Citation: Sreekanth Thota, Srujana Vallala, Rajeshwar Yerra, Eliezer J. Barreiro. Design, synthesis, characterization, cytotoxic and structure activity relationships of novel Ru(II) complexes[J]. Chinese Chemical Letters, ;2015, 26(6): 721-726. doi: 10.1016/j.cclet.2015.03.011 shu

Design, synthesis, characterization, cytotoxic and structure activity relationships of novel Ru(II) complexes

a National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fundação Oswaldo Cruz, Ministério da Saúde, Av.
a National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Fundação Oswaldo Cruz, Ministério da Saúde, Av. Brasil 4036, Prédio da Expansão, 88 Andar, Sala 814, Manguinhos, 21040-361 Rio de Janeiro, RJ, Brazil;
b S.
b S.R. College of Pharmacy, Department of Pharmaceutical Chemistry & Toxicology, Ananthasagar, Warangal, Telangana 506371, India;
3.
c Programa de Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

Corresponding author: Sreekanth Thota,
Received Date: 12 December 2014
Available Online: 27 February 2015
Fund Project: Coordenaç (CNPq) Oswaldo Cruz Foundation (Fiocruz) (CAPES)Department of Science and Technology, New Delhi, India [No. SR/WOS-A/LS-562/2011) dated 27/03/2012]. (Fiocruz)

Platinum containing compounds have shown antineoplastic potential, but their clinical applications have been limited by high toxicity. Ruthenium containing complexes have long been known to be well suited for biological applications, and have long been utilized as replacements to popular platinum based-drugs. Here, we report a novel series of ruthenium(II) arene compounds bearing thiosemicarbazone and isonicotinylhydrazone ligands with potent anticancer activity their structure activity relationships and apoptosis was studied. The cytotoxic activity of the new ruthenium(II) arene compounds has been evaluated in several cell lines (Molt 4/C₈, L1210, CEM, HL60 and BEL7402). Among them, ten complexes were found to be excellent in vitro growth inhibitory activity against various cell lines with IC₅₀ in the sub-micromolar range.
- Cytotoxic,
- Ligand,
- Ruthenium compounds,
- Structure activity relationships
1. [1]
  [1] M. Patra, G. Gasser, Organometallic compounds: an opportunity for chemical biology? ChemBioChem 13 (2012) 1232-1252.
2. [2]
  [2] N.P. Barry, P.J. Sadler, Challenges for metals in medicine: how nanotechnology may help to shape the future, ACS Nano 7 (2013) 5654-5659.
3. [3]
  [3] C.M. Clavel, E. Păunescu, P. Nowak-Sliwinska, et al., Discovery of a highly tumorselective organometallic ruthenium(II)-arene complex, J. Med. Chem. 57 (2014) 3546-3558.
4. [4]
  [4] C.G. Hartinger, M.A. Jakupec, S. Zorbas-Seifried, et al., KP1019, a new redox-active anticancer agent-preclinical development and results of a clinical phase I study in tumor patients, Chem. Biodivers. 5 (2008) 2140-2155.
5. [5]
  [5] I. Romero-Canelón, L. Salassa, P.J. Sadler, The contrasting activity of iodido versus chlorido ruthenium and osmium arene azo-and imino-pyridine anticancer complexes: control of cell selectivity, cross-resistance, p53 dependence, and apoptosis pathway, J. Med. Chem. 56 (2013) 1291-1300.
6. [6]
  [6] G.S. Smith, B. Therrien, Targeted and multifunctional arene ruthenium chemotherapeutics, Dalton Trans. 40 (2011) 10793-10800.
7. [7]
  [7] D.S. Kalinowski, P. Quach, D.R. Richardson, Thiosemicarbazones: the new wave in cancer treatment, Future Med. Chem. 1 (2009) 1143-1151.
8. [8]
  [8] D.R. Richardson, D.S. Kalinowski, V. Richardson, et al., 2-Acetylpyridine thiosemicarbazones are potent iron chelators and antiproliferative agents: redox activity, iron complexation and characterization of their antitumor activity, J. Med. Chem. 52 (2009) 1459-1470.
