title: New uracil dimers showing erythroid differentiation inducing activities.
abstract: The synthesis of C5 linked uracil dimers was carried out according to a model developed in order to bind adenine in DNA. N1-Alkylated uracil derivatives were synthesized from isoorotic acid (uracil-5-carboxylic acid) or thymine. The carboxylic acid derivatives were condensed with diamines in order to produce dimeric compounds or with monoamines in order to obtain reference monomeric compounds. Some of the derivatives, in particular the uracil dimers, showed antiproliferative and erythroid differentiation induction properties towards human chronic myelogenous leukemia K562 cells, thus indicating that these compounds could represent a new class of drugs useful for the development of antitumor therapy based on the ability to induce terminal differentiation.
authors.affiliation: Dipartimento di Chimica Organica ed Industriale, Universita degli Studi di Parma, Parma, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Accetta
authors.forename: Roberto
authors.initials: R
authors.lastname: Corradini
authors.forename: Stefano
authors.initials: S
authors.lastname: Sforza
authors.forename: Tullia
authors.initials: T
authors.lastname: Tedeschi
authors.forename: Eleonora
authors.initials: E
authors.lastname: Brognara
authors.forename: Monica
authors.initials: M
authors.lastname: Borgatti
authors.forename: Roberto
authors.initials: R
authors.lastname: Gambari
authors.forename: Rosangela
authors.initials: R
authors.lastname: Marchelli
mesh_terms: D000478:Alkylation; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019281:Dimerization; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D041905:Erythroid Cells / Q000166:cytology* / Q000187:drug effects*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014498:Uracil / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D014498:Uracil