What type of drug is AZT?
Zidovudine (AZT) is a pyrimidine synthetic analogue active against human immunodeficiency virus type 1 (HIV-1). It belongs to the class of nucleoside reverse transcriptase inhibitors (NRTIs). Monotherapy with AZT is recommended only in the initial management of HIV-1 infected patients.
What is the mechanism of action of AZT?
AZT is one such drug, by mimicking the nucleotide thymidine, it can it can act as a substrate for nucleotide kinases and become 5' phosphorylated. AZT is phosphorylated by host cell enzymes, specifically thymidine kinase, this means that the levels of AZT phosphates are similar between HIV infected and non-infected cells.
What is a nucleophilic species?
Therefore, nucleophiles can be thought of as Nucleus Loving species. These nucleophiles may have either a negative, or a neutral charge. Some terminologies regarding nucleophiles are discussed below. The nucleophilic nature of a species describes the affinity of the species to the positively charged nucleus.
What is the difference between AZT and HIV?
While AZT is effective in inhibiting viral replication, HIV is capable of mutating and thus of developing resistance to the drug. As a result, it is often given, either orally or intravenously, in combination with at least two or three other drugs in order to overcome drug resistance. Patients receiving combination therapy with AZT...
Is AZT electrophilic?
Such behavior indicates the capability of AZT to undergo electrophilic interactions through its terminal azido substituents, especially the middle N atom.
What type of inhibitor is AZT?
AZT is an analog of the thymidine deoxynucleoside and is a member of the class called the nucleoside-analog reverse transcriptase inhibitors. AZT and other members of this class function by inhibiting the HIV reverse transcriptase. This halts the life cycle of the virus and slows the progression of AIDS.
What is the functional mechanism of AZT?
Mechanism of action AZT works by selectively inhibiting HIV's reverse transcriptase, the enzyme that the virus uses to make a DNA copy of its RNA.
What is AZT in chemistry?
The full form of AZT is azidothymidine which is also called as zidovudine is a type of drug which is used to delay the development of AIDS in the patients which are affected by HIV(human immunodeficiency virus). The group of drugs from where AZT belongs is known as nucleoside reverse transcriptase inhibitors.
Is AZT classified as an antibiotic or antiviral drug?
Antiviral drug azidothymidine 63, known also as AZT and zidovudine, is useful in treatment of AIDS as an agent impeding the human immunodeficiency virus replication process.
What feature of AZT makes it an effective inhibitor of reverse transcriptase?
This is because the active compound of AZT, known as zidovudine 5-triphosphate, has a high affinity (attraction) for an enzyme called reverse transcriptase, which is used by retroviruses such as HIV to replicate viral single-stranded RNA (ribonucleic acid) into proviral double-stranded DNA (deoxyribonucleic acid).
How does AZT block reverse transcriptase?
0:001:46How the drug AZT blocks HIV reverse transcriptase - YouTubeYouTubeStart of suggested clipEnd of suggested clipNow let's see how azt works here's the rna and the reverse transcriptase. Again the purple piecesMoreNow let's see how azt works here's the rna and the reverse transcriptase. Again the purple pieces are host cell nucleotides being assembled into a dna strand. The green molecule is azt.
What class of drug is zidovudine?
Zidovudine is in a class of medications called nucleoside reverse transcriptase inhibitors (NRTIs). It works by decreasing the amount of HIV in the blood.
Does AZT affect human DNA replication?
1 AZT causes replication inhibition and SOS induction via accumulation of single-strand DNA gaps. If AZT causes DNA damage by inhibiting replication fork progression, replication should stop or slow when cultures are treated with AZT.
How does AZT stop DNA replication?
After being activated by phosphorylation in vivo, AZT inhibits HIV replication by blocking a critical HIV enzyme called reverse transcriptase. This enzyme uses the virus's RNA genome as a template to build a DNA version that can be inserted into the host's genome.
What was AZT originally used for?
AZT, or azidothymidine, was originally developed in the 1960s by a U.S. researcher as way to thwart cancer; the compound was supposed to insert itself into the DNA of a cancer cell and mess with its ability to replicate and produce more tumor cells.
How does AZT block reverse transcriptase?