9. [9]
  [9] B.M. Zeglis, V. Divilov, J.S. Lewis, Role of metalation in the topoisomerase IIa inhibition and antiproliferation activity of a series of α-heterocyclic-N⁴-substituted thiosemicarbazones and their Cu(II) complexes, J. Med. Chem. 54 (2011) 2391-2398.
10. [10]
  [10] J. Liu, W.J. Zhen, S. Shi, et al., Synthesis, antitumor activity and structure-activity relationships of a series of Ru(II) complexes, J. Inorg. Biochem. 102 (2008) 193-202.
11. [11]
  [11] U. Schatzschneider, J. Niesel, I. Ott, et al., Cellular uptake, cytotoxicity, and metabolic profiling of human cancer cells treated with ruthenium(II) polypyridyl complexes [Ru(bpy)₂(N-N)]Cl₂ with N-N = bpy, phen, dpq, dppz, and dppn, ChemMedChem 3 (2008) 1104-1109.
12. [12]
  [12] Y.J. Liu, C.H. Zeng, H.L. Huang, L.X. He, F.H. Wu, Synthesis, DNA-binding, photocleavage, cytotoxicity and antioxidant activity of ruthenium(II) polypyridyl complexes, Eur. J. Med. Chem. 45 (2010) 564-571.
13. [13]
  [13] C.M. Kepert, G.B. Decon, N. Sahely, et al., Synthesis of heteroleptic bis(diimine)-carbonylchlororuthenium(II) complexes from photodecarbonylated precursors, Inorg. Chem. 43 (2004) 2818-2827.
14. [14]
  [14] C.P. Tan, J. Liu, H. Li, et al., Differences in structure, physiological stability, electrochemistry, cytotoxicity, DNA and protein binding properties between two Ru(III) complexes, J. Inorg. Biochem. 102 (2008) 347-358.
15. [15]
  [15] S.S. Karki, S. Thota, A. Katiyar, et al., Synthesis, characterization and cytotoxic activity of some Ru(II) complexes, Turk. J. Pharm. Sci. 8 (2011) 207-218.
16. [16]
  [16] C.P. Tan, S. Lai, S.H. Wu, et al., Nuclear permeable ruthenium(II) b-carboline complexes induce autophagy to antagonize mitochondrial-mediated apoptosis, J. Med. Chem. 53 (2010) 7613-7624.
17. [17]
  [17] F. Caruso, E. Monti, J. Matthews, et al., Synthesis, characterization, and antitumor activity of water-soluble (arene)ruthenium(II) derivatives of 1,3-dimethyl-4-acylpyrazolon-5-ato ligands. First example of Ru(arene)(ligand) antitumor species involving simultaneous Ru-N7(guanine) bonding and ligand intercalation to DNA, Inorg. Chem. 53 (2014) 3668-3677.
18. [18]
  [18] S. Thota, M. Imran, M. Udugula, et al., Synthesis, spectroscopic characterization and in vitro antitumor activities of some novel mononuclear Ru(II) complexes, Chin. Chem. Lett. 23 (2012) 466-469.
19. [19]
  [19] S. Thota, S.S. Karki, K.N. Jayaveera, J. Balzarini, E. De Clercq, Synthesis, characterization, antitumor, and cytotoxic activity of mononuclear Ru(II) complexes, J. Coord. Chem. 63 (2010) 4332-4346.
20. [20]
  [20] S. Thota, S.S. Karki, K.N. Jayaveera, J. Balzarini, E. De Clercq, Synthesis, antineoplastic and cytotoxic activities of some mononuclear Ru(II) complexes, J. Enzyme Inhib. Med. Chem. 25 (2010) 513-519.
21. [21]
  [21] S.S. Karki, S. Thota, S.Y. Darj, J. Balzarini, E. De Clercq, Synthesis, anticancer, and cytotoxic activities of some mononuclear Ru(II) compounds, Bioorg. Med. Chem. 15 (2007) 6632-6641.
