PubMed:14871502 JSONTXT

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":190,"end":203},"obj":"HP_0003002"},{"id":"T2","span":{"begin":190,"end":203},"obj":"HP_0100013"},{"id":"T3","span":{"begin":197,"end":203},"obj":"HP_0002664"},{"id":"T4","span":{"begin":481,"end":494},"obj":"HP_0003002"},{"id":"T5","span":{"begin":481,"end":494},"obj":"HP_0100013"},{"id":"T6","span":{"begin":488,"end":494},"obj":"HP_0002664"},{"id":"T7","span":{"begin":629,"end":642},"obj":"HP_0003002"},{"id":"T8","span":{"begin":629,"end":642},"obj":"HP_0100013"},{"id":"T9","span":{"begin":636,"end":642},"obj":"HP_0002664"},{"id":"T10","span":{"begin":923,"end":936},"obj":"HP_0003002"},{"id":"T11","span":{"begin":923,"end":936},"obj":"HP_0100013"},{"id":"T12","span":{"begin":930,"end":936},"obj":"HP_0002664"}],"text":"Synthesis and biological evaluation of new cyclic amidine analogs of chlorambucil.\nA 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."}