João A. V. Santos, Maria M. Félix, Clara B. Martins, Joana Marques, M. Paula M. Marques, Luís A. E. Batista de Carvalho
{"title":"钯(II)抗癌剂:pd -精胺复合物的复杂情况","authors":"João A. V. Santos, Maria M. Félix, Clara B. Martins, Joana Marques, M. Paula M. Marques, Luís A. E. Batista de Carvalho","doi":"10.1039/d5dt01835h","DOIUrl":null,"url":null,"abstract":"Palladium-based anticancer drugs are promising alternatives to platinum agents, with potential to overcome acquired resistance and reduce side effects. Among them, the dinuclear Pd(<small>II</small>)–spermine complex (Pd<small><sub>2</sub></small>Spm) has shown notable cytostatic activity <em>in vitro</em>. However, its synthesis mechanism and structural properties remain poorly understood, which hinders further development. This study reports an optimised synthetic route for Pd<small><sub>2</sub></small>Spm, revealing pH dependence and temperature-induced isomeric changes. These variations were thoroughly characterised by vibrational spectroscopy, leading to the identification of the pure diastereomer (<em>R</em>,<em>S</em>), the enantiomeric mixture ((<em>R</em>,<em>R</em>) and (<em>S</em>,<em>S</em>)) and the mixture containing these three isomers. Cell viability tests were carried out in the human triple negative breast cancer MDA-MB-231 cell line for the diastereomer and the enantiomers and diastereomer mixture, demonstrating equivalent results for these entities (IC<small><sub>50</sub></small> equal to 2.7 and 2.6 μM at 72 h, respectively). This is the first report of an optimised synthesis and anticancer <em>in vitro</em> assays for a well-defined Pd<small><sub>2</sub></small>Spm structure. The present findings strengthen the potential of Pd<small><sub>2</sub></small>Spm as a next-generation anticancer metallodrug, paving the way for preclinical trials.","PeriodicalId":71,"journal":{"name":"Dalton Transactions","volume":"35 1","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Palladium(II) anticancer agents: the intricate case of the Pd–spermine complex\",\"authors\":\"João A. V. Santos, Maria M. Félix, Clara B. Martins, Joana Marques, M. Paula M. Marques, Luís A. E. Batista de Carvalho\",\"doi\":\"10.1039/d5dt01835h\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Palladium-based anticancer drugs are promising alternatives to platinum agents, with potential to overcome acquired resistance and reduce side effects. Among them, the dinuclear Pd(<small>II</small>)–spermine complex (Pd<small><sub>2</sub></small>Spm) has shown notable cytostatic activity <em>in vitro</em>. However, its synthesis mechanism and structural properties remain poorly understood, which hinders further development. This study reports an optimised synthetic route for Pd<small><sub>2</sub></small>Spm, revealing pH dependence and temperature-induced isomeric changes. These variations were thoroughly characterised by vibrational spectroscopy, leading to the identification of the pure diastereomer (<em>R</em>,<em>S</em>), the enantiomeric mixture ((<em>R</em>,<em>R</em>) and (<em>S</em>,<em>S</em>)) and the mixture containing these three isomers. Cell viability tests were carried out in the human triple negative breast cancer MDA-MB-231 cell line for the diastereomer and the enantiomers and diastereomer mixture, demonstrating equivalent results for these entities (IC<small><sub>50</sub></small> equal to 2.7 and 2.6 μM at 72 h, respectively). This is the first report of an optimised synthesis and anticancer <em>in vitro</em> assays for a well-defined Pd<small><sub>2</sub></small>Spm structure. The present findings strengthen the potential of Pd<small><sub>2</sub></small>Spm as a next-generation anticancer metallodrug, paving the way for preclinical trials.\",\"PeriodicalId\":71,\"journal\":{\"name\":\"Dalton Transactions\",\"volume\":\"35 1\",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-10-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Dalton Transactions\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1039/d5dt01835h\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, INORGANIC & NUCLEAR\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Dalton Transactions","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1039/d5dt01835h","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, INORGANIC & NUCLEAR","Score":null,"Total":0}
Palladium(II) anticancer agents: the intricate case of the Pd–spermine complex
Palladium-based anticancer drugs are promising alternatives to platinum agents, with potential to overcome acquired resistance and reduce side effects. Among them, the dinuclear Pd(II)–spermine complex (Pd2Spm) has shown notable cytostatic activity in vitro. However, its synthesis mechanism and structural properties remain poorly understood, which hinders further development. This study reports an optimised synthetic route for Pd2Spm, revealing pH dependence and temperature-induced isomeric changes. These variations were thoroughly characterised by vibrational spectroscopy, leading to the identification of the pure diastereomer (R,S), the enantiomeric mixture ((R,R) and (S,S)) and the mixture containing these three isomers. Cell viability tests were carried out in the human triple negative breast cancer MDA-MB-231 cell line for the diastereomer and the enantiomers and diastereomer mixture, demonstrating equivalent results for these entities (IC50 equal to 2.7 and 2.6 μM at 72 h, respectively). This is the first report of an optimised synthesis and anticancer in vitro assays for a well-defined Pd2Spm structure. The present findings strengthen the potential of Pd2Spm as a next-generation anticancer metallodrug, paving the way for preclinical trials.
期刊介绍:
Dalton Transactions is a journal for all areas of inorganic chemistry, which encompasses the organometallic, bioinorganic and materials chemistry of the elements, with applications including synthesis, catalysis, energy conversion/storage, electrical devices and medicine. Dalton Transactions welcomes high-quality, original submissions in all of these areas and more, where the advancement of knowledge in inorganic chemistry is significant.