22. [22]
  [22] J.A. Hickman, Apoptosis induced by anticancer drugs, Cancer Metastasis Rev. 11 (1992) 121-139.
23. [23]
  [23] K. Gangarapu, S. Manda, S. Thota, et al., Microwave assisted synthesis, characterization of some new isatin and thiophene derivatives as cytotoxic and chemopreventive agents, Lett. Drug Des. Discov. 9 (2012) 934-941.
1. [1]
  Guo-Ping Yin , Ya-Juan Li , Li Zhang , Ling-Gao Zeng , Xue-Mei Liu , Chang-Hua Hu . Citrinsorbicillin A, a novel homotrimeric sorbicillinoid isolated by LC-MS-guided with cytotoxic activity from the fungus Trichoderma citrinoviride HT-9. Chinese Chemical Letters, 2024, 35(8): 109035-. doi: 10.1016/j.cclet.2023.109035
2. [2]
  Jian Song , Shenghui Wang , Qiuge Liu , Xiao Wang , Shuo Yuan , Hongmin Liu , Saiyang Zhang . N-Benzyl arylamide derivatives as novel and potent tubulin polymerization inhibitors against gastric cancers: Design, structure–activity relationships and biological evaluations. Chinese Chemical Letters, 2025, 36(2): 109678-. doi: 10.1016/j.cclet.2024.109678
3. [3]
  Tao Yu , Vadim A. Soloshonok , Zhekai Xiao , Hong Liu , Jiang Wang . Probing the dynamic thermodynamic resolution and biological activity of Cu(Ⅱ) and Pd(Ⅱ) complexes with Schiff base ligand derived from proline. Chinese Chemical Letters, 2024, 35(4): 108901-. doi: 10.1016/j.cclet.2023.108901
4. [4]
  Ziyi Liu , Xunying Liu , Lubing Qin , Haozheng Chen , Ruikai Li , Zhenghua Tang . Alkynyl ligand for preparing atomically precise metal nanoclusters: Structure enrichment, property regulation, and functionality enhancement. Chinese Journal of Structural Chemistry, 2024, 43(11): 100405-100405. doi: 10.1016/j.cjsc.2024.100405
5. [5]
  Xiaofen GUAN , Yating LIU , Jia LI , Yiwen HU , Haiyuan DING , Yuanjing SHI , Zhiqiang WANG , Wenmin WANG . Synthesis, crystal structure, and DNA-binding of binuclear lanthanide complexes based on a multidentate Schiff base ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2486-2496. doi: 10.11862/CJIC.20240122
6. [6]
  Haiming Wu , Gaya N. Andrew , Rajini Anumula , Zhixun Luo . Corrigendum to 'How ligand coordination and superatomic-states accommodate the structure and property of a metal cluster: Cu₄ (dppy)₄ Cl₂ vs. Cu₂₁ (dppy)₁₀ with altered photoluminescence' [Chin. Chem. Lett. 35 (2024) 108340]. Chinese Chemical Letters, 2024, 35(12): 109912-. doi: 10.1016/j.cclet.2024.109912
7. [7]
  Kongchuan Wu , Dandan Lu , Jianbin Lin , Ting-Bin Wen , Wei Hao , Kai Tan , Hui-Jun Zhang . Elucidating ligand effects in rhodium(Ⅲ)-catalyzed arene–alkene coupling reactions. Chinese Chemical Letters, 2024, 35(5): 108906-. doi: 10.1016/j.cclet.2023.108906
8. [8]
  Yuanjin Chen , Xianghui Shi , Dajiang Huang , Junnian Wei , Zhenfeng Xi . Synthesis and reactivity of cobalt dinitrogen complex supported by nonsymmetrical pincer ligand. Chinese Chemical Letters, 2024, 35(7): 109292-. doi: 10.1016/j.cclet.2023.109292
9. [9]
  Luyao Lu , Chen Zhu , Fei Li , Pu Wang , Xi Kang , Yong Pei , Manzhou Zhu . Ligand effects on geometric structures and catalytic activities of atomically precise copper nanoclusters. Chinese Journal of Structural Chemistry, 2024, 43(10): 100411-100411. doi: 10.1016/j.cjsc.2024.100411
