{"title":"An investigation into substitution-kinetics, biomolecular responses and multimodal anticancer potential of a dihalide Pd(II) complex.","authors":"Tapan Kumar Mondal, Subrata Mandal, Pulak Jana, Rahul Naskar, Arpan Halder, Biswajit Bera, Krishnananda Chattopadhyay","doi":"10.1002/asia.202401832","DOIUrl":null,"url":null,"abstract":"<p><p>This study addresses a novel palladium dihalide complex, cis-[Pd(PCAH)Cl2] (C1), as a promising anticancer agent. XRD analysis reveals a deformed square planar geometry stabilized by hydrogen bonds and π•••π interactions. The M-Cl bonds in C1 demonstrate susceptibility to nucleophilic substitution by 2,2'-bipyridine (Bpy), with kinetic parameters evaluated using spectrophotometry. Fluorometric and spectrophotometric investigations demonstrate that C1 binds to CT DNA and protein with an avidity of around 105 M-1. The interaction with DNA is multifaceted, employing covalent bonding and intercalation, as supported by viscosity measurements. Fluorescence lifetime experiments illustrate that C1 produces static dampening of BSA fluorescence, implying structural adjustments near the tryptophan residue, further corroborated by spectroscopic analyses. The pair's (BSA and C1) FRET distance has also been computed. In vitro cytotoxicity tests suggest that C1 selectively suppresses the growth of breast carcinoma, MDA-MB-231 with IC50 = 20 ± 2.64 μM, while showing minimal effects on non-cancerous HEK-293 cells. The mechanism of action includes the creation of ROS, leading to mitochondrial apoptosis, as evidenced by various assays, including annexin-V-FITC/PI labeling. Overall, compound C1 exhibits encouraging promise as a selective anticancer drug with a ROS-triggered apoptotic mechanism, particularly effective against breast carcinoma MDA-MB-231 cells.</p>","PeriodicalId":145,"journal":{"name":"Chemistry - An Asian Journal","volume":" ","pages":"e202401832"},"PeriodicalIF":3.5000,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemistry - An Asian Journal","FirstCategoryId":"1","ListUrlMain":"https://doi.org/10.1002/asia.202401832","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
This study addresses a novel palladium dihalide complex, cis-[Pd(PCAH)Cl2] (C1), as a promising anticancer agent. XRD analysis reveals a deformed square planar geometry stabilized by hydrogen bonds and π•••π interactions. The M-Cl bonds in C1 demonstrate susceptibility to nucleophilic substitution by 2,2'-bipyridine (Bpy), with kinetic parameters evaluated using spectrophotometry. Fluorometric and spectrophotometric investigations demonstrate that C1 binds to CT DNA and protein with an avidity of around 105 M-1. The interaction with DNA is multifaceted, employing covalent bonding and intercalation, as supported by viscosity measurements. Fluorescence lifetime experiments illustrate that C1 produces static dampening of BSA fluorescence, implying structural adjustments near the tryptophan residue, further corroborated by spectroscopic analyses. The pair's (BSA and C1) FRET distance has also been computed. In vitro cytotoxicity tests suggest that C1 selectively suppresses the growth of breast carcinoma, MDA-MB-231 with IC50 = 20 ± 2.64 μM, while showing minimal effects on non-cancerous HEK-293 cells. The mechanism of action includes the creation of ROS, leading to mitochondrial apoptosis, as evidenced by various assays, including annexin-V-FITC/PI labeling. Overall, compound C1 exhibits encouraging promise as a selective anticancer drug with a ROS-triggered apoptotic mechanism, particularly effective against breast carcinoma MDA-MB-231 cells.
期刊介绍:
Chemistry—An Asian Journal is an international high-impact journal for chemistry in its broadest sense. The journal covers all aspects of chemistry from biochemistry through organic and inorganic chemistry to physical chemistry, including interdisciplinary topics.
Chemistry—An Asian Journal publishes Full Papers, Communications, and Focus Reviews.
A professional editorial team headed by Dr. Theresa Kueckmann and an Editorial Board (headed by Professor Susumu Kitagawa) ensure the highest quality of the peer-review process, the contents and the production of the journal.
Chemistry—An Asian Journal is published on behalf of the Asian Chemical Editorial Society (ACES), an association of numerous Asian chemical societies, and supported by the Gesellschaft Deutscher Chemiker (GDCh, German Chemical Society), ChemPubSoc Europe, and the Federation of Asian Chemical Societies (FACS).