Cisplatin (-diamminedichloroplatinum(II)) is a potent chemotherapeutic agent commonly used to treat cancer. However, its use also leads to serious side effects, such as nephrotoxicity, ototoxicity, and cardiotoxicity, which limit the dose that can be safely administered to patients. To minimize these problems, dendrimers may be used as carriers for cisplatin through the coordination of their terminal functional groups to platinum. Here, cisplatin was conjugated to half-generation anionic PAMAM dendrimers in mono- and bidentate forms, and their biological effects were assessed in vitro. After preparation and characterization of the metallodendrimers, their cytotoxicity was evaluated against several cancer cell lines (A2780, A2780cisR, MCF-7, and CACO-2 cells) and a non-cancer cell line (BJ cells). The results showed that all the metallodendrimers were cytotoxic and that the cytotoxicity level depended on the cell line and the type of coordination mode (mono- or bidentate). Although, in this study, a correlation between dendrimer generation (number of carried metallic fragments) and cytotoxicity could not be completely established, the monodentate coordination form of cisplatin resulted in lower IC values, thus revealing a more accessible cisplatin release from the dendritic scaffold. Moreover, most of the metallodendrimers were more potent than the cisplatin, especially for the A2780 and A2780cisR cell lines, which showed higher selectivity than for non-cancer cells (BJ cells). The monodentate G0.5COO(Pt(NH)Cl) and G2.5COO(Pt(NH)Cl) metallodendrimers, as well as the bidentate G2.5COO(Pt(NH)) metallodendrimer, were even more active towards the cisplatin-resistant cell line (A2780cisR cells) than the correspondent cisplatin-sensitive one (A2780 cells). Finally, the effect of the metallodendrimers on the hemolysis of human erythrocytes was neglectable, and metallodendrimers' interaction with calf thymus DNA seemed to be stronger than that of free cisplatin.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960565 | PMC |
| http://dx.doi.org/10.3390/pharmaceutics15020689 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Effect of the Appended Morpholinyl Group on Photophysical Behavior of Mono- and Bis-cyclometalated Terpyridine Iridium(III) Chromophores.
Inorg Chem
January 2025
Institute of Chemistry, University of Silesia, Szkolna 9, 40-006 Katowice, Poland.
This paper provides extensive studies of [IrCl(Ph-py)(morph-CH-terpy-κN)]PF (), [Ir(Ph-py)(morph-CH-terpy-κN)]PF (), [IrCl(Ph-py)(Ph-terpy-κN)]PF (), and [Ir(Ph-py)(Ph-terpy-κN)]PF () designed to demonstrate the possibility of controlling the photophysical properties of mono- and bis-cyclometalated complexes [IrCl(Ph-py)(R-CH-terpy-κN)]PF and [Ir(Ph-py)(R-CH-terpy-κN)]PF through a remote electron-donating substituent introduced into the 4'-position of 2,2':6',2″-terpyridine (terpy) via the phenyl linker. The attachment of the morpholinyl (morph) group was evidenced to induce dramatic changes in the emission characteristics of the monocyclometalated Ir(III) systems with coordinated R-CH-terpy ligand (κN). In solution, the obtained complex [IrCl(Ph-py)(morph-CH-terpy-κN)]PF was found to be a rare example of dual-emissive Ir(III) systems.
View Article and Find Full Text PDFCentrality of phosphate binding modes on metal vanadate in exploiting low-temperature NO reduction and pyrosulfate dissociation pathways.
J Hazard Mater
November 2024
Department of Chemical Engineering (Integrated Engineering Program), Kyung Hee University, Yongin 17104, South Korea; KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, South Korea. Electronic address:
PO guests anchored on metal vanadate hosts are as vital as SO/SO analogues in wide exploitation for expediting acidic/redox SCR cycles or ABS pyrolysis at low temperatures. This is due to their multiple roles as a provider of Brönsted acidic bonds (BA-H) and as a dictator of the traits for labile/mobile oxygens (O/O) and oxygen vacancies (O). However, the relationships of BA (P-O)/BA-H (P-O-H)/O/O/O feature for the host versus its mono-/bi-dentate PO binding mode ( [Formula: see text] / [Formula: see text] ) has never been examined to-date.
View Article and Find Full Text PDFCobalt(II) and Manganese(II) Complexes of Sodium Monensinate A Bearing Nitrate Co-Ligands.
Int J Mol Sci
November 2024
Faculty of Chemistry and Pharmacy, Sofia University "St. Kliment Ohridski", 1164 Sofia, Bulgaria.
Monensic acid is a natural polyether ionophore and is a therapeutic of first choice in veterinary medicine for the control of coccidiosis. Although known as a sodium-binding ligand, it can also form a variety of coordination species depending on experimental conditions applied. In this study, we present the crystal structures and properties of Co(II) and Mn(II) complexes of sodium monensinate (MonNa) derived from the reaction of MonNa with cobalt or manganese dinitrates.
View Article and Find Full Text PDFHydroxamic Acids Derivatives: Greener Synthesis, Antiureolytic Properties And Potential Medicinal Chemistry Applications - A Concise Review.
Curr Top Med Chem
October 2024
Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Hydroxamic acids (HAs) are chemical compounds characterized by the general structure RCONR'OH, where R and R' can denote hydrogen, aryl, or alkyl groups. Recognized for their exceptional chelating capabilities, HAs can form mono or bidentate complexes through oxygen and nitrogen atoms, rendering them remarkably versatile. These distinctive structural attributes have paved the way for a broad spectrum of medicinal applications for HAs, among which their pivotal role as inhibitors of essential Ni(II) and Zn(II)-containing metalloenzymes.
View Article and Find Full Text PDFHelical dinuclear 3d metal complexes with bis(bidentate) [S,N] ligands: synthesis, structural and computational studies.
Dalton Trans
November 2024
School of Chemistry, University of Leicester, University Road, Leicester, LE1 7RH, UK.
A diprotic bis(β-thioketoimine) ligand precursor featuring a flexible 4,4'-methylbis(aniline) linker, H2, was synthesised treatment of the corresponding bis(β-ketoimine) with Lawesson's reagent. Lithiation of H2 and coordination with one equivalent of d-block metal(II) chlorides MCl(THF) (M = Fe, Co and Zn) yielded a corresponding series of homoleptic dinuclear complexes, [M(μ-2)]. X-ray diffraction analysis reveals a tetrahedral geometry for the two metals and a double-stranded helicate structure arising from inter-strand face-face π-stacking.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!