Wasowska-Lukawska Malgorzata, Wietrzyk Joanna, Opolski Adam, Oszczapowicz Janusz, Oszczapowicz Irena
Department of Modified Antibiotics, Institute of Biotechnology and Antibiotics, 5 Staroscinska Str., 02-516 Warsaw, Poland.
In Vivo. 2007 Mar-Apr;21(2):413-6.
In the search for new derivatives of daunorubicin with high activity and/or the ability to overcome the drug resistance barrier of cancer cells, some new analogs of amidino-daunorubicin, containing the chiral substituent in the formamidine group (-N=CH-N<) at the C-3' position of daunosamine moiety, have been synthesized. In order to estimate the influence of the configuration of the chiral group on the biological properties of the new derivatives of daunorubicin, three chiral amines, namely 1-cyclohexyl-ethylamine, 1-phenylethylamine and N-methyl-l-phenyl-ethylamine, both R and S isomers and their racemates, were used. These new compounds were tested for their cytotoxic activity in vitro against the cells of A549, SW707, T47D and HCV29T cancer lines. The resistance index (RI) values were obtained using the cells of the sensitive LoVo, MES-SA, HL-60 human cancer cell lines, as well as their resistant sublines (LoVo/Dx, MES-SAIDX5 and HL-60/MX2, respectively). All obtained derivatives appeared to be able to overcome the drug resistance barrier of cancer cells.
在寻找具有高活性和/或克服癌细胞耐药性障碍能力的柔红霉素新衍生物的过程中，已经合成了一些氨脒基柔红霉素的新类似物，这些类似物在柔红糖胺部分的C-3'位置的脒基（-N=CH-N<）中含有手性取代基。为了评估手性基团的构型对柔红霉素新衍生物生物学性质的影响，使用了三种手性胺，即1-环己基乙胺、1-苯乙胺和N-甲基-1-苯乙胺，包括R和S异构体及其外消旋体。测试了这些新化合物对A549、SW707、T47D和HCV29T癌细胞系细胞的体外细胞毒性活性。使用敏感的LoVo、MES-SA、HL-60人癌细胞系及其耐药亚系（分别为LoVo/Dx、MES-SA/DX5和HL-60/MX2）的细胞获得耐药指数（RI）值。所有得到的衍生物似乎都能够克服癌细胞的耐药性障碍。
