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Amidine Analogues of Melphalan: Synthesis, Cytotoxic Activity, and DNA Binding Properties
Author(s) -
Bielawska Anna,
Bielawski Krzysztof,
Anchim Tomasz
Publication year - 2007
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200700001
Subject(s) - melphalan , amidine , cytotoxicity , chemistry , topoisomerase , dna , cytotoxic t cell , deoxyribonucleoside , mtt assay , in vitro , biochemistry , stereochemistry , biology , multiple myeloma , immunology
Design, synthesis, and cytotoxic activity of amidine derivatives of melphalan are described and structure‐activity relationships are discussed. Evaluation of the cytotoxicity of these compounds employing a MTT assay and inhibition of [ 3 H]thymidine incorporation into DNA in both MDA‐MB‐231 and MCF‐7 human breast cancer cells demonstrated that these compounds were more active than melphalan. Data from the ethidium displacement assay showed that these compounds were able to bind in the minor groove‐binding mode in AT sequences of DNA. The cytotoxic properties of the amidine analogues of melphalan towards cultured human breast cancer cells correlate with topoisomerase II inhibitory properties but not with DNA‐binding properties.