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.

Bis-epoxyethyl derivatives of distamycin A modified on the amidino moiety: Induction of production of fetal hemoglobin in human erythroid precursor cells

BIANCHI, Nicoletta
Primo
;
BORGATTI, Monica
Secondo
;
ZUCCATO, Cristina;BREVEGLIERI, Giulia;BARALDI, Pier Giovanni;ROMAGNOLI, Romeo
Penultimo
;
GAMBARI, Roberto
Ultimo
2009

Abstract

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.
2009
Bianchi, Nicoletta; Borgatti, Monica; Fibach, E; Prus, E; Zuccato, Cristina; Breveglieri, Giulia; Baraldi, Pier Giovanni; Romagnoli, Romeo; Gambari, R...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/533486
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