Citation: Wei SU, Bao-Qu ZHANG, Bing-Hua PENG, Zhao-Feng TANG, Pei-Yuan LI. Synthesis and Anticancer Activity of a New Di-nuclear Ruthenium Arene Compound with Thiosemicarbazones[J]. Chinese Journal of Structural Chemistry, ;2020, 39(6): 1112-1118. doi: 10.14102/j.cnki.0254-5861.2011-2606 shu

Synthesis and Anticancer Activity of a New Di-nuclear Ruthenium Arene Compound with Thiosemicarbazones

a.
Key Laboratory of Guangxi Key Laboratory of Natural Polymer Chemistry and Physics (Nanning Normal University), Nanning 530001, China
b.
College of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530200, China

Corresponding author: Pei-Yuan LI, lipearpear@163.com
Received Date: 19 September 2019
Accepted Date: 13 January 2020

Fund Project: the National Natural Science Foundation of China 51961009the National Natural Science Foundation of China 21761006Natural Science Foundation of Guangxi Province 2017GXNSFAA198335Natural Science Foundation of Guangxi Province 2018GXNSFAA281345Guangxi Scientific and Technological Development Projects AD17195081"BAGUI Scholar" Program of Guangxi Province, Natural Science Foundation of Guangxi University of Chinese Medicine 2017JQ001Guangxi First-class Discipline: Chinese Materia Medica Scientific Research of Guangxi Education Department [2018] No. 12Research Project of Guangxi First-class Discipline 2019XK135Project of Guangxi Key Laboratory of Zhuang and Yao Ethnic Medicine GXZYZZ2019-4

Figures(5)

