Shervington Leroy A, Smith Nigel, Norman Emma, Ward Timothy, Phillips Roger, Shervington Amal
School of Pharmacy and Pharmaceutical Sciences, University of Central Lancashire, Preston, UK.
Eur J Med Chem. 2009 Jul;44(7):2944-51. doi: 10.1016/j.ejmech.2008.11.014. Epub 2008 Dec 9.
Four ester prodrugs derived from the bifunctional alkylating agent chlorambucil, and one of its nitro-derivatives, 3-nitrochlorambucil conjugated to prasterone and pregnenolone, were synthesized and tested for their cytotoxic activity against eight human cell lines, using the standard MTT assay. A comparison between the esters and the controls, namely chlorambucil and 3-nitrochlorambucil would suggest that all four esters possess to varying degrees, specificity towards the breast adenocarcinoma cell line (MDA-mb468) than the other seven cells' lines tested. The overall findings are encouraging since it infers that these lipophilic esters not only have the ability to traverse specific cell membranes but also exhibit cytotoxicity towards most of the cell lines tested.
合成了四种源自双功能烷基化剂苯丁酸氮芥的酯前药,以及其一种硝基衍生物,即与普拉睾酮和孕烯醇酮共轭的3-硝基苯丁酸氮芥,并使用标准MTT法测试了它们对八种人类细胞系的细胞毒性活性。酯与对照物(即苯丁酸氮芥和3-硝基苯丁酸氮芥)之间的比较表明,所有四种酯对乳腺癌细胞系(MDA-mb468)都具有不同程度的特异性,比对其他七种测试细胞系的特异性更高。总体研究结果令人鼓舞,因为这表明这些亲脂性酯不仅有能力穿过特定的细胞膜,而且对大多数测试细胞系都表现出细胞毒性。