title: Bis-epoxyethyl derivatives of distamycin A modified on the amidino moiety: induction of production of fetal hemoglobin in human erythroid precursor cells.
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.
authors.affiliation: BioPharmaNet, Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, Ferrara, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Bianchi
authors.forename: Monica
authors.initials: M
authors.lastname: Borgatti
authors.forename: Eitan
authors.initials: E
authors.lastname: Fibach
authors.forename: Eugenia
authors.initials: E
authors.lastname: Prus
authors.forename: Cristina
authors.initials: C
authors.lastname: Zuccato
authors.forename: Giulia
authors.initials: G
authors.lastname: Breveglieri
authors.forename: Pier Giovanni
authors.initials: PG
authors.lastname: Baraldi
authors.forename: Romeo
authors.initials: R
authors.lastname: Romagnoli
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D004214:Distamycins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005319:Fetal Hemoglobin / Q000378:metabolism*; D006401:Hematologic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells; D012333:RNA, Messenger / Q000235:genetics; D013329:Structure-Activity Relationship; D017086:beta-Thalassemia / Q000188:drug therapy; D055545:gamma-Globins / Q000235:genetics / Q000378:metabolism
chemical_list: D004214:Distamycins; D006401:Hematologic Agents; D012333:RNA, Messenger; D055545:gamma-Globins; C030000:stallimycin; D005319:Fetal Hemoglobin