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Zalcitabine (Molecule of the Month for April 2007)

2'-3'-dideoxycytidine, ddC, Hivid



Zalcitabine is a nucleoside analog reverse transcriptase inhibitor (NARTI). When HIV infects a cell, reverse transcriptase copies the viral single stranded RNA genome into a double-stranded viral DNA. The viral DNA is then integrated into the host chromosomal DNA which then allows host cellular processes, such as transcription and translation to reproduce the virus. RTIs block reverse transcriptase's enzymatic function and prevent completion of synthesis of the double-stranded viral DNA thus preventing HIV from multiplying. Zalcitabine appears less potent than some other nucleoside RTIs, has an inconvenient three-times daily frequency and is associated with serious adverse events. For these reasons it is now rarely used to treat human immunodeficiency virus (HIV).

Zalcitabine was developed in the National Cancer Institute (NCI) by Samuel Broder, Hiroaki Mitsuya, and Robert Yarchoan at the National Cancer Institute (NCI). Like didanosine, it was then licensed because the NCI may not market drugs. The National Institutes of Health (HIH) thus licensed it to Hoffman LaRoche.

Zalcitabine is an analog of pyrimidine. It is a derivative of the naturally existing deoxycytidine, made by replacing the hydroxyl group in position 3' with a hydrogen. It is phosphorylated in T cells and other HIV target cells into its active triphosphate form, ddCTP. This active metabolite works as a substrate for HIV reverse transcriptase, and also by incorporation into the viral DNA, hence terminating the chain elongation due to the missing hydroxyl group. Since zalcitabine is a reverse transcriptase inhibitor it possess activity only against retroviruses. Lamivudine (3TC) significantly inhibits the intracellular phosphorylation of zalcitabine to the active form, and accordingly the drugs should not be administered together.

Formal Chemical Name (IUPAC)
4-amino-1-((2R,5S)-5-(hydroxymethyl)tetrahydrofuran-2-yl)pyrimidin-2(1H)-one

References

http://en.wikipedia.org/wiki/Zalcitabine

Picture of Zalcitabine

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Picture of Zalcitabine

C9 H13 N3 O3



Update by Karl Harrison
(Molecule of the Month for April 2007 )