Synthesis, characterization and preliminary cytotoxicity assays of poly(ethylene glycol)–malonato–Pt–DACH conjugates

Oxalate 1,2-diaminocyclohexane platinum (oxaliplatin®), a successfully employed platinum compound belonging to the family of Pt–DACH complexes, has been conjugated to different molecular weight poly(ethylene glycols) (PEG) by means of peptide spacers and a malonic acid bidentate residue. Tri- and te...

Full description

Saved in:
Bibliographic Details
Published in:European journal of medicinal chemistry 2003-07, Vol.38 (7), p.739-749
Main Authors: Furin, Alessia, Guiotto, Andrea, Baccichetti, Franca, Pasut, Gianfranco, Deuschel, Christine, Bertani, Roberta, Veronese, Francesco M
Format: Article
Language:English
Subjects:
Animals
Anticancer drug
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - pharmacology
Biological and medical sciences
Chemotherapy
Cyclohexylamines - chemical synthesis
Cyclohexylamines - pharmacology
Drug Screening Assays, Antitumor
Drug Stability
Leukemia L1210 - drug therapy
Leukemia L1210 - metabolism
Magnetic Resonance Spectroscopy
Malonates - chemistry
Medical sciences
Mice
Molecular Weight
Neoplasm Transplantation
Organoplatinum Compounds - chemical synthesis
Organoplatinum Compounds - pharmacology
Oxaliplatin
Pharmacology. Drug treatments
Platinum
Poly(ethylene glycol)
Polyethylene Glycols - chemistry
Pt–DACH
Structure-Activity Relationship
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Oxalate 1,2-diaminocyclohexane platinum (oxaliplatin®), a successfully employed platinum compound belonging to the family of Pt–DACH complexes, has been conjugated to different molecular weight poly(ethylene glycols) (PEG) by means of peptide spacers and a malonic acid bidentate residue. Tri- and tetrapeptidic substrates of lysosomal enzymes were used in order to increase the release of Pt–DACH complex inside the cell following endocytosis and enzymatic degradation of the peptide spacer. Other aminoacids (e.g. norleucine) have been also employed. 1H-NMR of some conjugates was performed as characterisation of the product, while 195Pt-NMR analysis was carried out to detect the rearrangement of the platinum complex from the Pt(O,O) to the Pt(O,N) form. The compound PEG(5000)–Nle–malonato–Pt–DACH ( 4) has been tested against L1210-implanted mice and showed and appreciable increase in cytotoxicity as compared to the reference standard Cl 2PtDACH.
ISSN:0223-5234
1768-3254
DOI:10.1016/S0223-5234(03)00114-4