0:001:46How the drug AZT blocks HIV reverse transcriptase - YouTubeYouTubeStart of suggested clipEnd of suggested clipNow let's see how azt works here's the rna and the reverse transcriptase. Again the purple piecesMoreNow let's see how azt works here's the rna and the reverse transcriptase. Again the purple pieces are host cell nucleotides being assembled into a dna strand. The green molecule is azt.
What is a protease inhibitor and how does it work?
Medications that inhibit the cleavage of the polyprotein into functional proteins are called protease inhibitors. Protease is a protein-based enzyme that normally breaks the polyprotein into functional proteins, so blocking, or inhibiting, protease prevents this essential step of viral reproduction.
What was AZT originally used for?
AZT, or azidothymidine, was originally developed in the 1960s by a U.S. researcher as way to thwart cancer; the compound was supposed to insert itself into the DNA of a cancer cell and mess with its ability to replicate and produce more tumor cells.
Is Abacavir a protease inhibitor?
5.07. The majority of antivirals for controlling human immunodeficiency virus (HIV) infection are nucleoside reverse transcriptase inhibitors (AZT, abacavir, lamivudine), nonnucleoside reverse transcriptase inhibitors (nevirapine, efavirenz), HIV protease inhibitors (ritonavir), or integrase inhibitors (elvitegravir).
How effective is AZT?
While AZT is effective in inhibiting viral replication, HIV is capable of mutating and thus of developing resistance to the drug. As a result, it is often given, either orally or intravenously, in combination with at least two or three other drugs in order to overcome drug resistance. Patients receiving combination therapy with AZT or with other NRTIs are closely monitored to determine when the efficacy of the drugs decreases. Such monitoring is often done by periodic measurements of plasma HIV RNA concentrations. Detectable increases in plasma levels of HIV RNA are used as the basis for initiation of AZT therapy to slow the progression of HIV infection. The ability of AZT to suppress viral load (the concentration of virus in the blood) also makes it particularly effective in preventing transmission of HIV from infected pregnant women to their fetuses.
When was AZT approved?
In 1987 AZT became the first of these drugs to be approved by the U.S. Food and Drug Administration for the purpose of prolonging the lives of AIDS patients. AZT is only active against HIV when the virus is replicating into proviral DNA (viral DNA synthesized prior to integration into host DNA).
What enzyme is used to replicate viral single stranded RNA?
This is because the active compound of AZT, known as zidovudine 5-triphosphate, has a high affinity (attraction) for an enzyme called reverse transcriptase, which is used by retroviruses such as HIV to replicate viral single-stranded RNA (ribonucleic acid) into proviral double-stranded DNA (deoxyribonucleic acid).
Which has a greater affinity for reverse transcriptase than thymidine triphosphate?
However, zidovudine 5-triphosphate has a greater affinity for reverse transcriptase than thymidine triphosphate, and it contains a nitrogen group (an azide; N 3) in place of the usual nucleoside hydroxyl group (―OH).
What is the drug called that is used to delay the development of AIDS?
Alternative Titles: Retrovir, azidothymidine, zidovudine. AZT, in full azidothymidine, also called zidovudine, drug used to delay development of AIDS (acquired immunodeficiency syndrome) in patients infected with HIV (human immunodeficiency virus).
Does AZT cause nausea?
AZT also suppresses the production of red blood cells, neutrophils, and other cells in the bone marrow, causing symptoms such as fatigue, malaise, and anemia, and many patients taking AZT experience mild gastrointestinal intolerance, which may cause nausea and vomiting.
Does AZT help with HIV?
The ability of AZT to suppress viral load (the concentration of virus in the blood) also makes it particularly effective in preventing transmission of HIV from infected pregnant women to their fetuses. Get a Britannica Premium subscription and gain access to exclusive content. Subscribe Now.
Summary
AZT is a type of anti-HIV drug called a nucleoside analogue (“nuke”). The most common side effects of AZT can include headache, nausea, and loss of appetite. More rarely, it can cause anemia and low white blood cell counts. It is usually taken at a dose of 300 mg twice daily, with or without food.
What is AZT?
