Oxovanadium phenanthroimidazole derivatives: synthesis, DNA binding and antitumor activities

• Published in: Transition metal chemistry (Weinheim) Vol. 43; no. 2; pp. 171 - 183
• Main Authors: Bai, Yin-Liang, Zhang, Ya-Wu, Xiao, Ji-Yuan, Guo, Hai-Wei, Liao, Xiang-Wen, Li, Wen-Jie, Zhang, You-Cheng
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.03.2018; Springer Nature B.V
• Subjects: Anticancer properties; Apoptosis; Binding; Catalysis; Cell cycle; Chemistry; Chemistry and Materials Science; Coordination compounds; Deoxyribonucleic acid; DNA; Hydrogen peroxide; Inorganic Chemistry; Kinases; Organometallic Chemistry; Phosphorylation; Physical Chemistry; Plasmids; Signaling
• ISSN: 0340-4285; 1572-901X
• DOI: 10.1007/s11243-018-0205-9

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 H 2 O 2 . 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 IC 50 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 G 0 /G 1 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.