New uracil dimers showing erythroid differentiation inducing activities.
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.
Accetta
Alessandro
A
Dipartimento di Chimica Organica ed Industriale, Universita degli Studi di Parma, Parma, Italy.
Corradini
Roberto
R
Sforza
Stefano
S
Tedeschi
Tullia
T
Brognara
Eleonora
E
Borgatti
Monica
M
Gambari
Roberto
R
Marchelli
Rosangela
R
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*
D014498:Uracil