Synthesis, characterization, DNA/BSA interactions and in vitro cytotoxicity study of palladium(II) complexes of hispolon derivatives.

Thirteen novel palladium(II) complexes of the general formula [Pd(bipy)(O , O ′-dkt)](PF 6), (where bipy is 2,2′-bipyridine and O , O ′-dkt is β-diketonate ligand hispolon or its derivative) have been prepared through a metal-ligand coordination method that involves spontaneous formation of the corresponding diketonate scaffold. The obtained palladium(II) complexes have been characterized by NMR spectroscopy, ESI-mass spectrometry as well as elemental analysis. The cytotoxicity analysis indicates that most of the obtained palladium(II) complexes show promising growth inhibition in three human cancer cell lines. Flow cytometry analysis shows complex 3e could promote intracellular reactive oxygen species (ROS) accumulation and lead cancer cell death. And the suppression of ROS accumulation and the rescue of cell viability in HeLa cells by N -acetyl-L-cysteine (NAC) suggest the possible link between the increase in ROS generation and cytotoxicity of complex 3e. Flow cytometry analysis also reveal that complex 3e cause cell cycle arrest in the G2/M phase and collapse of the mitochondrial membrane potential, promote the generation of ROS and lead to tumor cell apoptosis. The interactions of complex 3e with calf thymus DNA (CT-DNA) have been evaluated by UV–Vis spectroscopy, fluorescence quenching experiments and viscosity measurements, which reveal that the complex interact with CT-DNA through minor groove binding and/or electrostatic interactions. Further, the results of fluorescence titration and site marker competitive experiment on bovine serum albumin (BSA) suggest that complex 3e can quench the fluorescence of BSA via a static quenching process and bind to BSA in Sudlow's site II. Thirteen palladium (II) complexes of hispolon derivatives were synthesized. Most of them possess promising growth inhibition activities. Mechanistic studies indicate that complex 3e cause cell cycle arrest in the G2/M phase, reactive oxygen species (ROS) accumulation and cell apoptosis. Its interactions with DNA/BSA (bovine serum albumin) have also been studied. Unlabelled Image • A novel series of palladium (II) complexes of hispolon derivatives was obtained. • Most complexes were found to be more toxic against HeLa than MCF-7 and MGC803 cells. • Complex 3e inhibits HeLa cells proliferation via apoptosis induction and cell cycle arrest. • Minor groove binding and/or electrostatic interactions of complex 3e with DNA were found. • Complex 3e exhibits moderate binding affinity toward BSA (bovine serum albumin). [ABSTRACT FROM AUTHOR]