Bianchi Nicoletta, Borgatti Monica, Fibach Eitan, Prus Eugenia, Zuccato Cristina, Breveglieri Giulia, Baraldi Pier Giovanni, Romagnoli Romeo, Gambari Roberto
BioPharmaNet, Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, Ferrara, Italy.
Int J Mol Med. 2009 Jan;23(1):105-11.
Derivatives of distamycin A modified at the C-terminal amidine moiety and tethered to bis-epoxyethyl moieties at the N-terminal position were tested for their ability to induce erythroid differentiation in the human erythroleukemic cell line K562. None of the compounds without bis-epoxyethyl moiety were active. A comparison of the biological activity of diepoxy compounds containing different non-basic amidine-modified moieties, showed low activity of amidoxime, carbamoyl and N-methyl carbamoyl derivatives as differentiation agents. In contrast, a cyanamidine derivative, compound 3, was able to induce erythroid differentiation of K562 cells. In addition, the cyanamidine derivative 3 was able to induce HbF accumulation following treatment of cultures of erythroid precursor cells isolated from the peripheral blood of normal subjects.
对在C端脒基部分进行修饰并在N端位置连接双环氧乙基部分的放线菌素A衍生物进行了测试，以评估它们在人红白血病细胞系K562中诱导红细胞分化的能力。没有双环氧乙基部分的化合物均无活性。对含有不同非碱性脒修饰部分的双环氧化合物的生物活性进行比较，结果表明偕胺肟、氨基甲酰基和N-甲基氨基甲酰基衍生物作为分化剂的活性较低。相比之下，氰胺基衍生物化合物3能够诱导K562细胞的红细胞分化。此外，氰胺基衍生物3在处理从正常受试者外周血分离的红系前体细胞培养物后能够诱导HbF积累。
