Recently it has been shown that several analogues of the clinically ineffective trans-DDP exhibit antitumor activity comparable to that of cis-DDP. The present paper describes the binding of antitumor trans-[PtCl(2)(E-iminoether)(2)] (trans-EE) to guanosinemonophosphate (GMP) and adenosinemonophosphate (AMP). We have used HPLC and (1)H and (15)N NMR to characterize the different adducts. In the case of a 1:1 mixture of trans-EE and GMP, at an early stage of the reaction, a monofunctional adduct is formed which, subsequently, is partly converted into a monosolvated monofunctional species. After about 70 hours an equilibrium is established between chloro and solvato monofunctional adducts at a ratio of 30/70. In the presence of excess GMP (4:1) the initially formed monofunctional adducts react further to give two bifunctional adducts, one with the iminoether ligands in their original E configurations and the other with the iminoether ligands having one E and the other, Z configurations. The coordination geometry obtained by energy minimization calculations is in qualitative agreement with 2D NMR data.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2365223 | PMC |
| http://dx.doi.org/10.1155/MBD.2000.169 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Adenine-adenine, adenine-cytosine and cytosine-cytosine intrastrand crosslinks induced by a photoactivatable Pt(IV) anticancer prodrug.
Dalton Trans
December 2023
Key Laboratory of Hubei Province for Coal Conversion and New Carbon Materials; School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, P. R. China.
Four trinucleotides 5'-ATA-3' (I), 5'-ATC-3' (II), 5'-CTA-3' (III) and 5'-CTC-3' (IV) were introduced to interact with a diazido-based photoactivatable anticancer prodrug ,,-[Pt(N)(OH)(py)] (py = pyridine; 1) upon light irradiation. Using electrospray ionization mass spectrometry (ESI-MS), we aimed to investigate the possibility of 1,3-intrastrand crosslinks at adenine and/or cytosine in the trinucleotides the bi-functional -[Pt(py)] species generated by photodecomposition of complex 1. The primary mass spectrometry results showed that although mono- and di-platinated trinucleotides bound by mono-functional -[Pt(N)(py)] species were the major platinated adducts, comparable amounts of bifunctional -[Pt(py)]-bound trinucleotides were also observed.
View Article and Find Full Text PDFAlkylation of nucleobases by 2-chloro--diethylethanamine hydrochloride (CDEAH) sensitizes -deficient tumors.
NAR Cancer
September 2023
Center for Genomic Integrity, Institute for Basic Science, Ulsan 44919, Republic of Korea.
Targeting - and -deficient tumors through synthetic lethality using poly(ADP-ribose) polymerase inhibitors (PARPi) has emerged as a successful strategy for cancer therapy. PARPi monotherapy has shown excellent efficacy and safety profiles in clinical practice but is limited by the need for tumor genome mutations in or other homologous recombination genes as well as the rapid emergence of resistance. In this study, we identified 2-chloro--diethylethanamine hydrochloride (CDEAH) as a small molecule that selectively kills - and xeroderma pigmentosum A-deficient cells.
View Article and Find Full Text PDFTime-temperature superposition for kinetic mapping of solventless autocatalytic addition of diisocyanates and macrodiols.
RSC Adv
March 2023
University of Clermont Auvergne/CNRS (French National Centre for Scientific Research), Currently with Recycle Consultants Clermont-Ferrand France.
The migration of chemicals from polyurethane (PUR) is a concern in many applications, such as adhesives for food packaging. Low molecular weight catalysts, which are prone to migration, need to be eliminated from PUR, in particular those containing Sn or other metals. This is difficult partly due to many uncertainties of autocatalytic polyaddition between isocyanates and polyols.
View Article and Find Full Text PDFSpontaneous Water Radical Cation Oxidation at Double Bonds in Microdroplets.
Front Chem
April 2022
Department of Chemistry and Center for Analytical Instrumentation Development, Purdue University, West Lafayette, IN, United States.
Spontaneous oxidation of compounds containing diverse X=Y moieties (e.g., sulfonamides, ketones, esters, sulfones) occurs readily in organic-solvent microdroplets.
View Article and Find Full Text PDFProcessing and Bypass of a Site-Specific DNA Adduct of the Cytotoxic Platinum-Acridinylthiourea Conjugate by Polymerases Involved in DNA Repair: Biochemical and Thermodynamic Aspects.
Int J Mol Sci
October 2021
Czech Academy of Sciences, Institute of Biophysics, Kralovopolska 135, CZ 61265 Brno, Czech Republic.
DNA-dependent DNA and RNA polymerases are important modulators of biological functions such as replication, transcription, recombination, or repair. In this work performed in cell-free media, we studied the ability of selected DNA polymerases to overcome a monofunctional adduct of the cytotoxic/antitumor platinum-acridinylthiourea conjugate [PtCl(en)(L)](NO) (en = ethane-1,2-diamine, L = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea) (ACR) in its favored 5'-CG sequence. We focused on how a single site-specific ACR adduct with intercalation potency affects the processivity and fidelity of DNA-dependent DNA polymerases involved in translesion synthesis (TLS) and repair.
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!