarbazone (Ap44mSe): Lysosomal Membrane Permeabilization. Journal of Medicinal Chemistry 2016, 59 (1) , 294-312. https://doi.org/10.1021/acs.jmedchem.5b01399
    17. Moses Q. Wilks, Marc D. Normandin, Hushan Yuan, Hoonsung Cho, Yanyan Guo, Fanny Herisson, Cenk Ayata, Dustin W. Wooten, Georges El Fakhri, and Lee Josephson . Imaging PEG-Like Nanoprobes in Tumor, Transient Ischemia, and Inflammatory Disease Models. Bioconjugate Chemistry 2015, 26 (6) , 1061-1069. https://doi.org/10.1021/acs.bioconjchem.5b00213
    18. Zhao Deng, Des R. Richardson, . The Myc Family and the Metastasis Suppressor NDRG1: Targeting Key Molecular Interactions with Innovative Therapeutics. Pharmacological Reviews 2023, 75 (5) , 1007-1035. https://doi.org/10.1124/pharmrev.122.000795
    19. Periyanayagam Arockia Doss, Jebiti Haribabu, Nithya Balakrishnan, Srividya Swaminathan, Jose A. Pino, Nattamai Bhuvanesh, Ramasamy Karvembu. Cytotoxicity of copper(I) complexes containing indole‐based thiosemicarbazones and triphenylphosphine. ChemistrySelect 2023, 8 (29) https://doi.org/10.1002/slct.202301277
    20. Martin Schaier, Enrico Falcone, Tomas Prstek, Bertrand Vileno, Sonja Hager, Bernhard K Keppler, Petra Heffeter, Gunda Koellensperger, Peter Faller, Christian R Kowol. Human serum albumin as a copper source for anticancer thiosemicarbazones. Metallomics 2023, 15 (8) https://doi.org/10.1093/mtomcs/mfad046
    21. Faten Shehadeh-Tout, Heloisa H. Milioli, Suraya Roslan, Patric J. Jansson, Mahendiran Dharmasivam, Dinny Graham, Robin Anderson, Tharushi Wijesinghe, Mahan Gholam Azad, Des R. Richardson, Zaklina Kovacevic. Innovative thiosemicarbazones that induce multi-modal mechanisms to down-regulate estrogen-, progesterone-, androgen- and prolactin-receptors in breast cancer. Pharmacological Research 2023, 193 , 106806. https://doi.org/10.1016/j.phrs.2023.106806
    22. Elisa Tomat. Targeting iron to contrast cancer progression. Current Opinion in Chemical Biology 2023, 74 , 102315. https://doi.org/10.1016/j.cbpa.2023.102315
    23. Xiao Zhao, Des R. Richardson. The role of the NDRG1 in the pathogenesis and treatment of breast cancer. Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 2023, 1878 (3) , 188871. https://doi.org/10.1016/j.bbcan.2023.188871
    24. Yunyun Zheng, Kai Wei, Yingying Gao, Ziyan Zhou, Xinhua Zheng, Jiuling Li, Jinxu Qi. Comparative evaluation of the structure and antitumor mechanism of mononuclear and trinucleated thiosemicarbazone Cu(II) complexes. Journal of Inorganic Biochemistry 2023, 240 , 112116. https://doi.org/10.1016/j.jinorgbio.2022.112116
    25. Wenqian Wang, Kouichi Tabu, Alapati Aimaitijiang, Tetsuya Taga. Therapy-resistant nature of cancer stem cells in view of iron metabolism. Inflammation and Regeneration 2022, 42 (1) https://doi.org/10.1186/s41232-022-00220-y
    26. Vaibhavi Joshi, Sunil R. Lakhani, Amy E. McCart Reed. NDRG1 in Cancer: A Suppressor, Promoter, or Both?. Cancers 2022, 14 (23) , 5739. https://doi.org/10.3390/cancers14235739
    27. Andrew Carter, Seth Racey, Stephany Veuger. The Role of Iron in DNA and Genomic Instability in Cancer, a Target for Iron Chelators That Can Induce ROS. Applied Sciences 2022, 12 (19) , 10161. https://doi.org/10.3390/app121910161
    28. Muhammad Ismail, Wen Yang, Yanfei Li, Yibin Wang, Wenya He, Jiefei Wang, Pir Muhammad, Timothy B. Chaston, Fawad Ur Rehman, Meng Zheng, David B. Lovejoy, Bingyang Shi. Biomimetic Dp44mT-nanoparticles selectively induce apoptosis in Cu-loaded glioblastoma resulting in potent growth inhibition. Biomaterials 2022, 289 , 121760. https://doi.org/10.1016/j.biomaterials.2022.121760