10. [10]
  Tiantian Gong , Yanan Chen , Shuo Wang , Miao Wang , Junwei Zhao . Rigid-flexible-ligand-ornamented lanthanide-incorporated selenotungstates and photoluminescence properties. Chinese Journal of Structural Chemistry, 2024, 43(9): 100370-100370. doi: 10.1016/j.cjsc.2024.100370
11. [11]
  Junxin Li , Chao Chen , Yuzhen Dong , Jian Lv , Jun-Mei Peng , Yuan-Ye Jiang , Daoshan Yang . Ligand-promoted reductive coupling between aryl iodides and cyclic sulfonium salts by nickel catalysis. Chinese Chemical Letters, 2024, 35(11): 109732-. doi: 10.1016/j.cclet.2024.109732
12. [12]
  Zhibin Ren , Shan Li , Xiaoying Liu , Guanghao Lv , Lei Chen , Jingli Wang , Xingyi Li , Jiaqing Wang . Penetrating efficiency of supramolecular hydrogel eye drops: Electrostatic interaction surpasses ligand-receptor interaction. Chinese Chemical Letters, 2024, 35(11): 109629-. doi: 10.1016/j.cclet.2024.109629
13. [13]
  Peipei CUI , Xin LI , Yilin CHEN , Zhilin CHENG , Feiyan GAO , Xu GUO , Wenning YAN , Yuchen DENG . Transition metal coordination polymers with flexible dicarboxylate ligand: Synthesis, characterization, and photoluminescence property. Chinese Journal of Inorganic Chemistry, 2024, 40(11): 2221-2231. doi: 10.11862/CJIC.20240234
14. [14]
  Jumei Zhang , Ziheng Zhang , Gang Li , Hongjin Qiao , Hua Xie , Ling Jiang . Ligand-mediated reactivity in CO oxidation of yttrium-nickel monoxide carbonyl complexes. Chinese Chemical Letters, 2025, 36(2): 110278-. doi: 10.1016/j.cclet.2024.110278
15. [15]
  Yao HUANG , Yingshu WU , Zhichun BAO , Yue HUANG , Shangfeng TANG , Ruixue LIU , Yancheng LIU , Hong LIANG . Copper complexes of anthrahydrazone bearing pyridyl side chain: Synthesis, crystal structure, anticancer activity, and DNA binding. Chinese Journal of Inorganic Chemistry, 2025, 41(1): 213-224. doi: 10.11862/CJIC.20240359
16. [16]
  Ruowen Liang , Chao Zhang , Guiyang Yan . Enhancing CO2 cycloaddition through ligand functionalization: A case study of UiO-66 metal-organic frameworks. Chinese Journal of Structural Chemistry, 2024, 43(2): 100211-100211. doi: 10.1016/j.cjsc.2023.100211
17. [17]
  Mei Peng , Wei-Min He . Photochemical synthesis and group transfer reactions of azoxy compounds. Chinese Chemical Letters, 2024, 35(8): 109899-. doi: 10.1016/j.cclet.2024.109899
18. [18]
  Wei Sun , Anjing Liao , Li Lei , Xu Tang , Ya Wang , Jian Wu . Research progress on piperidine-containing compounds as agrochemicals. Chinese Chemical Letters, 2025, 36(1): 109855-. doi: 10.1016/j.cclet.2024.109855
19. [19]
  Xinlong Han , Huiying Zeng , Chao-Jun Li . Trifluoromethylative homo-coupling of carbonyl compounds. Chinese Chemical Letters, 2025, 36(1): 109817-. doi: 10.1016/j.cclet.2024.109817
20. [20]
  Qiyan Wu , Ruixin Zhou , Zhangyi Yao , Tanyuan Wang , Qing Li . Effective approaches for enhancing the stability of ruthenium-based electrocatalysts towards acidic oxygen evolution reaction. Chinese Chemical Letters, 2024, 35(10): 109416-. doi: 10.1016/j.cclet.2023.109416

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(592)
HTML views(13)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142