Synthesis of phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides: novel inhibitors of reverse transcriptase.
Phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides have been synthesized in good yields by 1,3-dipolar cycloaddition methodology. The cytotoxicity and the reverse transcriptase inhibitory activity of the obtained compounds have been investigated. Phosphonated carbocyclic 2'-oxa-3'-aza-nucleosides, while showing low levels of cytotoxicity, exert a specific inhibitor activity on two different reverse transcriptases, which is comparable with that of AZT, opening new perspectives on their possible use as therapeutic agents, in anti-retroviral and anti-HBV chemotherapy.
Chiacchio
Ugo
U
Dipartimento Farmaco-Chimico, Università di Messina, Via SS. Annunziata, Messina 98168, Italy.
Balestrieri
Emanuela
E
Macchi
Beatrice
B
Iannazzo
Daniela
D
Piperno
Anna
A
Rescifina
Antonio
A
Romeo
Roberto
R
Saglimbeni
Monica
M
Sciortino
M Teresa
MT
Valveri
Vincenza
V
Mastino
Antonio
A
Romeo
Giovanni
G
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology; D009589:Nitrogen Oxides / Q000737:chemistry; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D001372:Aza Compounds; D009589:Nitrogen Oxides; D009705:Nucleosides; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; C015388:nitrones