Citation: Shi-Fang JIA, Xiu-Li HAO, Yan-Zhen WEN, Yan ZHANG. Synthesis, Characterization, and Antitumor Activity of Ruthenium(Ⅱ) Complexes Based on Schiff Base Ligand[J]. Chinese Journal of Inorganic Chemistry, ;2022, 38(10): 1919-1926. doi: 10.11862/CJIC.2022.191 shu

Synthesis, Characterization, and Antitumor Activity of Ruthenium(Ⅱ) Complexes Based on Schiff Base Ligand

School of Chemical and Biological Engineering, Taiyuan Science and Technology University, Taiyuan 030021, China

Corresponding author: Yan ZHANG, yanzhang872010@163.com
Received Date: 25 November 2021
Revised Date: 6 June 2022

Figures(7)

A series of new Schiff base ligands (BLⁿ, n=1 - 3) and complexes have been synthesized. Binuclear ruthenium complexes [Ru(BLⁿ)(bpy)₂]₂(ClO₄)₄, where bpy=2, 2'-bipyridine, BLⁿ=((PyCHN)-Ph-O-C₆H₄) ₂R (PyCHN=N-2-pyridylmethylene, R=none for Ru1, —C(CH₃)₂ for Ru2 and —SO₂ for Ru3), have been prepared and characterized by element analysis, ¹H NMR, IR, and mass spectrometry methods. The cytotoxicity to cervical cancer cells (Hela), gastric cancer cells (BGC823), gastric cancer cells (SGC-7901), and human normal embryonic lung fibroblasts cells (MRC-5) of the three complexes in vitro was evaluated using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. It is worth noting that Ru1-Ru3 showed excellent antitumor effects in a cellular study for BGC823 in vitro. However, Ru3 exhibited the highest cytotoxicity to any cancer cells than Ru1 and Ru2.
- Schiff base ligand,
- binuclear ruthenium complexes,
- cytotoxicity
1. [1]
  Rosenberg B, Vancamp L. Platinum Compounds: A New Class of Potent Antitumour Agents[J]. Nature, 1969,222:385-386. doi: 10.1038/222385a0
2. [2]
  Esref Alkis M, Kelestemür Ü, Alan Y, Turan N, Buldurun K. Cobalt and Ruthenium Complexes with Pyrimidine Based Schiff Base: Synthesis, Characterization, Anticancer Activities and Electrochemotherapy Efficiency[J]. J. Mol. Struct., 2021,1226129402. doi: 10.1016/j.molstruc.2020.129402
3. [3]
  Jiang G B, Zhang W Y, He M, Gu Y Y, Bai L, Wang Y J, Qiao Y, Du F. Anticancer Activity of Two Ruthenium (Ⅱ) Polypyridyl Complexes toward Hepatocellular Carcinoma HepG - 2 Cells[J]. Polyhedron, 2019,169:209-218. doi: 10.1016/j.poly.2019.05.017
4. [4]
  Małecka M, Skoczynska A, Goodman D M, Hartinger C G, Budzisz E. Biological Properties of Ruthenium (Ⅱ)/(Ⅲ) Complexes with Flavonoids as Ligands[J]. Coord. Chem. Rev., 2021,436213849. doi: 10.1016/j.ccr.2021.213849
5. [5]
  Jiang G B, Zhang W Y, He M, Gu Y Y, Bai L, Wang Y J, Yi Q Y, Du F. Systematic Evaluation of the Antitumor Activity of Three Ruthenium Polypyridyl Complexes[J]. J. Inorg. Biochem., 2021,225111616. doi: 10.1016/j.jinorgbio.2021.111616
6. [6]
  Savić A, Gligorijević N, Aranđelović S. Antitumor Activity of Organoruthenium Complexes with Chelate Aromatic Ligands, Derived from 1, 10 - Phenantroline: Synthesis and Biological Activity[J]. J. Inorg. Biochem., 2020,202110869. doi: 10.1016/j.jinorgbio.2019.110869
7. [7]
