Synthesis and antiretroviral evaluation of derivatives of zidovudine

• Autor(a) principal: Raviolo,Mónica A.
• Data de Publicação: 2009
• Outros Autores: Trinchero-Hernández,Juan S., Turk,Gabriela, Briñón,Margarita C.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Journal of the Brazilian Chemical Society (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532009001000015
• topic: zidovudine analogs; anti-HIV activity; cytotoxicity

A series of zidovudine (AZT, 1) derivatives have been synthesized and their anti-HIV activity and cytotoxicity have been determined. The 5'-OH function of AZT was derivatized using N, N'-carbonyldiimidazole and different amine compounds leading to their 5'-O-carbamates. In addition, two known AZT derivatives 5'-O-tosylate and a tricyclic one (AZT-Cycl) were also obtained by a simpler procedure than those previously reported. Although these AZT derivatives were less toxic than AZT, their reduced cytotoxicity was concomitant with an inability to inhibit HIV-1 replication, except in the case of AZT-Cycl, which showed an IC50 = 1 µmol L-1 without cytotoxicity with values of CCID50 ( µmol L-1) > 1000.