Crystal Structures, Cytotoxicity, Cell Apoptosis Mechanism, and DNA Binding of Two 8-Hydroxylquinoline Zinc(II) Complexes

Аннотация

Two zinc(II) complexes, [Zn₄(HOQ)₆Ac₂] (I) (HOQ = 8-hydroxylquinoline) and [Zn₄(MeQ)₆Ac₂] (II) (MeQ = 2-methyl-8-hydroxylquinoline), were synthesized and characterized by IR spectroscopy, ESI-MS spectrometry, elemental analysis and single crystal X-ray diffraction analysis (CIF files CCDC nos. 1433544 (I) and 1433546 (II)). The in vitro cytotoxicity of the two complexes, which was first reported, was evaluated by MTT assay against a series of tumor cell lines as well as HL-7702 normal liver cell line. The results indicated that they showed significantly higher cytotoxicity than cispltain on BEL-7404 cells with IC₅₀ values of 11.85 ± 0.06 μM (I) and 8.40 ± 0.07 μM (II), respectively. Further apoptosis mechanism studies on BEL-7404 cells suggested that their antitumor activities were achieved through cell apoptosis and arrest at G1 or S phase. The decline of mitochondrial membrane potential, the elevation of reactive oxygen species and cytoplasmic calcium concentration ([Ca²⁺]_c), the raise of caspase-3/9 activity indicated that complexes I and II induced apoptosis of BEL-7404 by a mitochondrial dysfunction pathway. Investigations on the binding properties of complexes I and II to ct-DNA by UV-Vis, circular dichroism spectra and agarose gel electrophoresis indicated that the two complexes could bind with ct-DNA via an intercalative mode.