  Jana D, Zhao Y L. Strategies for Enhancing Cancer Chemodynamic Therapy Performance[J]. Exploration, 2022(2)20210238.
8. [8]
  Hartinger C G, Jakupeca M A, Zorbas S, Groessl M, Egger A, Berger W, Zorbas H, Dyson P J, Keppler B K. KP1019, A New Redox-Active Anticancer Agent-Preclinical Development and Results of a Clinical Phase Ⅰ Study in Tumor Patients[J]. Chem. Biodivers., 2008,5(10):2140-2155. doi: 10.1002/cbdv.200890195
9. [9]
  Leigen S, Burgers S A, Baas P, Pluim D, Tibben M, Werkhoven E, Alessio E, Sava G, Beijnen J H, Schellens J H M. Phase Ⅰ/Ⅱ Study with Ruthenium Compound NAMI - A and Gemcitabine in Patients with Non - small Cell Lung Cancer after First Line Therapy[J]. Invest. New Drugs, 2015,33(1):201-214. doi: 10.1007/s10637-014-0179-1
10. [10]
  Schatzschneider U, Niesel J, Ott I, Gust R, Alborzinia H, Wölfl S. Cellular Uptake, Cytotoxicity, and Metabolic Profiling of Human Cancer Cells Treated with Ruthenium (Ⅱ) Polypyridyl Complexes[J]. ChemMedChem, 2008,3(7):1104-1109. doi: 10.1002/cmdc.200800039
11. [11]
  Lentz F, Drescher A, Lindauer A, Henke M, Hilger R A, Hartinger C G, Scheulen M E, Dittrich C, Keppler B K, Jaehde U. Pharmacokinetics of a Novel Anticancer Ruthenium Complex (KP1019, FFC14A) in a Phase Ⅰ Dose-Escalation Study[J]. Anti-Cancer Drugs, 2009,20(2):97-103. doi: 10.1097/CAD.0b013e328322fbc5
12. [12]
  Zhong Y W, Wu S H, Burkhardt S E, Yao C J, Abruña H D. Mononuclear and Dinuclear Ruthenium Complexes of 2, 3-Di-2-pyridyl-5, 6-diphenylpyrazine: Synthesis and Spectroscopic and Electrochemical Studies[J]. Inorg. Chem., 2011,50(2):517-524. doi: 10.1021/ic101629w
13. [13]
  Huang W K, Cheng C W, Chang S M, Lee Y P, Eric W G. Synthesis and Electron - Transfer Properties of Benzimidazole - Functionalized Ruthenium Complexes for Highly Efficient Dye - Sensitized Solar Cells[J]. Chem. Commun., 2010,46(47):8992-8994. doi: 10.1039/c0cc03517c
14. [14]
  Garza-Ortiz A, Maheswari P U, Lutz M, Siegler M A, Reedijk J. Tuning the Cytotoxic Properties of New Ruthenium(Ⅲ) and Ruthenium(Ⅱ) Complexes with a Modified Bis(arylimino)pyridine Schiff Base Ligand Using Bidentate Pyridine - Based Ligands[J]. J. Biol. Inorg. Chem., 2014,19:675-689. doi: 10.1007/s00775-013-1083-4
15. [15]
  Selvamurugan S, Viswanathamurthi P, Endo A, Hashimoto T, Natarajan K. Synthesis, Spectral Characterization, Antioxidant, Anticancer In Vitro, and DNA Cleavage Studies of a Series of Ruthenium (Ⅱ) Complexes Bearing Schiff Base Ligands[J]. J. Coord. Chem., 2013,66(22):4052-4066. doi: 10.1080/00958972.2013.858135
16. [16]
  Sathiyaraj S, Sampath K, Butcher R J. Designing, Structural Elucidation, Comparison of DNA Binding, Cleavage, Radical Scavenging Activity and Anticancer Activity of Copper (Ⅰ) Complex with 5-Dimethyl-2-phenyl-4-[(pyridin-2-ylmethylene)-amino]-1, 2-dihydropyrazol-3-one Schiff Base Ligand[J]. Eur. J. Med. Chem., 2013,64:81-89. doi: 10.1016/j.ejmech.2013.03.047
17. [17]
