Cholic Acid-carboplatin Compounds (CarboChAPt) as Models for Specific Drug Delivery: Synthesis of Novel Carboplatin Analogous Derivatives and Comparison of the Cytotoxic Properties with Corresponding Cisplatin Compounds
Abstract
This report continues our work on new compounds which consist of three functional parts—a transport fragment, a spacer and a biologically active 'drug' component. Here cholic acid functions as the transport fragment, linked via an alkyl spacer to a carboplatin analog, representing the drug (carbo-ChAPt—Fig. 1). We describe the synthesis and characterization of the series of complexes [Pt(Cyclobutane-1,1-dicarboxylato)(diamine)], {diamine=CholCOO(CH2)nCH(CH2NH2)2 and THP(CH2)nCH-(CH2NH2)2, n=4, 6, 8, 11}. The compounds were characterized by elemental analysis and NMR-measurements. Cytostatic activity data are given. In general, the cytostatic activity is similar to that of the parent compound and is strongly influenced by the length of the alkyl chain spacer separating the drug and transport fragments, the ones with long chain spacers being more toxic than the parent complexes. Preliminary investigations indicate the ability of the ChAPt to break resistance of tumor cells against common platinum tumor drugs, e.g. cisplatin. They are effective even on cell lines that have developed resistance to other drugs such as cis- and carboplatin. They are more cytotoxic so they are potentially effective at lower dose concentrations. The mode of cell death was examined by trypan-blue exclusion test and DNA gelelectrophoresis. Typical fragmentation of DNA was observed and the cells were still able to exclude trypan-blue.
Recommended Citation
R. Paschke et al., "Cholic Acid-carboplatin Compounds (CarboChAPt) as Models for Specific Drug Delivery: Synthesis of Novel Carboplatin Analogous Derivatives and Comparison of the Cytotoxic Properties with Corresponding Cisplatin Compounds," Journal of Inorganic Biochemistry, Elsevier, Apr 2003.
The definitive version is available at https://doi.org/10.1016/S0162-0134(03)00024-2
Department(s)
Chemistry
Sponsor(s)
Land Sachsen-Anhalt
Keywords and Phrases
Bile acids
International Standard Serial Number (ISSN)
0162-0134
Document Type
Article - Journal
Document Version
Citation
File Type
text
Language(s)
English
Rights
© 2003 Elsevier, All rights reserved.
Publication Date
01 Apr 2003