New Oxidovanadium Complexes Incorporating Thiosemicarbazones and 1, 10‐Phenanthroline Derivatives as DNA Cleavage, Potential Anticancer Agents, and Hydroxyl Radical Scavenger

Abstract

Four novel oxidovanadium(IV) complexes, [VO(hntdtsc)(PHIP)] (1) (hntdtsc = 2-hydroxy-1-naphthaldehyde thiosemicarbazone, PHIP= 2-phenyl-imidazo[4,5-f]1,10-phenanthroline), [VO(hntdtsc)(DPPZ)](2)(DPPZ= dipyrido[3,2-a:2',3'-c]phenazine), [VO(satsc)(PHIP)](3) (satsc=salicylaldehyde thiosemicarbazone), and [VO(satsc)(DPPZ)](4), have been prepared and characterized. The chemical nuclease activities and photocleavage reactions of the complexes were tested. All four complexes can efficiently cleave pBR322 DNA, and complex 1 has the best cleaving ability. The antitumor properties of these complexes were examined with three different tumor cell lines using MTT assay. Their antitumor mechanism has been analyzed using cell cycle analysis, fluorescence microscopy of apoptosis, and Annexin V-FITC/PI assay. The results showed that the growth of human neuroblastoma (SH-SY5Y, SK-N-SH) and human breast adenocarcinoma (MCF-7) cells were inhibited significantly with very low IC50 values. Complex 1 was found to be the most potent antitumor agent among the four complexes. It can cause G0/G1 phase arrest of the cell cycle and exhibited significant induced apoptosis in SK-N-SH cells and displayed typical morphological apoptotic characteristics. In addition, they all displayed reasonable abilities to scavenge hydroxyl radical, and complex 1 was the best inhibitor.

Molecular and Cellular Mechanisms of Cytotoxic Activity of Vanadium Compounds against Cancer Cells

“…Contrary to this study, other phenanthroline-based vanadium complex (73 and 74) caused a G0/G1 phase cell cycle arrest in the same type of cancer cell lines [82]. Additionally, G0/G1 phase cell cycle arrest, induced by organic vanadium complexes (75)(76)(77)(78), was shown in human neuroblastoma cells [83]. Cell cycle arrest in S phase has been determined in esophageal squamous carcinoma cell lines treated by sodium vanadate (61) [84].…”

Synthesis of New Oxido-Vanadium Complexes: Catalytic Properties and Cytotoxicity

“…A number of vanadium(IV) and vanadium(V) complexes with N,O donor ligands have been examined for potential medicinal applications. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] The anticancer activity of a few oxido-vanadium(IV) complexes encouraged us to prepare new oxido-vanadium(IV) complexes incorporating N,O donor ligands with reversible electron transfer properties. This work stems from our interest in the vanadium chemistry of azosalen ligands.…”

Vanadium(IV/V) complexes of Triapine and related thiosemicarbazones: Synthesis, solution equilibrium and bioactivity

“…formed between pH ~3 and ~11, our data suggest ligand coordination most probably via the antiproliferative activity [39] compared to the class of α(N)-pyridyl TSCs [7]. This can probably be explained by the fact that α(N)-pyridyl TSCs were found to be unambiguously more efficient chelators for Fe(II) than STSC over a wide pH range [25].…”