The interactions of polynuclear platinum complexes with human serum albumin were studied. The compounds examined were the "non-covalent" analogs of the trinuclear BBR3464 as well as the dinuclear spermidine-bridged compounds differing in only the presence or absence of a central -NH(2)-(+) (BBR3571 and analogs). Thus, closely-related compounds could be compared. Evidence for pre-association, presumably through electrostatic and hydrogen-bonding, was obtained from fluorescence and circular dichroism spectroscopy and Electrospray Ionization Mass Spectrometry (ESI-MS). In the case of those compounds containing Pt-Cl bonds, further reaction took place presumably through displacement by sulfur nucleophiles. The implications for protein pre-association and plasma stability of polynuclear platinum compounds are discussed.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2803314 | PMC |
| http://dx.doi.org/10.1039/b708433c | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Spermine and spermidine SI-PPCs: Molecular dynamics reveals enhanced biomolecular interactions.
Int J Biol Macromol
October 2024
NEQC - Núcleo de Estudos em Química Computacional, Departamento de Química, ICE, Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais 36036-900, Brazil. Electronic address:
In this paper the effects on the interaction of highly positively charged substitution-inert platinum polynuclear complexes (SI-PPCs) with negatively charged DNA and heparin are examined and compared by theoretical chemistry methods. Electrostatic and hydrogen bonding interactions contribute to the overall effects on the biomolecule. Root Mean Square (RMS) deviation, Solvent Accessible Surface, RMS fluctuation, and interaction analysis all confirm similar effects on both biomolecules, dictated predominantly by the total positive charge and total number of hydrogen bonds formed.
View Article and Find Full Text PDFA Comparison of Di- and Trinuclear Platinum Complexes Interacting with Glycosaminoglycans for Targeted Chemotherapy.
ACS Med Chem Lett
September 2023
Department of Chemistry, Virginia Commonwealth University, Richmond, Virginia 23284, United States.
Heparan sulfate proteoglycans (HSPGs) and their associated proteins aid in tumor progression through modulation of biological events such as cell invasion, angiogenesis, metastasis, and immunological responses. Metalloshielding of the anionic heparan sulfate (HS) chains by cationic polynuclear platinum complexes (PPCs) prevents the HS from interacting with HS-associated proteins and thus diminishes the critical functions of HSPG. Studies herein exploring the PPC-HS interactions demonstrated that a series of PPCs varying in charge, nuclearity, distance between Pt centers, and hydrogen-bonding ability influence HS affinity.
View Article and Find Full Text PDFFrom Basics of Coordination Chemistry to Understanding Cisplatin-analogue Pt Drugs.
Curr Pharm Des
January 2023
Department of Chemistry, Faculty of Pharmacy, Medical University-Sofia, 2 Dunav St., Sofia 1000, Bulgaria.
Background: Cisplatin, a platinum complex discovered by Rosenberg in 1969, has long been known as the first metal-based anticancer agent. Since then, various similar derivatives of cisplatin have been investigated for pharmacological activity, and the approved complexes have been applied as drugs.
Objectives: The aims of the current study are: 1) to summarize the advantages and dose-limiting effects of the approved and unapproved chemotherapy platinum cytostatics, 2) to develop new strategies for the development of platinum anticancer drugs, and 3) to clarify the important factors for the mechanism of action of platinum complexes.
Effect of PdSpermine on Mice Brain-Liver Axis Metabolism Assessed by NMR Metabolomics.
Int J Mol Sci
November 2022
Department of Chemistry, CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193 Aveiro, Portugal.
Cisplatin (cDDP)-based chemotherapy is often limited by severe deleterious effects (nephrotoxicity, hepatotoxicity and neurotoxicity). The polynuclear palladium(II) compound PdSpermine (PdSpm) has emerged as a potential alternative drug, with favorable pharmacokinetic/pharmacodynamic properties. This paper reports on a Nuclear Magnetic Resonance metabolomics study to (i) characterize the response of mice brain and liver to PdSpm, compared to cDDP, and (ii) correlate brain-liver metabolic variations.
View Article and Find Full Text PDFA novel star-shaped trinuclear platinum(II) complex based on a 1,3,5-triazine core displaying potent antiproliferative activity against TNBC by the mitochondrial injury and DNA damage mechanism.
Dalton Trans
July 2022
Key Laboratory of Optoelectronic Chemical Materials and Devices of Ministry of Education, School of Optoelectronic Materials and Technologies, Jianghan University, Wuhan 430056, P. R. China.
Polynuclear platinum(II) complexes represent a class of great prospective Pt-based antitumor drugs that may expand the antitumor spectrum and overcome the clinical problems of drug resistance and side effects of platinum-based drugs. Herein, a novel star-shaped trinuclear platinum(II) complex [Pt(L-3H)Cl] (1, L = 2,4,6-tris[(2-hydroxybenzyl)(2-pyridylmethyl)amine]-1,3,5-triazine) and its monomer [Pt(L'-H)Cl] (2, L' = (2-hydroxybenzyl)(2-pyridylmethyl)amine) were synthesized and characterized. The antiproliferative activities of complexes 1 and 2 against a panel of human cancer cell lines including MDA-MB-231 (triple-negative breast cancer, TNBC), MCF-7 (breast), HepG-2 (liver), and A549 (lung) were investigated.
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!