The design, synthesis, and the evaluation of the cytotoxic activity of a novel group of hybrids, namely a mol. combination of the natural antibiotic agent distamycin A and the antimetabolite 5-fluorouracil is reported and structure-activity relationships are discussed. This homologous series [I; n = 1-6] consisted of the oligopeptides distamycin A joined to 5-fluorouracil by aliph. carboxylic acid moieties contg. a polymethylene chain [(CH2)n, where n = 1 up to 6]. In vitro antitumor activity of this new class of derivs. was appreciable for compds. with at least two methylenes I (n = 2-6). For these compds. the in vitro antitumor activity was not influenced by the length of the -[CH2]n linker, being comparable to that of the parent compd. distamycin A. Arrested polymerase-chain expts. demonstrated selective binding of the 5-fluorouracil-distamycin hybrids to A+T rich DNA sequences.

Design, synthesis and biological activity of 5-fluorouracil-distamycin hybrids

BARALDI, Pier Giovanni
Primo
;
ROMAGNOLI, Romeo
Secondo
;
BIANCHI, Nicoletta
Penultimo
;
GAMBARI, Roberto
Ultimo
2001

Abstract

The design, synthesis, and the evaluation of the cytotoxic activity of a novel group of hybrids, namely a mol. combination of the natural antibiotic agent distamycin A and the antimetabolite 5-fluorouracil is reported and structure-activity relationships are discussed. This homologous series [I; n = 1-6] consisted of the oligopeptides distamycin A joined to 5-fluorouracil by aliph. carboxylic acid moieties contg. a polymethylene chain [(CH2)n, where n = 1 up to 6]. In vitro antitumor activity of this new class of derivs. was appreciable for compds. with at least two methylenes I (n = 2-6). For these compds. the in vitro antitumor activity was not influenced by the length of the -[CH2]n linker, being comparable to that of the parent compd. distamycin A. Arrested polymerase-chain expts. demonstrated selective binding of the 5-fluorouracil-distamycin hybrids to A+T rich DNA sequences.
2001
Baraldi, Pier Giovanni; Romagnoli, Romeo; Martinez, A; Pineda de las Infantas, M. J.; Gallo, M. A.; Espinosa, A; Rutigliano, C; Bianchi, Nicoletta; Ga...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/1690933
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