Exploring the Antitumor Efficacy of N-Heterocyclic Nitrilotriacetate Oxidovanadium(IV) Salts on Prostate and Breast Cancer Cells.

The crystal structures of two newly synthesized nitrilotriacetate oxidovanadium(IV) salts, namely [QH][VO(nta)(H 2 O)](H 2 O) 2 ( I ) and [(acr)H][VO(nta)(H 2 O)](H 2 O) 2 ( II ), were determined. Additionally, the cytotoxic effects of four N-heterocyclic nitrilotriacetate oxidovanadium(IV) salts-1,10-phenanthrolinium, [(phen)H][VO(nta)(H 2 O)](H 2 O) 0.5 ( III ), 2,2'-bipyridinium [(bpy)H][VO(nta)(H 2 O)](H 2 O) ( IV ), and two newly synthesized compounds ( I ) and ( II )-were evaluated against prostate cancer (PC3) and breast cancer (MCF-7) cells. All the compounds exhibited strong cytotoxic effects on cancer cells and normal cells (HaCaT human keratinocytes). The structure-activity relationship analysis revealed that the number and arrangement of conjugated aromatic rings in the counterion had an impact on the antitumor effect. The compound (III), the 1,10-phenanthrolinium analogue, exhibited the greatest activity, whereas the acridinium salt (II), with a different arrangement of three conjugated aromatic rings, showed the lowest toxicity. The increased concentrations of the compounds resulted in alterations to the cell cycle distribution with different effects in MCF-7 and PC3 cells. In MCF-7 cells, compounds I and II were observed to block the G 2 /M phase, while compounds III and IV were found to arrest the cell cycle in the G 0 /G 1 phase. In PC3 cells, all compounds increased the rates of cells in the G 0 /G 1 phase.