Anti-HIV therapy with AZT prodrugs: AZT phosphonate derivatives, current state and prospects.
BACKGROUND
AIDS, a disease caused by human immunodeficiency virus, was called 'plague of the twentieth century'. 3'-Azido-3'-deoxythymidine (AZT), the first compound approved for the treatment of HIV, is still a mandatory component of treatment schemes. However, its toxicity stimulated a search for new agents.


METHODS
This review presents the history and current state of the design of AZT prodrugs based on its phosphonate derivatives.


RESULTS
Although every effort was made to include as many AZT structures bearing phosphonate residues and demonstrate the variety they offer, we also concentrated on the studies performed in our laboratory. Special attention was also paid to AZT 5'-H-phosphonate (phosphazide, Nikavir) approved in the Russian Federation as a drug for the prevention and treatment of HIV infection.


CONCLUSIONS
The prodrug strategy applied to AZT phosphonate derivatives enriched chemistry, biology and medicine not only with new knowledge, methods and structures, but also with a new anti-HIV drug Nikavir. Currently, study of another phosphonate, AZT 5'-aminocarbonylphosphonate, is underway. Slow release of AZT following oral administration and penetration into cells, decreased toxicity and the lack of cumulative properties make the compounds of this group promising as extended-release forms of AZT.
Khandazhinskaya
Anastasiya
A
Engelhardt Institute of Molecular Biology, Vavilov 32, Moscow, Russian Federation. lhba-imb@mail.ru
Matyugina
Elena
E
Shirokova
Elena
E
D000818:Animals; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D063065:Organophosphonates / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D011355:Prodrugs / Q000494:pharmacology / Q000627:therapeutic use*; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity
D063065:Organophosphonates; D011355:Prodrugs; D015215:Zidovudine