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
1. [1]
  Haitang WANG , Yanni LING , Xiaqing MA , Yuxin CHEN , Rui ZHANG , Keyi WANG , Ying ZHANG , Wenmin WANG . Construction, crystal structures, and biological activities of two Ln^Ⅲ₃ complexes. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1474-1482. doi: 10.11862/CJIC.20240188
2. [2]
  Jing WU , Puzhen HUI , Huilin ZHENG , Pingchuan YUAN , Chunfei WANG , Hui WANG , Xiaoxia GU . Synthesis, crystal structures, and antitumor activities of transition metal complexes incorporating a naphthol-aldehyde Schiff base ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2422-2428. doi: 10.11862/CJIC.20240278
3. [3]
  Xin MA , Ya SUN , Na SUN , Qian KANG , Jiajia ZHANG , Ruitao ZHU , Xiaoli GAO . A Tb₂ complex based on polydentate Schiff base: Crystal structure, fluorescence properties, and biological activity. Chinese Journal of Inorganic Chemistry, 2024, 40(7): 1347-1356. doi: 10.11862/CJIC.20230357
4. [4]
  Jing JIN , Zhuming GUO , Zhiyin XIAO , Xiujuan JIANG , Yi HE , Xiaoming LIU . Tuning the stability and cytotoxicity of fac-[Fe(CO)₃I₃]^- anion by its counter ions: From aminiums to inorganic cations. Chinese Journal of Inorganic Chemistry, 2024, 40(5): 991-1004. doi: 10.11862/CJIC.20230458
5. [5]
  Yinling HOU , Jia JI , Hong YU , Xiaoyun BIAN , Xiaofen GUAN , Jing QIU , Shuyi REN , Ming FANG . A rhombic Dy₄-based complex showing remarkable single-molecule magnet behavior. Chinese Journal of Inorganic Chemistry, 2025, 41(3): 605-612. doi: 10.11862/CJIC.20240251
6. [6]
  Linjie ZHU , Xufeng LIU . Electrocatalytic hydrogen evolution performance of tetra-iron complexes with bridging diphosphine ligands. Chinese Journal of Inorganic Chemistry, 2025, 41(2): 321-328. doi: 10.11862/CJIC.20240207
7. [7]
  Yingchun ZHANG , Yiwei SHI , Ruijie YANG , Xin WANG , Zhiguo SONG , Min WANG . Dual ligands manganese complexes based on benzene sulfonic acid and 2, 2′-bipyridine: Structure and catalytic properties and mechanism in Mannich reaction. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1501-1510. doi: 10.11862/CJIC.20240078
8. [8]
  Jinlong YAN , Weina WU , Yuan WANG . A simple Schiff base probe for the fluorescent turn-on detection of hypochlorite and its biological imaging application. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1653-1660. doi: 10.11862/CJIC.20240154
9. [9]
  Yanyang Li , Zongpei Zhang , Kai Li , Shuangquan Zang . Ideological and Political Design for the Comprehensive Experiment of the Synthesis and Aggregation-Induced Emission (AIE) Performance Study of Salicylaldehyde Schiff-Base. University Chemistry, 2024, 39(2): 105-109. doi: 10.3866/PKU.DXHX202307020
10. [10]
  Yongpo Zhang , Xinfeng Li , Yafei Song , Mengyao Sun , Congcong Yin , Chunyan Gao , Jinzhong Zhao . Synthesis of Chlorine-Bridged Binuclear Cu(I) Complexes Based on Conjugation-Driven Cu(II) Oxidized Secondary Amines. University Chemistry, 2024, 39(5): 44-51. doi: 10.3866/PKU.DXHX202309092
11. [11]
  Ke QIAO , Yanlin LI , Shengli HUANG , Guoyu YANG . Advancements in asymmetric catalysis employing chiral iridium (ruthenium) complexes. Chinese Journal of Inorganic Chemistry, 2024, 40(11): 2091-2104. doi: 10.11862/CJIC.20240265
12. [12]
  Qilu DU , Li ZHAO , Peng NIE , Bo XU . Synthesis and characterization of osmium-germyl complexes stabilized by triphenyl ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1088-1094. doi: 10.11862/CJIC.20240006
13. [13]
  Cheng Zheng , Shiying Zheng , Yanping Zhang , Shoutian Zheng , Qiaohua Wei . Synthesis, Copper Content Analysis, and Luminescent Performance Study of Binuclear Copper (I) Complexes with Isomeric Luminescence Shift: A Comprehensive Chemical Experiment Recommendation. University Chemistry, 2024, 39(7): 322-329. doi: 10.3866/PKU.DXHX202310131
14. [14]
  Hong RAO , Yang HU , Yicong MA , Chunxin LÜ , Wei ZHONG , Lihua DU . Synthesis and in vitro anticancer activity of phenanthroline-functionalized nitrogen heterocyclic carbene homo- and heterobimetallic silver/gold complexes. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2429-2437. doi: 10.11862/CJIC.20240275
15. [15]
  Jinfeng Chu , Yicheng Wang , Ji Qi , Yulin Liu , Yan Li , Lan Jin , Lei He , Yufei Song . Comprehensive Chemical Experiment Design: Convenient Preparation and Characterization of an Oxygen-Bridged Trinuclear Iron(III) Complex. University Chemistry, 2024, 39(7): 299-306. doi: 10.3866/PKU.DXHX202310105
16. [16]
  Changqing MIAO , Fengjiao CHEN , Wenyu LI , Shujie WEI , Yuqing YAO , Keyi WANG , Ni WANG , Xiaoyan XIN , Ming FANG . Crystal structures, DNA action, and antibacterial activities of three tetranuclear lanthanide-based complexes. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2455-2465. doi: 10.11862/CJIC.20240192
17. [17]
  Zhongxin YU , Wei SONG , Yang LIU , Yuxue DING , Fanhao MENG , Shuju WANG , Lixin YOU . Fluorescence sensing on chlortetracycline of a Zn-coordination polymer based on mixed ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2415-2421. doi: 10.11862/CJIC.20240304
18. [18]
  Lubing Qin , Fang Sun , Meiyin Li , Hao Fan , Likai Wang , Qing Tang , Chundong Wang , Zhenghua Tang . 原子精确的(AgPd)₂₇团簇用于硝酸盐电还原制氨：一种配体诱导策略来调控金属核. Acta Physico-Chimica Sinica, 2025, 41(1): 2403008-. doi: 10.3866/PKU.WHXB202403008
19. [19]
  Xiao SANG , Qi LIU , Jianping LANG . Synthesis, structure, and fluorescence properties of Zn(Ⅱ) coordination polymers containing tetra-alkenylpyridine ligands. Chinese Journal of Inorganic Chemistry, 2024, 40(11): 2124-2132. doi: 10.11862/CJIC.20240158
20. [20]
  Xiaowei TANG , Shiquan XIAO , Jingwen SUN , Yu ZHU , Xiaoting CHEN , Haiyan ZHANG . A zinc complex for the detection of anthrax biomarker. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1850-1860. doi: 10.11862/CJIC.20240173

Get Citation

PDF

XML

Metrics

PDF Downloads(8)
Abstract views(846)
HTML views(236)

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