{"title":"Conjugation of an anti-metabolite nucleobase analogue with a mitochondriotropic agent via palladium(II) against breast cancer cells","authors":"C. Banti, A. J. Tasiopoulos, S. Hadjikakou","doi":"10.3389/fchbi.2024.1338630","DOIUrl":null,"url":null,"abstract":"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)] (1). 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 1H NMR spectroscopies. The in vitro cytotoxicity of 1 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.","PeriodicalId":123291,"journal":{"name":"Frontiers in Chemical Biology","volume":"27 11","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Chemical Biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3389/fchbi.2024.1338630","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
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)] (1). 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 1H NMR spectroscopies. The in vitro cytotoxicity of 1 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.