Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Synthesis and biological activity of water-soluble maleimide derivatives of the anticancer drug Carboplatin designed as albumin-binding prodrugs

Item Type:Article
Title:Synthesis and biological activity of water-soluble maleimide derivatives of the anticancer drug Carboplatin designed as albumin-binding prodrugs
Creators Name:Warnecke, A. and Fichtner, I. and Garmann, D. and Jaehde, U. and Kratz, F.
Abstract:Four platinum (II) complexes (13-16) were synthesized by reacting either [Pt trans-DACH](NO3)2 with a 6-maleimidocaproic acid, a 15-maleimido-4,7,10,13-tetroxapentadecanoic acid, and a 6-maleimido-4-oxacaproic ester derivative of cyclobutane-1,1-dicarboxylic acid (CDBA) or [Pt(NH 3)2](NO3)2 with a 6-maleimido-4-oxacaproic ester derivative of CBDA. Both complexes containing the 6-maleimido-4-oxacaproic ester (15, 16) showed good water solubility (≥8 mg/mL) and CE experiments revealed rapid binding to human serum albumin and the formation of biadducts with dGMP and dAMP. In the MaTu xenograft model in nude mice, both complexes showed an improved antitumor effect at their maximum tolerated dose (2 × 50 mg/kg carboplatin equivalents) compared to therapy with carboplatin at equimolar dose or at its optimal dose (2 × 75 mg/kg).
Keywords:Antineoplastic Agents, Carboplatin, Maleimides, Neoplasm Transplantation, Nude Mice, Prodrugs, Protein Binding, Serum Albumin, Solubility, Tumor Cell Line, Water, Xenograft Model Antitumor Assays, Animals, Mice
Source:Bioconjugate Chemistry
ISSN:1043-1802
Publisher:Amer Chemical Soc (U.S.A.)
Volume:15
Number:6
Page Range:1349-1359
Date:1 November 2004
Official Publication:https://doi.org/10.1021/bc049829j
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library