A new di-nuclear ruthenium arene compound containing thiosemicarbazone ligands, [Ru(η⁶-cymene)(TSC)Cl]₂(PF₆)₂ (2), was synthesized and characterized by ¹H NMR, HR-ESI-MS, and elemental analysis. Furthermore, the complete structure of 2 was determined by single-crystal X-ray diffraction analysis. Density functional theory (DFT) calculations with B3LYP functional and LANL2DZ (for Ru)/6-31G* (for other atoms) basis sets were carried out for the reactions involving complexes 1 and 2 in order to understand the formation of the complexes. The in vitro anticancer activities of the compound were investigated against five human cancer cell lines (SGC-7901, CNE-2, HepG2, KB and HeLa), and the IC₅₀ values are 39.5, 45.8, 49.8, 54.5 and 61.8 μM, respectively.
- ruthenium,
- compound,
- DFT,
- anticancer
1. [1]
  Nagle, A. S.; Khare, S.; Kumar, A. B.; Supek, F.; Buchynskyy, A.; Mathison, C. J. N.; Chennamaneni, N. K.; Pendem, N; Buckner, F. S.; Gelb, M. H.; Molteni, V. Recent developments in drug discovery for leishmaniasis and human african trypanosomiasis. Chem. Rev. 2014, 114, 11305–11347. doi: 10.1021/cr500365f
2. [2]
  Stacy, A. E.; Palanimuthu, D.; Bernhardt, P. V.; Kalinowski, D. S.; Jansson, P. J.; Richardson, D. R. Structure–Activity relationships of di-2-pyridylketone, 2-benzoylpyridine, and 2-acetylpyridine thiosemicarbazones for overcoming pgp-Mediated drug resistance. J. Med. Chem. 2016, 59, 8601–8620. doi: 10.1021/acs.jmedchem.6b01050
3. [3]
  Qi, J.; Gou, Y.; Zhang, Y.; Yang, K.; Chen, S.; Liu, L.; Wu, X.; Wang, T.; Zhang, W.; Yang, F. Developing anticancer ferric prodrugs based on the N-donor residues of human serum albumin carrier (Ⅱ) A subdomain. J. Med. Chem. 2016, 59, 7497–7511. doi: 10.1021/acs.jmedchem.6b00509
4. [4]
  Zaltariov, M. F.; Hammerstad, M.; Arabshahi, H. J.; Jovanović, K.; Richter, K. W.; Cazacu, M.; Shova, S.; Balan, M.; Andersen, N. H.; Radulović, S.; Reynisson, J.; Andersson, K. K.; Arion, V. B. New iminodiacetate–thiosemicarbazone hybrids and their copper(Ⅱ) complexes are potential ribonucleotide reductase R₂ inhibitors with high antiproliferative activity. Inorg. Chem. 2017, 56, 3532–3549. doi: 10.1021/acs.inorgchem.6b03178
5. [5]
  Pal, I.; Basuli, F.; Mak, T. C. W.; Bhattacharya, S. Synthesis, structure, and properties of a novel heterooctametallic complex containing a cyclic Ru₄Ni₄ core. Angew. Chem., Int. Ed. 2001, 40, 2923–2925. doi: 10.1002/1521-3773(20010803)40:15<2923::AID-ANIE2923>3.0.CO;2-J
6. [6]
  Demoro, B.; Sarniguet, C.; Sánchez-Delgado, R.; Rossi, M.; Liebowitz, D.; Caruso, F.; Olea-Azar, C.; Moreno, V.; Medeiros, A.; Comini, M. A.; Otero, L.; Gambino, D. New organoruthenium complexes with bioactive thiosemicarbazones as co-ligands: potential anti-trypanosomal agents. Dalton Trans. 2012, 41, 1534–1543. doi: 10.1039/C1DT11519G
7. [7]
  Adams, M.; Khot, Y.; Li, H.; De Kock, C.; Smith; P. J.; Land, K.; Chibalea, K.; Smith, G. S. The synthesis and antiparasitic activity of aryl- and ferrocenyl-derived thiosemicarbazone Ruthenium(Ⅱ)–arene complexes. Dalton Trans. 2013, 42, 4677–4685. doi: 10.1039/c3dt32740j
8. [8]
  Stacy, A. E.; Palanimuthu, D.; Bernhardt, P. V.; Kalinowski, D. S.; Jansson, P. J.; Richardson, D. R. Zinc(Ⅱ)-thiosemicarbazone complexes are localized to the lysosomal compartment where they transmetallate with copper ions to induce cytotoxicity. J. Med. Chem. 2016, 59, 4965–4984. doi: 10.1021/acs.jmedchem.6b00238
9. [9]
  Oliveira, Alexandre. A.; Perdigão, G. M. C.; Rodrigues, L. E.; da Silva, J. G.; Souza-Fagundes, E. M.; Takahashi, J. A.; Rocha, W. R.; Beraldo, H. Cytotoxic and antimicrobial effects of Indium(Ⅲ) complexes with 2-acetylpyridine-derived thiosemicarbazones. Dalton Trans. 2017, 46, 918-932. doi: 10.1039/C6DT03657K
10. [10]
  King, A. P.; Gellineau, H. A.; Ahn, J. E.; MacMillan, S. N.; Wilson, J. J. Bis(thiosemicarbazone) complexes of cobalt(Ⅲ). synthesis, characterization, and anticancer potential. Inorg. Chem. 2017, 56, 6609–6623. doi: 10.1021/acs.inorgchem.7b00710
11. [11]
  Medici, S.; Peana, M.; Nurchi, V. M.; Lachowicz, J. I.; Crisponi, G.; Zoroddu, M. A. Noble metals in medicine: latest advances. Coord. Chem. Rev. 2015, 284, 329-350. doi: 10.1016/j.ccr.2014.08.002
12. [12]
  Murray, B. S.; Babak, M. V.; Hartinger, C. G.; Dyson, P. J. The development of RAPTA compounds for the treatment of tumors. Coord. Chem. Rev. 2016, 306, 86–114. doi: 10.1016/j.ccr.2015.06.014
13. [13]
  Su, W.; Tang, Z.; Li, P. Development of arene Ruthenium antitumor complexes. Mini-Rev. Med. Chem. 2016, 16, 787-795. doi: 10.2174/138955751610160503003937
14. [14]
  Zhao, J.; Li, S.; Wang, X.; Xu, G.; Gou, S. Dinuclear organoruthenium complexes exhibiting antiproliferative activity through DNA damage and a reactive-oxygen-speciesMediated endoplasmic reticulum stress pathway. Inorg. Chem. 2019, 58, 2208-2217. doi: 10.1021/acs.inorgchem.8b03447
