Zidovudine (INN) or azidothymidine (AZT) (also called ZDV) is a nucleoside analog reverse-transcriptase inhibitor (NRTI), a type of antiretroviral drug used for the treatment of HIV/AIDS. It is an analog of thymidine.
AZT was the first approved treatment for HIV, sold under the names Retrovir and Retrovis. AZT use was a major breakthrough in AIDS therapy in the 1990s that significantly altered the course of the illness and helped destroy the notion that HIV/AIDS was a death sentence. AZT slows HIV spread significantly, but does not stop it entirely. This allows HIV to become AZT-resistant over time, and for this reason AZT is usually used in conjunction with other NRTIs and anti-viral drugs. In this form, AZT is used as an ingredient in Combivir and Trizivir, among others. Zidovudine is included in the World Health Organization's "Essential Drugs List", which is a list of minimum medical needs for a basic health care system.[2]
Replies
Preying on the weak is just sinful one should not use any drugs without first consulting ones doctor. The idiot that sells drugs on maoliworld is a coward and wants to make money of people who are dying and lonely to add to the problem.
This drug seller is not only a criminal but have no remorse to the injury that he is inflicting upon people that are sick!!!!
The rapid spread of the previously unknown infectious disease acquired immuno
deficiency syndrome (AIDS) has caused a worldwide concern for fighting this
disease effectively. AIDS has been conclusively shown to be caused by the human
immuno deficiency virus (HIV) by Gallo et al (1984) and since then researchers have
been engaged in carrying out various studies to understand the life cycle of HIV, its
structure and functions (Vogel et al 1988; Lapatto et al 1989; Malim et al 1989;
Pang et al 1990). At the same time the search is on to find an effective drug to
combat AIDS. The antiviral agent, 3'-azido-3'-deoxythymidine or simply,
azidothymidine (AZT) has shown great promise in inhibiting HIV replication in
vitro (Mitsuya et al 1985) and in reducing the mortality in AIDS patients in vivo
(Mitsuya and Broder 1987; Yarchoan and Broder 1987; Yarchoan et al 1988). The
exact mechanism of AZT's antibiotic action is not yet fully established but there is
enough evidence to suggest that AZT inhibits the binding of thymidylate to reverse
transcriptase (Ono et al 1986) and that AZT may be incorporated in place of
thymidine into viral DNA and thereby terminate the DNA chain elongation (St.
Clair et al 1985). AZT is phosphorylated to its 5'-triphosphate by cellular enzymes
which specifically interact with reverse transcriptase (Furman et al 1986). However,
AZT has caused serious toxicity problems in many AIDS patients (Kolata 1987)
and hence there is an urgent need for efficient and less toxic drugs for AIDS.
X-ray crystallographic studies on AZT have been first reported by Camerman et
al (1987) and their results indicate that there are two independent molecules of AZT
in the asymmetric unit cell. The sugar ring puckering in molecule A is C2'-endo,
C3'-exo and that in molecule Β is C3'-exo, C4'-endo. The glycosyl torsion angle χCN
*Corresponding author.
2930 Anil Saran and R Ρ Ojha
Figure 1. Schematic diagram of AZT and thymidine showing the various torsion angles.
(see figure 1) is anti for both molecules of AZT: χCN = 52·9° for AZT-molecule A
and 3·5° for AZT-molecule B. The conformation around the exocyclic C4'-C5' bond
is gg(φ C4'-C5' = 50·7°) in AZT-molecule A while for molecule Β it is gt(φ C4'-C5'
= 173·6°). An independent X-ray crystallographic study on AZT has also been
reported by Parthasarathy and Kim (1988) which indicates almost identical results
to those reported by Camerman et al (1987). Camerman, et al (1987) compared the
crystal conformation of AZT molecules A and Β with those of thymidine 3'-
phosphate moieties A and Β of a highly hydrated crystal structure of the
dinucleotide, 5'-phosphothymidylyl (3'-5') thymidine reported earlier by Camerman
et al (1976). Although the two structures are grossly similar in nature to each other,
they differ considerably in details. Evidence of this is in the differences between the
torsion angles observed in the two structures and this is particularly true for the
structure of AZT-molecule B. Camerman et al (1987) have also shown diagrams
speculating the possible binding of AZT and thymidylate with reverse transcriptase
based on the crystal conformations of AZT and thymidylate resulting in DNA
chain termination. Their arguments are, however, highly speculative in nature.
Firstly, there is no guarantee that the crystal conformations of AZT as observed in
the solid state would be preserved exactly in aqueous solution at physiological pH
and this is at least true for molecules of the size of AZT or thymidylate. For very
large biomolecules such as nucleic acids and proteins where the crystal packing
forces and environmental factors cannot dictate the conformation, the agreement
between the X-ray structures and the solution conformations is very good.
Secondly, the crystal structure of thymidylate utilized for comparison with that of
AZT is not on the mononucleotide itself but on a dinucleotide, d(pTpT) and the
conformation of mononucleotide in the solid state may not be the same as that of
the dinucleotide. Therefore, the comparison between AZT and thymidylate may not
be strictly valid.
Swapna et al (1989) studied the conformation of AZT by proton and carbon-13
NMR in solution and their results indicate that the sugar pucker exists in C2'-endo
and C3'-endo equilibrium. The glycosyl torsion angle is anti and the conformation Conformation of azidothymidine 31
around C4'-C5' bond is predominantly gg. These solution results are obviously at
variance with those obtained in the solid state from X-ray crystallography. These
authors also reported very briefly the predominance of gg conformation around
C4'-C5' for both molecules of AZT by the PCILO method. Molecular mechanics
studies on the conformation of AZT molecule carried out by Herzyk et al (1987)
indicate that AZT has C3'-endo sugar pucker and the conformations around the
glycosyl and C4'-C5' bonds are, respectively, anti and gg. These authors have also concluded that AZT has no unusual features but has conformational properties that are
very similar to those of standard deoxypyrimidines. These results on AZT are, clearly,
at variance with those obtained in the solid state from X-ray crystallography.
The conformation of nucleoside antibiotics has been investigated in our
laboratory for several years (Saran 1981, 1987, 1989) and these studies have
established an important correlation between the conformation and biological
activity of nucleoside antibiotics. AZT is a nucleoside antibiotic which results as a
consequence of the replacement of 3'-hydroxyl group of the parent nucleoside,
thymidine, by an azido group (figure 1). We have in the present study carried out an
extensive and detailed PCILO investig