研究动态
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活性:C-7取代的环状缩醛衍生物对低氧和氧化的EMT6癌细胞体内外的丝裂霉素C和波尔福霉素的影响。

Activity of C-7 substituted cyclic acetal derivatives of mitomycin C and porfiromycin against hypoxic and oxygenated EMT6 carcinoma cells in vitro and in vivo.

发表日期:1991 Jun
作者: S Rockwell, S R Keyes, R Loomis, M Kelley, D M Vyas, H Wong, T W Doyle, A C Sartorelli
来源: Cancer Communications

摘要:

一系列环戊二醚衍生物对低氧和富氧 EMT6 肿瘤细胞的杀伤能力进行了测试,包括米托霉素-C(MC)和卟吩霉素(POR)。在 MC 和 POR 的 C-7 处进行氨甲基环戊二醚和硫醚环戊二醚取代,可明显提高化合物对低氧 EMT6 肿瘤细胞的细胞毒性,但对富氧毒性的影响不大。相反地,N1a 处的甲基取代显著降低了化合物的富氧细胞毒性,但未改变低氧细胞毒性。POR 环戊二醚 BMY-42355 在 MC 类似物中观察到低氧和富氧细胞毒性之间的最大差异。小鼠的初步研究表明,BMY-42355 单独或与放射线联用对抗癌活性良好,毒性低于 POR;该化合物在这些初步研究中的治疗比为 MC 或 POR 的任何一个都更高。
A series of cyclic acetal derivatives of mitomycin C (MC) and porfiromycin (POR) were tested for their ability to kill hypoxic and oxygenated EMT6 tumor cells. Amino methyl acetal and thioacetal substitutions at C-7 of MC and POR dramatically increased the cytotoxicity of the compounds to hypoxic EMT6 tumor cells in vitro but had little effect on the aerobic toxicities. In contrast, a methyl substitution at N1a markedly decreased the aerobic cytotoxicities of the compounds but did not alter the hypoxic cytotoxicities. The POR acetal, BMY-42355, had the largest differential between hypoxic and aerobic cytotoxicities yet observed among MC analogs. Preliminary studies in mice showed that BMY-42355 had good antineoplastic activity when used alone or in combination with radiation and was less toxic than POR; the therapeutic ratio of this compound in these initial studies was higher than those of either MC or POR.