Synthesis and biological evaluation of new cyclic amidine analogs of chlorambucil.
Article Details
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Bielawska A, Bielawski K, Muszynska A
Synthesis and biological evaluation of new cyclic amidine analogs of chlorambucil.
Farmaco. 2004 Feb;59(2):111-7.
- PubMed ID
- 14871502 [ View in PubMed]
- Abstract
A number of novel cyclic amidine analogs of chlorambucil were synthesized and examined for cytotoxicity in breast cancer cell cultures and for inhibition of topoisomerases I and II. Evaluation of the cytotoxicity of these compounds employing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and inhibition of [(3)H]-thymidine incorporation into DNA in both MDA-MB-231 and MCF-7 breast cancer cells demonstrated that these compounds were more active than chlorambucil. The degree to which these compounds inhibited cell growth breast cancer cells was directly correlated to DNA-binding affinity. These studies indicate that cyclic amidine analogs of chlorambucil are a potent catalytic inhibitor of topoisomerase II but not topoisomerase I. The highest degree of DNA binding and cytotoxicity in both MDA-MB-231 and MCF-7 breast cancer cells was observed for the compound, which possess a 4,5-dihydro-1H-imidazol moiety.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Chlorambucil DNA Nucleotide Humans UnknownCross-linking/alkylationDetails