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.
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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.
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Bai, YL., Zhang, YW., Xiao, JY. et al. Oxovanadium phenanthroimidazole derivatives: synthesis, DNA binding and antitumor activities. Transit Met Chem 43, 171–183 (2018). https://doi.org/10.1007/s11243-018-0205-9
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DOI: https://doi.org/10.1007/s11243-018-0205-9