Enantioselective syntheses and cytotoxicity of N,O-nucleosides.
Enantiomers of 4'-aza-2',3'-dideoxynucleosides have been prepared by two different synthetic approaches, on the basis of 1,3-dipolar cycloaddition of a chiral nitrone. Cytotoxicity and apoptotic activity have been investigated. (5'S)-5-Fluoro-1-isoxazolidin-5-yl-1H-pyrimidine-2,4-dione [(-)-AdFU], while showing low level of cytotoxicity, is a good inductor of apoptosis on lymphoid and monocytoid cells, acting as a strong potentiator of Fas-induced cell death.
Chiacchio
Ugo
U
Dipartimento di Scienze Chimiche, Università di Catania, Viale Andrea Doria 6, Catania 95125, Italy. uchiacchio@dipchi.unict.it
Corsaro
Antonino
A
Iannazzo
Daniela
D
Piperno
Anna
A
Pistarà
Venerando
V
Rescifina
Antonio
A
Romeo
Roberto
R
Valveri
Vincenza
V
Mastino
Antonio
A
Romeo
Giovanni
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity; D017209:Apoptosis; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D008221:Lymphoid Tissue / Q000166:cytology; D008968:Molecular Conformation; D009000:Monocytes / Q000166:cytology; D011789:Quantum Theory; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D014529:Uridine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D019014:fas Receptor / Q000502:physiology
C476985:5-fluoro-1-isoxazolidin-5-yl-1H-pyrimidine-2,4-dione; D000970:Antineoplastic Agents; D000998:Antiviral Agents; D061945:Caspase Inhibitors; D015224:Dideoxynucleosides; D007555:Isoxazoles; D019014:fas Receptor; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D014529:Uridine