    29. Xian-Guang Bai, Yunyun Zheng, Jinxu Qi. Advances in thiosemicarbazone metal complexes as anti-lung cancer agents. Frontiers in Pharmacology 2022, 13 https://doi.org/10.3389/fphar.2022.1018951
    30. Maria Krchniakova, Silvia Paukovcekova, Petr Chlapek, Jakub Neradil, Jan Skoda, Renata Veselska. Thiosemicarbazones and selected tyrosine kinase inhibitors synergize in pediatric solid tumors: NDRG1 upregulation and impaired prosurvival signaling in neuroblastoma cells. Frontiers in Pharmacology 2022, 13 https://doi.org/10.3389/fphar.2022.976955
    31. Silvia Paukovcekova, Maria Krchniakova, Petr Chlapek, Jakub Neradil, Jan Skoda, Renata Veselska. Thiosemicarbazones Can Act Synergistically with Anthracyclines to Downregulate CHEK1 Expression and Induce DNA Damage in Cell Lines Derived from Pediatric Solid Tumors. International Journal of Molecular Sciences 2022, 23 (15) , 8549. https://doi.org/10.3390/ijms23158549
    32. Mahendiran Dharmasivam, Mahan Gholam Azad, Rizwana Afroz, Vera Richardson, Patric J. Jansson, Des R. Richardson. The thiosemicarbazone, DpC, broadly synergizes with multiple anti-cancer therapeutics and demonstrates temperature- and energy-dependent uptake by tumor cells. Biochimica et Biophysica Acta (BBA) - General Subjects 2022, 1866 (8) , 130152. https://doi.org/10.1016/j.bbagen.2022.130152
    33. DR Richardson, M Gholam Azad, R Afroz, V Richardson, M Dharmasivam. Thiosemicarbazones reprogram pancreatic cancer bidirectional oncogenic signaling between cancer cells and stellate cells to suppress desmoplasia. Future Medicinal Chemistry 2022, 14 (13) , 1005-1017. https://doi.org/10.4155/fmc-2022-0050
    34. Marta Ribeiro, Cátia A. Sousa, Manuel Simões. Harnessing microbial iron chelators to develop innovative therapeutic agents. Journal of Advanced Research 2022, 39 , 89-101. https://doi.org/10.1016/j.jare.2021.10.010
    35. Jaehee Kim, Areum Park, Jieon Hwang, Xianghua Zhao, Jaesung Kwak, Hyun Woo Kim, Minhee Ku, Jaemoon Yang, Tae Il Kim, Kyu-Sung Jeong, Uyeong Choi, Hyuk Lee, Sang Joon Shin. KS10076, a chelator for redox-active metal ions, induces ROS-mediated STAT3 degradation in autophagic cell death and eliminates ALDH1+ stem cells. Cell Reports 2022, 40 (3) , 111077. https://doi.org/10.1016/j.celrep.2022.111077
    36. Winaki P Sohtun, Arunkumar Kathiravan, Mariadoss Asha Jhonsi, Md. Aashique, Soumen Bera, Marappan Velusamy. Synthesis, crystal structure, BSA binding and antibacterial studies of Ni(II) complexes derived from dithiocarbazate based ligands. Inorganica Chimica Acta 2022, 536 , 120888. https://doi.org/10.1016/j.ica.2022.120888
    37. Yunyun Zheng, Bin Li, Yu Ai, Mengyao Chen, Xinhua Zheng, Jinxu Qi. Synthesis, crystal structures and anti-cancer mechanism of Cu(II) complex derived from 2-acetylpyrazine thiosemicarbazone. Journal of Coordination Chemistry 2022, 75 (9-10) , 1325-1340. https://doi.org/10.1080/00958972.2022.2111660
    38. Ya-Ting Chen, Shao-Nan Zhang, Zhen-Feng Wang, Qing-Min Wei, Shu-Hua Zhang. Discovery of thirteen cobalt( ii ) and copper( ii ) salicylaldehyde Schiff base complexes that induce apoptosis and autophagy in human lung adenocarcinoma A549/DDP cells and that can overcome cisplatin resistance in vitro and in vivo. Dalton Transactions 2022, 51 (10) , 4068-4078. https://doi.org/10.1039/D1DT03749H
    39. Bekesho Geleta, Faten S. Tout, Syer Choon Lim, Sumit Sahni, Patric J. Jansson, Minoti V. Apte, Des R. Richardson, Žaklina Kovačević. Targeting Wnt/tenascin C-mediated cross talk between pancreatic cancer cells and stellate cells via activation of the metastasis suppressor NDRG1. Journal of Biological Chemistry 2022, 298 (3) , 101608. https://doi.org/10.1016/j.jbc.2022.101608
