3-Chlorpiperidine als DNA-Alkylantien
Synthesis and structure-activity relationships of bis-3-chloropiperidines
as bifunctional DNA alkylating agents
Bifunctional alkylating agents such as chlorambucil and melphalan represent an important class of clinical cancer chemotherapeutics. The antitumor antibiotics azinomycin A and B have the ability to alkylate and crosslink DNA. However, their poor chemical stability suggests that these natural products are unlikely to progress as therapeutic candidates. Yet they can act as lead structures from which to develop potentially useful new molecules. Due to our interest in developing more effective bifunctional alkylating agents, we designed novel bis-3-chloropiperidines based upon the azinomycins backbone.
The nitrogen mustard moiety is more stable than the natural products and the alkylating functions generated via intermediate aziridinium ions are positioned in a similar distance as has been observed for the azinomycins.
Accordingly, we synthesised a series of derivatives and evaluated the alkylating properties by performing a DNA cleavage assay. Furthermore, in vitro cell cytotoxicity studies of these compounds are currently being carried out.
| Projekt director: | Prof. Dr. Richard Göttlich |
| Co-workers: | M. Sc. Mats Georg |
| M. Sc. Michael Kirchner | |
| M. Sc. Jana Semmler |