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Transition Metal Chemistry

, Volume 43, Issue 2, pp 171–183 | Cite as

Oxovanadium phenanthroimidazole derivatives: synthesis, DNA binding and antitumor activities

  • Yin-Liang Bai
  • Ya-Wu Zhang
  • Ji-Yuan Xiao
  • Hai-Wei Guo
  • Xiang-Wen Liao
  • Wen-Jie Li
  • You-Cheng Zhang
Article
  • 94 Downloads

Abstract

Four unsymmetrical oxovanadium phenanthroimidazole complexes, [VO(hntdtsc)(NPIP)] (1), [VO(hntdtsc)(CPIP)] (2), [VO(hntdtsc)(MEPIP)] (3) and [VO(hntdtsc)(HPIP)] (4) (hntdtsc = 2-hydroxy-1-naphthaldehyde thiosemicarbazone, NPIP = 2-(4-nitrophenyl)-imidazo[4,5-f]1,10-phenanthroline, CPIP = 2-(4-chlorphenyl)-imidazo[4,5-f]1,10-phenanthroline), MEPIP = 2-(4-methylphenyl)-imidazo[4,5-f]1,10-phenanthroline), HPIP = 2-(4-hydroxylphenyl)-imidazo[4,5-f] 1,10-phenanthroline), have been synthesized and characterized. Their DNA binding and antitumor activities were determined by biochemical methods. All four oxovanadium complexes can bind with CT-DNA by an intercalation model and can also cleave supercoiled plasmid DNA in the presence of H2O2. The antitumor properties and mechanism of the complexes have been analyzed by MTT assay, cell cycle analysis, apoptosis assay and Western blot analysis. The results showed that the free ligands and their corresponding complexes all possess antiproliferative activities with very low IC50 values against Hela, BIU-87 and SPC-A-1 cell lines. Complex 1, which has a strongly electron-withdrawing nitro group, exhibited the best antiproliferative activities. Complex 1 caused G0/G1 phase arrest of the cell cycle and induced apoptosis in Hela cells. Additionally, complex 1 attenuated the phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2).This indicates that inhibition of the ERK1/2 signaling pathway may contribute to the antitumor effects of these complexes.

Notes

Acknowledgements

This study was supported by Natural Science Foundation of Gansu Province, China (Grant No. 145RJZA143) and Administration of traditional Chinese medicine Scientific Research Funds of Gansu Province (Grant No. GZK-2017-53). We thank Dr. Zhi-Jian Han for language editing and improvement.

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Yin-Liang Bai
    • 1
  • Ya-Wu Zhang
    • 2
  • Ji-Yuan Xiao
    • 1
  • Hai-Wei Guo
    • 3
  • Xiang-Wen Liao
    • 3
  • Wen-Jie Li
    • 4
  • You-Cheng Zhang
    • 2
  1. 1.Department of PharmacyLanzhou University Second HospitalLanzhouChina
  2. 2.Department of General SurgeryLanzhou University Second HospitalLanzhouChina
  3. 3.School of PharmacyGuangdong Pharmaceutical UniversityGuangzhouChina
  4. 4.Department of Clinical Pharmacology, School of Pharmaceutical SciencesZhengzhou UniversityZhengzhouChina

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