    40. Tharushi P. Wijesinghe, Mahendiran Dharmasivam, Charles C. Dai, Des R. Richardson. Innovative therapies for neuroblastoma: The surprisingly potent role of iron chelation in up-regulating metastasis and tumor suppressors and down-regulating the key oncogene, N-myc. Pharmacological Research 2021, 173 , 105889. https://doi.org/10.1016/j.phrs.2021.105889
    41. Maura Pellei, Fabio Del Bello, Marina Porchia, Carlo Santini. Zinc coordination complexes as anticancer agents. Coordination Chemistry Reviews 2021, 445 , 214088. https://doi.org/10.1016/j.ccr.2021.214088
    42. Yu‐Shien Sung, Wangbin Wu, Megan A. Ewbank, Rachel D. Utterback, Michael T. Marty, Elisa Tomat. Albumin Conjugates of Thiosemicarbazone and Imidazole‐2‐thione Prochelators: Iron Coordination and Antiproliferative Activity. ChemMedChem 2021, 16 (18) , 2764-2768. https://doi.org/10.1002/cmdc.202100278
    43. Jason Chekmarev, Mahan Gholam Azad, Des R. Richardson. The Oncogenic Signaling Disruptor, NDRG1: Molecular and Cellular Mechanisms of Activity. Cells 2021, 10 (9) , 2382. https://doi.org/10.3390/cells10092382
    44. Maria V. Babak, Dohyun Ahn. Modulation of Intracellular Copper Levels as the Mechanism of Action of Anticancer Copper Complexes: Clinical Relevance. Biomedicines 2021, 9 (8) , 852. https://doi.org/10.3390/biomedicines9080852
    45. Yelda Bingöl Alpaslan, Yusuf Sert, Winaki P. Sohtun, Marappan Velusamy, Halil Gökce. Structural, spectral, electronic, and molecular docking investigations on N , N ‐dimethyl ‐2‐[( 1E )‐({[(methylsulfanyl)methanethioyl]amino}imino)methyl]aniline. Journal of the Chinese Chemical Society 2021, 68 (6) , 971-988. https://doi.org/10.1002/jccs.202000435
    46. Jia-Qi Li, Han Gao, Le Zhai, Le-Yun Sun, Cheng Chen, Jia-Zhu Chigan, Huan-Huan Ding, Ke-Wu Yang. Dipyridyl-substituted thiosemicarbazone as a potent broad-spectrum inhibitor of metallo-β-lactamases. Bioorganic & Medicinal Chemistry 2021, 38 , 116128. https://doi.org/10.1016/j.bmc.2021.116128
    47. Eda R. Machado, Ida Annunziata, Diantha van de Vlekkert, Gerard C. Grosveld, Alessandra d’Azzo. Lysosomes and Cancer Progression: A Malignant Liaison. Frontiers in Cell and Developmental Biology 2021, 9 https://doi.org/10.3389/fcell.2021.642494
    48. Bekesho Geleta, Kyung Chan Park, Patric J. Jansson, Sumit Sahni, Sanaz Maleki, Zhihong Xu, Takashi Murakami, Marina Pajic, Minoti V. Apte, Des R. Richardson, Zaklina Kovacevic. Breaking the cycle: Targeting of NDRG1 to inhibit bi‐directional oncogenic cross‐talk between pancreatic cancer and stroma. The FASEB Journal 2021, 35 (2) https://doi.org/10.1096/fj.202002279R
    49. Bing Zhao, Xinhui Zhang, Tingting Yu, Ying Liu, Xiaoling Zhang, Yongfang Yao, Xuejian Feng, Hongmin Liu, Dequan Yu, Liying Ma, Shangshang Qin. Discovery of thiosemicarbazone derivatives as effective New Delhi metallo-β-lactamase-1 (NDM-1) inhibitors against NDM-1 producing clinical isolates. Acta Pharmaceutica Sinica B 2021, 11 (1) , 203-221. https://doi.org/10.1016/j.apsb.2020.07.005
    50. Zhang-Xu He, Jin-Ling Huo, Yun-Peng Gong, Qi An, Xin Zhang, Hui Qiao, Fei-Fei Yang, Xin-Hui Zhang, Le-Min Jiao, Hong-Min Liu, Li-Ying Ma, Wen Zhao. Design, synthesis and biological evaluation of novel thiosemicarbazone-indole derivatives targeting prostate cancer cells. European Journal of Medicinal Chemistry 2021, 210 , 112970. https://doi.org/10.1016/j.ejmech.2020.112970
    51. Junmin Zhang, Dongzhu Duan, Zi‐Long Song, Tianyu Liu, Yanan Hou, Jianguo Fang. Small molecules regulating reactive oxygen species homeostasis for cancer therapy. Medicinal Research Reviews 2021, 41 (1) , 342-394. https://doi.org/10.1002/med.21734
