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

Abstract

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 ]ÁnH 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.

New Pyrrole Derivatives as Promising Biological Agents: Design, Synthesis, Characterization, In Silico, and Cytotoxicity Evaluation

“…When cultured cells achieved around 60% confluence, they were detached from flasks with a nonenzymatic solution of PBS/1 mM EDTA, washed twice in PBS and immediately used for assessing the cell viability in a colorimetric cytotoxicity assay. Non-treated cells were used as controls throughout all experiments [ 2 , 70 ].…”

Antioxidant and Cytotoxic Properties of <em>Berberis vulgaris</em> (L.) Stem Bark Dry Extract

“…All assays were performed in triplicate, using CellTiter 96® AQueous One Solution Cell Proliferation Assay (MTS) kit (Promega, USA), which contains a reagent mixture of two components: MTS [3-(4,5 dimethylthiazol 2 yl) 5 (3 carboxymethoxy phenyl) 2 (4 sulfophenyl) 2H tetrazolium] and PES (phenazine ethosulphate), a cationic dye with high chemical stability which may be combined with MTS to form a stable solution [41]. The method's principle is based on the ability of metabolically active cells to reduce MTS (a yellow tetrazolium salt) to the colored formazan, which is soluble in the culture medium and can be spectrophotometrically quantified at 492 nm wavelength nm.…”

Antioxidant and Cytotoxic Properties of Berberis vulgaris (L.) Stem Bark Dry Extract

“…All the assays were performed in triplicate using the CellTiter 96 ® AQueous One Solution Cell Proliferation Assay (MTS) kit (Promega, USA). It contains a reagent mixture of two components: MTS [3-(4,5 dimethylthiazol 2 yl) 5 (3 carboxymethoxy phenyl) 2 (4 sulfophenyl) 2H tetrazolium] and PES (phenazine ethosulphate), a cationic dye with high chemical stability, which may be combined with MTS to form a stable solution [45]. The method's principle is based on the ability of metabolically active cells to reduce MTS (a yellow tetrazolium salt) to the colored formazan, which is soluble in the culture medium and can be spectrophotometrically quantified at a 492 nm wavelength.…”