  Garza-Ortiz A, Maheswari P U, Siegler M, Spek A L, Reedijk J. A New Family of Ru (Ⅱ) Complexes with a Tridentate Pyridine Schiff-Base Ligand and Bidentate Co-ligands: Synthesis, Characterization, Structure and In Vitro Cytotoxicity Studies[J]. New J. Chem., 2013,37:3450-3460. doi: 10.1039/c3nj00415e
18. [18]
  Sathiyaraj S, Butcher R J, Jayabalakrishnan C. Synthesis, Characterization, DNA Interaction and In Vitro Cytotoxicity Activities of Ruthenium(Ⅱ) Schiff Base Complexes[J]. J. Mol. Struct., 2012,1030:95-103. doi: 10.1016/j.molstruc.2012.07.021
19. [19]
  Raja G, Butcher R J, Jayabalakrishnan C. Studies on Synthesis, Characterization, DNA Interaction and Cytotoxicity of Ruthenium(Ⅱ) Schiff Base Complexes[J]. Spectroc. Acta Pt. A-Molec. Biomolec. Spectr., 2012,94:210-215. doi: 10.1016/j.saa.2012.03.035
20. [20]
  Mosmann T. Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays[J]. J. Immunol. Methods, 1983,65(1/2):55-63.
21. [21]
  BAI X F, MA X, XIE X X, SHAO M S, GUO N N, YAN N, YAO L. Synthesis and Anti-tumor Activity of Tubulysins Analogues[J]. Chem. J. Chinese Universities, 2017,38(1):47-55.
22. [22]
  Zhang Y, Cai P, Hu P C, Yang F, Cheng G Z. Synthesis, Characterization, Crystal Structure, Cytotoxicity, Apoptosis and Cell Cycle Arrest of Ruthenium (Ⅱ) Complex[Ru(bpy)₂(adpa)] (PF₆)₂ (bpy=2, 2'-Bipyridine, adpa=4-(4-Aminophenyl) diazenyl-N-(pyridin-2-ylmethylene)aniline)[J]. RSC Adv., 2015,5:11591-11598. doi: 10.1039/C4RA12715C
23. [23]
  Mendoza-Ferri M G, Hartinger C G, Mendoza M A, Groessl M, Egger A E, Eichinger R E, Mangrum J B, Farrell N P, Maruszak M, Bednarski P J, Klein F, Jakupec M A, Nazarov A A, Severin K, Keppler B K. Transferring the Concept of Multinuclearity to Ruthenium Complexes for Improvement of Anticancer Activity[J]. J. Med. Chem., 2009,52:916-925. doi: 10.1021/jm8013234
24. [24]
  Giannini F, Paul L E H, Furrer J, Therrien B, Süss-Fink G. Highly Cytotoxic Diruthenium Trithiolato Complexes of the Type[(η⁶-p-MeC₆H₄Prⁱ)₂Ru₂(μ₂ - SR)₃]⁺ : Synthesis, Characterization, Molecular Structure and In Vitro Anticancer Activity[J]. New J. Chem., 2013,37:3503-3511. doi: 10.1039/c3nj00476g
25. [25]
  Mulyana Y, Weber D K, Buck D P, Motti C A, Collinsb J G, Keene F R. Oligonuclear Polypyridylruthenium (Ⅱ) Complexes Incorporating Flexible Polar and Non-polar Bridges: Synthesis, DNA-Binding and Cytotoxicity[J]. Dalton Trans., 2011,40:1510-1523. doi: 10.1039/c0dt01250e
26. [26]
  Gorle A K, Ammit A J, Wallace L, Keene F R, Collins J G. Multinuclear Ruthenium(Ⅱ) Complexes as Anticancer Agents[J]. New J. Chem., 2014,38:4049-4059. doi: 10.1039/C4NJ00545G
27. [27]
  DeBerardinis R J, Lum J J, Hatzivassiliou G, Thompson C B. The Biology of Cancer: Metabolic Reprogramming Fuels Cell Growth and Proliferation[J]. Cell Metab., 2008,7(1):11-20. doi: 10.1016/j.cmet.2007.10.002
28. [28]
  Liu H Y, Yuan Y Z, Guo H Y, Mitchelson K, Zhang K, Xie L, Qin W Y, Lu Y, Wang J, Guo Y, Zhou Y X, He F C. Hepatitis B Virus Encoded X Protein Suppresses Apoptosis by Inhibition of the Caspase-Independent Pathway[J]. J. Proteome Res., 2012,11(10):4803-4813. doi: 10.1021/pr2012297
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