Synthesis and antiretroviral evaluation of derivatives of zidovudine

Journal of the Brazilian Chemical Society

Trinchero-Hernández, Juan S.¹  Turk, Gabriela¹  Universidad de Buenos Aires, Buenos Aires, Argentina¹  Universidad Nacional de Córdoba, Córdoba, Argentina¹  Briñón, Margarita C.¹  Raviolo, Mónica A.¹ 

关键词: zidovudine analogs;    anti-HIV activity;    cytotoxicity;   

DOI  :  10.1590/S0103-50532009001000015

学科分类：化学（综合）

来源: SciELO

【 摘 要 】

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.

【 授权许可】

Unknown