Synthesis and antiretroviral evaluation of derivatives of zidovudine

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, t...

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Bibliographic Details
Published in:Journal of the Brazilian Chemical Society 2009, Vol.20 (10), p.1870-1877
Main Authors: Raviolo, Mónica A., Trinchero-Hernández, Juan S., Turk, Gabriela, Briñón, Margarita C.
Format: Article
Language:English
Subjects:
CHEMISTRY, MULTIDISCIPLINARY
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Summary: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.
ISSN:0103-5053
1678-4790
DOI:10.1590/S0103-50532009001000015