AUTHOR=Banti C. N. , Tasiopoulos A. J. , Hadjikakou S. K. 

TITLE=Conjugation of an anti-metabolite nucleobase analogue with a mitochondriotropic agent via palladium(II) against breast cancer cells

JOURNAL=Frontiers in Chemical Biology

VOLUME=3

YEAR=2024

URL=https://www.frontiersin.org/journals/chemical-biology/articles/10.3389/fchbi.2024.1338630

DOI=10.3389/fchbi.2024.1338630

ISSN=2813-530X

ABSTRACT=<p>The conjugation of the uracil (a nucleobase) analogue, 6-methyl-thiouracil (MTUC), with the mitochondriotropic agent of Tri-o-Tolyl-Phosphine (TOTP) through palladium(II) leads to the formation of the metallodrug of formula [PdCl(TOTP)(MTUC)] (<bold>1</bold>). The metallodrug was characterized in solid state using Attenuated Total Reflectance-Fourier Transform Infra-Red (ATR-FTIR) spectroscopy and X-ray diffraction crystallography (XRD), while its behavior in solution was examined through Ultra Violet (UV) and <sup>1</sup>H NMR spectroscopies. The <italic>in vitro</italic> cytotoxicity of <bold>1</bold> was assessed against human breast adenocarcinoma cell lines: MCF-7 (hormone-dependent (HD)) and MDA-MB-231 (hormone-independent (HI)), as well as fetal lung fibroblast (MRC-5) cells. The MCF-7 cell morphology suggests apoptotic pathway, and this was confirmed by Acridine Orange/Ethidium Bromide (AO/EB) Staining, and the loss of the permeabilization of the mitochondrial membrane. The binding affinity of 1 toward the calf thymus (CT) DNA was clarified.</p>