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New heteroleptic lanthanide complexes as multimodal drugs: Cytotoxicity studies, apoptosis, cell cycle analysis, DNA interactions, and protein binding
Author(s) -
Munteanu AlexandraCristina,
Musat Mihaela Georgiana,
Mihaila Mirela,
Badea Mihaela,
Olar Rodica,
Nitulescu George Mihai,
Rădulescu Flavian Ștefan,
Brasoveanu Lorelei Irina,
Uivarosi Valentina
Publication year - 2021
Publication title -
applied organometallic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.53
H-Index - 71
eISSN - 1099-0739
pISSN - 0268-2605
DOI - 10.1002/aoc.6062
Subject(s) - chemistry , cytotoxicity , hela , lanthanide , apoptosis , stereochemistry , cell cycle , cell , biochemistry , ion , organic chemistry , in vitro
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 L 1 L 2 ]· n H 2 O , where L 1 = C 15 H 9 O 3 (deprotonated 5‐hydroxyflavone) and L 2 = C 12 H 8 N 2 (1,10‐phenanthroline), Ln is the lanthanide cation, and n = 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.