15. [15]
  Acharya, S.; Maji, M.; Ruturaj.; Purkait, K.; Gupta, A.; Mukherjee, A. Synthesis, structure, stability, and inhibition of tubulin polymerization by Ru(Ⅱ)−p‑cymene complexes of trimethoxyaniline based schiff bases. Inorg. Chem. 2019, 58, 9213−9224. doi: 10.1021/acs.inorgchem.9b00853
16. [16]
  Morris, R. E.; Aird, R. E.; Murdoch, P. del S.; Chen, H.; Cummings, J.; Hughes, N. D.; Parsons, S.; Parkin, A.; Boyd, G.; Jodrell, D. I.; Sadler, P. J. Inhibition of cancer cell growth by Ruthenium(Ⅱ) arene complexes. J. Med. Chem. 2001, 44, 3616-3621. doi: 10.1021/jm010051m
17. [17]
  Scolaro, C.; Bergamo, A, ; Brescacin, L.; Delfino, R.; Cocchietto, M.; Laurenczy, G.; Geldbach, T. J.; Sava, G.; Dyson, P. J. In vitro and in vivo evaluation of Ruthenium(Ⅱ)-arene PTA complexes. J. Med. Chem. 2005, 48, 4161–4171. doi: 10.1021/jm050015d
18. [18]
  Meng, T.; Qin, Q. P.; Chen, Z. L.; Zou, H. H.; Wang, K.; Liang, F. P. Development of arene Ruthenium antitumor complexes. Dalton Trans. 2019, 48, 5352-5360. doi: 10.1039/C9DT00866G
19. [19]
  Beckford, F.; Dourth, D.; Shaloski Jr, M.; Didion, J.; Thessing, J.; Woods, J.; Crowell, V.; Gerasimchuk, N.; Gonzalez-Sarrías, A.; Seeram, N. P. Dinuclear organoruthenium complexes exhibiting antiproliferative activity through DNA damage and a reactive-oxygen-speciesMediated endoplasmic reticulum stress pathway. J. Inorg. Biochem. 2011, 105, 1019–1029. doi: 10.1016/j.jinorgbio.2011.04.008
20. [20]
  Adams, M.; Li, Y.; Khot, H.; De Kock, C.; Smith, P. J.; Land, K.; Chibalea, K.; Smith, G. S. The synthesis and antiparasitic activity of aryl- and ferrocenyl-derived thiosemicarbazone ruthenium(Ⅱ)–arene complexes. Dalton Trans. 2013, 42, 4677–4685. doi: 10.1039/c3dt32740j
21. [21]
  Su, W.; Qian, Q.; Li, P.; Lei, X.; Xiao, Q.; Huang, S.; Huang, C.; Cui, J. Synthesis, characterization and anticancer activity of a series of curcuminoids and their half-sandwich ruthenium(Ⅱ) complexes. Inorg. Chem., 2013, 52, 12440–12449. doi: 10.1021/ic401362s
22. [22]
  Su, W.; Tang, Z.; Xiao, Q.; Li, P.; Qian, Q.; Lei, X.; Huang, S.; Peng, B.; Cui, J.; Huang, C. Synthesis, characterization, and anticancer activity of a series of ketone‑N₄‑substituted thiosemicarbazones and their Ruthenium(Ⅱ) arene complexes. J. Organometal. Chem. 2015, 783, 10–16. doi: 10.1016/j.jorganchem.2014.12.041
23. [23]
  Gatti, A.; Habtemariam, A.; Romero-Canelon, I.; Song, J. I.; Heer, Bindy.; Clarkson, G. J.; Rogolino, D.; Sadler, P. J.; Carcelli, M. Half-sandwich arene Ruthenium(Ⅱ) and Osmium(Ⅱ) thiosemicarbazone complexes: Solution behavior and antiproliferative activity. Organometallics, 2018, 37, 891-899. doi: 10.1021/acs.organomet.7b00875
24. [24]
  Demoro, B.; Sarniguet, C.; Sanchez-Delgado, R.; Rossi, M.; Liebowitz, D.; Caruso, F.; Olea-Azar, C.; Moreno, V.; Medeiros, A.; Comini, M. A.; Otero, L.; Gambino, D. New organoruthenium complexes with bioactive thiosemicarbazones as co-ligands: potential anti-trypanosomal agents. Dalton Trans. 2012, 41, 1534–1543. doi: 10.1039/C1DT11519G
25. [25]
  Demoro, B.; de Almeida, R. F. M.; Marques, F.; Matos, C. P. L.; Otero.; Pessoa, J. C.; Santos, I.; Rodríguez, A.; Moreno, V.; Lorenzo, J.; Gambino, D.; Toma, A. I. Screening organometallic binuclear thiosemicarbazone ruthenium complexes as potential anti-tumour agents: cytotoxic activity and human serum albumin binding mechanism. Dalton Trans. 2013, 42, 7131–7146. doi: 10.1039/c3dt00028a
26. [26]
  Su, W.; Tang, Z.; Li, P.; Wang, G.; Xiao, Q.; Li, Y.; Huang, S.; Gu, Y.; Lai, Z.; Zhang, Y. New dinuclear ruthenium arene complexes containing thiosemicarbazone ligands: synthesis, structure and cytotoxic studies. Dalton Trans. 2016, 45, 19329–19340. doi: 10.1039/C6DT03306G
27. [27]
  SAINT Software Reference Manual, Bruker AXS, Madison, WI, 1998.
28. [28]
  Sheldrick, G. M. Phase annealing in SHELX-90: direct methods for larger structures. Acta Crystallogr. Sect. 1990, A46, 467.
29. [29]
  Sheldrick, G. M. SHELXS-97, Program for X-ray Crystal Structure Solution, University of Göttingen, Göttingen, Germany, 1997.
30. [30]
  Crystal data for 2. formula (C₄₀H₅₂N₆O₂P₂F₁₂Ru₂S₂), M_r = 1205.0785, crystal sysem: trigonal; space group: R-3; a = 34.752(3) Å, b = 34.752(3) Å, c = 11.9575(13) Å; α = 90.00°, β = 90.00°, γ = 120.00°; V = 12506(2) Å³; Z = 18, D_c = 1.402 Mg/m³, μ = 0.748 mm^‑1; F(000) = 5328; R_int = 0.0464, reflns collected = 20071, reflns ind = 5061, GOOF (S) = 1.063; final R indices (I ≥ 2σ (I)) R1 ₌ 0.0668, wR2 = 0.2005; final R indices (all data) R1₌0.0904, wR2 = 0.2144.
31. [31]
  Frisch, M. J. T. G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A. Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, N. J.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision A. 1Wallingford CT; 2009
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