    52. Silvia Paukovcekova, Jan Skoda, Jakub Neradil, Erika Mikulenkova, Petr Chlapek, Jaroslav Sterba, Des R. Richardson, Renata Veselska. Novel Thiosemicarbazones Sensitize Pediatric Solid Tumor Cell-Types to Conventional Chemotherapeutics through Multiple Molecular Mechanisms. Cancers 2020, 12 (12) , 3781. https://doi.org/10.3390/cancers12123781
    53. Dong-Hun Bae, Darius J.R. Lane, Aritee R. Siafakas, Robert Sutak, Jasmina Paluncic, Michael L.H. Huang, Patric J. Jansson, Yohan Suryo Rahmanto, Des R. Richardson. Acireductone dioxygenase 1 (ADI1) is regulated by cellular iron by a mechanism involving the iron chaperone, PCBP1, with PCBP2 acting as a potential co-chaperone. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2020, 1866 (10) , 165844. https://doi.org/10.1016/j.bbadis.2020.165844
    54. Ola Ibrahim, Jeff O’Sullivan. Iron chelators in cancer therapy. BioMetals 2020, 33 (4-5) , 201-215. https://doi.org/10.1007/s10534-020-00243-3
    55. Narendra Kumar Singh, Anupa A Kumbhar, Yuba Raj Pokharel, Paras Nath Yadav. Anticancer potency of copper(II) complexes of thiosemicarbazones. Journal of Inorganic Biochemistry 2020, 210 , 111134. https://doi.org/10.1016/j.jinorgbio.2020.111134
    56. Kyung Chan Park, Mahendiran Dharmasivam, Des R. Richardson. The Role of Extracellular Proteases in Tumor Progression and the Development of Innovative Metal Ion Chelators That Inhibit Their Activity. International Journal of Molecular Sciences 2020, 21 (18) , 6805. https://doi.org/10.3390/ijms21186805
    57. Syer C. Lim, Patric J. Jansson, Stephen J. Assinder, Sanaz Maleki, Des R. Richardson, Zaklina Kovacevic. Unique targeting of androgen‐dependent and ‐independent AR signaling in prostate cancer to overcome androgen resistance. The FASEB Journal 2020, 34 (9) , 11511-11528. https://doi.org/10.1096/fj.201903167R
    58. Sonja Hager, Veronika F.S. Pape, Vivien Pósa, Bianca Montsch, Lukas Uhlik, Gergely Szakács, Szilárd Tóth, Nikolett Jabronka, Bernhard K. Keppler, Christian R. Kowol, Éva A. Enyedy, Petra Heffeter. High Copper Complex Stability and Slow Reduction Kinetics as Key Parameters for Improved Activity, Paraptosis Induction, and Impact on Drug-Resistant Cells of Anticancer Thiosemicarbazones. Antioxidants & Redox Signaling 2020, 33 (6) , 395-414. https://doi.org/10.1089/ars.2019.7854
    59. Sumit Sahni, Josef Gillson, Kyung Chan Park, Shannon Chiang, Lionel Yi Wen Leck, Patric J. Jansson, Des R. Richardson. NDRG1 suppresses basal and hypoxia-induced autophagy at both the initiation and degradation stages and sensitizes pancreatic cancer cells to lysosomal membrane permeabilization. Biochimica et Biophysica Acta (BBA) - General Subjects 2020, 1864 (8) , 129625. https://doi.org/10.1016/j.bbagen.2020.129625
    60. Xin-Hui Zhang, Bo-Wang, Yuan-Yuan Tao, Qin Ma, Hao-Jie Wang, Zhang-Xu He, Hui-Pan Wu, Yi-Han Li, Bing Zhao, Li-Ying Ma, Hong-Min Liu. Thiosemicarbazone-based lead optimization to discover high-efficiency and low-toxicity anti-gastric cancer agents. European Journal of Medicinal Chemistry 2020, 199 , 112349. https://doi.org/10.1016/j.ejmech.2020.112349
    61. Jinpeng Zhou, Yang Jiang, Junshuang Zhao, Haiying Zhang, Jinlong Fu, Peng Luo, Yanju Ma, Dan Zou, Huiling Gao, Jiangfeng Hu, Ye Zhang, Zhitao Jing. Dp44mT, an iron chelator, suppresses growth and induces apoptosis via RORA-mediated NDRG2-IL6/JAK2/STAT3 signaling in glioma. Cellular Oncology 2020, 43 (3) , 461-475. https://doi.org/10.1007/s13402-020-00502-y
    62. Jinxu Qi, Taichen Liu, Wei Zhao, Xinhua Zheng, Yihong Wang. Synthesis, crystal structure and antiproliferative mechanisms of gallium( iii ) complexes with benzoylpyridine thiosemicarbazones. RSC Advances 2020, 10 (32) , 18553-18559. https://doi.org/10.1039/D0RA02913K
    63. Bhushan Shakya, Paras Nath Yadav. Thiosemicarbazones as Potent Anticancer Agents and their Modes of Action. Mini-Reviews in Medicinal Chemistry 2020, 20 (8) , 638-661. https://doi.org/10.2174/1389557519666191029130310
