New heteroleptic lanthanide complexes as multimodal drugs: Cytotoxicity studies, apoptosis, cell cycle analysis, DNA interactions, and protein binding

We report herein the synthesis and characterization of four new heteroleptic complexes of Sm(III), Eu(III), Gd(III), and Tb(III) with the natural flavonoid 5-hydroxyflavone (primuletin) and 1,10-phenanthroline. According to the physicochemical characterization, the mononuclear complexes correspond to the general formula[Ln(OH)(2)L1L2]center dot nH(2)O, where L-1= C15H9O3(deprotonated 5-hydroxyflavone) and L-2= C12H8N2(1,10-phenanthroline), Ln is the lanthanide cation, andn= 4 for Sm(III), 3.5 for Eu(III), 2 for Gd(III), and 3 for Tb(III). A six-coordinated distorted octahedron geometry was proposed for the complexes, and density functional theory (DFT) studies were used to calculate their optimized geometry. Cytotoxicity was studied using MTS assay on cervical, colorectal, colon, breast, and ovarian adenocarcinoma cell lines. Flow cytometry data were consistent with apoptotic cell death and disruption of the cell cycle in cervical and colon cancer cells. As a means to investigate the mechanism underlying the cytotoxic effects, the abilities of the complexes to interact with calf thymus DNA, human serum albumin, and transferrin have also been assessed. According to experimental and computational studies, the four lanthanide complexes act as DNA intercalators and bind strongly to serum proteins.

Automated summary

The synthesis and characterization of four new heteroleptic complexes of lanthanide metals with natural flavonoid and 1,10-phenanthroline were reported. These complexes exhibited cytotoxicity and were found to interact with DNA and serum proteins.