Bielawska Anna, Bielawski Krzysztof, Anchim Tomasz
Department of Medicinal Chemistry and Drug Technology, Medical University of Bialystok, Bialystok, Poland.
Arch Pharm (Weinheim). 2007 May;340(5):251-7. doi: 10.1002/ardp.200700001.
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.
描述了美法仑脒衍生物的设计、合成及细胞毒性活性，并讨论了构效关系。采用MTT法评估这些化合物的细胞毒性，以及在MDA-MB-231和MCF-7人乳腺癌细胞中对[³H]胸腺嘧啶掺入DNA的抑制作用，结果表明这些化合物比美法仑更具活性。溴化乙锭置换试验的数据表明，这些化合物能够以小沟结合模式结合于DNA的AT序列中。美法仑脒类似物对培养的人乳腺癌细胞的细胞毒性特性与拓扑异构酶II抑制特性相关，而与DNA结合特性无关。
