RuIII-Morpholine-Derived Thiosemicarbazone-Based Metallodrugs: Lysosome-Targeted Anticancer Agents.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Monalisa Mohanty, Sanchita Das, Pratikshya Das Pattanayak, Sudhir Lima, Werner Kaminsky, Rupam Dinda
{"title":"Ru<sup>III</sup>-Morpholine-Derived Thiosemicarbazone-Based Metallodrugs: Lysosome-Targeted Anticancer Agents.","authors":"Monalisa Mohanty, Sanchita Das, Pratikshya Das Pattanayak, Sudhir Lima, Werner Kaminsky, Rupam Dinda","doi":"10.1021/acsabm.4c01536","DOIUrl":null,"url":null,"abstract":"<p><p>The idea of coordinating biologically active ligand systems to metal centers to exploit their synergistic effects has gained momentum. Therefore, in this report, three Ru<sup>III</sup> complexes <b>1</b>-<b>3</b> of morpholine-derived thiosemicarbazone ligands have been prepared and characterized by spectroscopy and HRMS along with the structure of <b>2</b> through a single-crystal X-ray diffraction study. The solution stability of <b>1</b>-<b>3</b> was tested using conventional techniques such as UV-vis and HRMS. Further, the anticancer activity of <b>1</b>-<b>3</b> was tested in HT-29 and HeLa cancer cell lines. To gain insight into their mechanism of action, the cytotoxicity, hydrophobicity, and the interaction of <b>1</b>-<b>3</b> with DNA and HSA were evaluated by different conventional methods such as absorption, fluorescence, and circular dichroism studies. Along with favorable biomolecule interaction, <b>1</b>-<b>3</b> revealed potent selectivity toward cancer cells, which is a prerequisite for the generation of an anticancer drug. According to cell viability results, <b>1</b> has the highest cytotoxicity among all in the group, against both cells, respectively. Additionally, the fluorescence-active ruthenium complexes selectively target lysosomes, which is evaluated by live-cell imaging. <b>1</b>-<b>3</b> disrupt the lysosome membrane potential by generating an excessive amount of reactive oxygen species, which results in an apoptotic mode of cell death.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1021/acsabm.4c01536","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0

Abstract

The idea of coordinating biologically active ligand systems to metal centers to exploit their synergistic effects has gained momentum. Therefore, in this report, three RuIII complexes 1-3 of morpholine-derived thiosemicarbazone ligands have been prepared and characterized by spectroscopy and HRMS along with the structure of 2 through a single-crystal X-ray diffraction study. The solution stability of 1-3 was tested using conventional techniques such as UV-vis and HRMS. Further, the anticancer activity of 1-3 was tested in HT-29 and HeLa cancer cell lines. To gain insight into their mechanism of action, the cytotoxicity, hydrophobicity, and the interaction of 1-3 with DNA and HSA were evaluated by different conventional methods such as absorption, fluorescence, and circular dichroism studies. Along with favorable biomolecule interaction, 1-3 revealed potent selectivity toward cancer cells, which is a prerequisite for the generation of an anticancer drug. According to cell viability results, 1 has the highest cytotoxicity among all in the group, against both cells, respectively. Additionally, the fluorescence-active ruthenium complexes selectively target lysosomes, which is evaluated by live-cell imaging. 1-3 disrupt the lysosome membrane potential by generating an excessive amount of reactive oxygen species, which results in an apoptotic mode of cell death.

求助全文
约1分钟内获得全文 求助全文
来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
期刊介绍: ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信