The antitumor activity of zinc(II) and copper(II) complexes with 5,7-dihalo-substituted-8-quinolinoline

Abstract

[Zn₂(ClQ)₄(CH₃OH)₂] (1), [Zn(BrQ)₂(H₂O)₂] (2), [Zn₂(ClIQ)₄] (3) and [Cu(BrQ)₂] (4) (H-ClQ = 5,7-dichloro-8-hydroxylquinoline, H-BrQ = 5,7-dibromo-8-hydroxylquinoline, and H-ClIQ = 5-chloro-7-iodo-8-hydroxylquinoline) were synthesized. Compounds 1-4 showed high anti-proliferative cytotoxicities against BEL-7404, SK-OV-3, NCI-H460 tumor cells, and HL-7702 normal cells in vitro, with IC₅₀ values in the 1.4 nM to 32.13 μM range. Compounds 2-4 exhibited significantly enhanced cytotoxicity against BEL-7404 cell line, comparing with free 5,7-dihalo-8-quinolinol. Western blotting analysis showed that 2, 3 depleted mutant p53 protein in MDA-MB-231, and compound 2 decreased the ratio of Bcl-2/Bax in NCI-H460 significantly. The binding abilities of 1-4 to DNA were stronger than that of free quinolinol ligand. Intercalation is the probable binding mode for the complexes and free quinolinol ligands with DNA.

Keywords: 5,7-Dihalo-substituted-8-quinolinoline; Crystal structure; Cu(II) complex; Cytotoxicity; DNA binding; Zn(II) complex.