    64. 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
    65. 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
    66. 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
    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. 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
    69. 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
    70. 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
    71. 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
    72. 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
    73. 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
    74. 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
    75. 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
    76. 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
    77. 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
    78. 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
    79. 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
    80. 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
    81. 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
    82. 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
    83. 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
    84. 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
    85. 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
    86. 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
    87. 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
    88. 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
    89. 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
    90. 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
    91. 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
    92. 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
    93. 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
    94. 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
    95. 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
    96. 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
    97. 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
    98. Mohammed Bakir, Mark A. W. Lawrence, Marhoun Ferhat, Rebecca R. Conry. Spectroscopic, electrochemical and X-ray crystallographic properties of a novel palladium(II) complex of thioamide deprotonated di-2-pyridyl ketone thiosemicarbazone (dpktsc-H) −. Journal of Coordination Chemistry 2017, 70 (17) , 3048-3064. https://doi.org/10.1080/00958972.2017.1374379
    99. Sharleen V. Menezes, Sumit Sahni, Zaklina Kovacevic, Des R. Richardson. Interplay of the iron-regulated metastasis suppressor NDRG1 with epidermal growth factor receptor (EGFR) and oncogenic signaling. Journal of Biological Chemistry 2017, 292 (31) , 12772-12782. https://doi.org/10.1074/jbc.R117.776393
    100. Henning Karlsson, Mårten Fryknäs, Sara Strese, Joachim Gullbo, Gunnar Westman, Ulf Bremberg, Tobias Sjöblom, Tatjana Pandzic, Rolf Larsson, Peter Nygren. Mechanistic characterization of a copper containing thiosemicarbazone with potent antitumor activity. Oncotarget 2017, 8 (18) , 30217-30234. https://doi.org/10.18632/oncotarget.16324
    Load all citations
    Download PDF

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    Pair your accounts.

    Export articles to Mendeley

    Get article recommendations from ACS based on references in your Mendeley library.

    You’ve supercharged your research process with ACS and Mendeley!

    STEP 1:
    Click to create an ACS ID

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

    MENDELEY PAIRING EXPIRED
    Your Mendeley pairing has expired. Please reconnect