AZT (zidovudine), sold under the brand name Retrovir, is a type of anti-HIV (antiretroviral) drug called a nucleoside analogue or “nuke.” AZT is used in combination with other anti-HIV drugs to treat (but not cure) HIV.
How does AZT work?
To explain how AZT works, we need to first tell you some information about HIV. When HIV infects a cell, it takes control of that cell. HIV then forces the cell to make many more copies of the virus. To make these copies, the cell uses proteins called enzymes. When the activity of these enzymes is reduced the production of HIV slows.
How do people with HIV use AZT?
AZT is used in combination with several other anti-HIV drugs, usually including drugs from different classes, such as protease inhibitors and/or non-nukes (non-nucleoside reverse transcriptase inhibitors). Combinations such as this are called antiretroviral therapy, or ART. For more information on ART, see CATIE's Your Guide to HIV Treatment.
Women and childbirth
AZT is also used to help prevent the transmission of HIV from mother to child during pregnancy and childbirth. It was the first drug studied for this purpose and remains a cornerstone of this kind of prevention, although other drugs have also been investigated.
Warnings
AZT can be toxic to the bone marrow—the soft tissue inside bones where blood cells are made. As a result, AZT can cause anemia (lowered red blood cell levels) and neutropenia (lowered neutrophil or white blood cell counts). In serious cases, this can require blood transfusions, and AZT must be stopped.
Side effects
Common side effects that have been reported by some AZT users include headaches, nausea, vomiting, insomnia, tiredness, muscle pain, and loss of appetite. Many people find that side effects caused by anti-HIV drugs improve or go away after the first several weeks of treatment.
When was AZT approved?
Keeping that in view, AZT was synthesized by Jerome Horwitz in 1964 and was later shown active against HIV and was approved by FDA in 1987 for use against HIV and AIDS. AZT was screened against pathogenic bacteria to assess its antibacterial potential.
What is the name of the compound that blocks nucleic acid synthesis?
26 Zidovudine. Zidovudine or azidothymidine (AZT) is azide analog of deoxythymidine; 3′-azido-3′-deoxythymidine. Compounds that are able to block nucleic acid synthesis such as purine and pyrimidine nucleoside analogs are proven antibacterial, antiviral, and anticancer agents.
What is zidovudine made of?
Zidovudine is 3′-azido-3′-deoxytimidine (36.1.26), is synthesized from 1- (2′-deoxy-5′-O-trityl-β - d -lyxosyl)thymine, which is treated with methansulfonyl chloride in pyridine to make the corresponding mesylate 36.1.24.
What is zalcitabine 9?
Zalcitabine ( 9) is a pyrimidine nucleoside that inhibits replication of HIV-1 in a similar mechanism to 7. Mutation at codon 65 induces resistance which is associated with the decrease in susceptibility to 8 and 9. Sign in to download full-size image.
Is AZT as effective as trimethoprim?
coli pyelonephritis, and Salmonella dublin salmonellosis in calves. In murine systemic E. coli infection model, AZT was as effective as trimethoprim. In murine acute ascending E. coli pyelonephritis model, AZT was as efficacious as ampicillin. The survival rate of calves infected with S. dublin increases when treated with AZT as compared to untreated control. The infection with S. dublin can be correlated with that of S. typhi as both have the same pattern of disease progression [132].
Does 80% acetic acid remove trityl?
Heating this in 80% acetic acid removes the trityl protection, giving zidovudine [ 24–28 ]. Zidovudine is an antiretroviral drug that is clinically active against HIV-1 and is intended to treat HIV-infected patients. Zidovudine is an analog of thymidine that inhibits replication of the AIDS virus.
What Is AZT?
AZT belongs to a class of drugs known as nucleoside reverse transcriptase inhibitors ( NRTIs ). Scientists funded by the NCI developed azidothymidine in 1964 as a potential treatment for cancer and while the drug showed promise at stopping tumor cells from replicating, the drug was deemed largely ineffective and shelved for decades.
What is AZT treatment?
AZT served has since been called the “prototype” for AIDS treatment and is considered a “first step” in the AIDS response, establishing standards and an understanding of viral suppression.
What was Fauci's treatment called?
In September, memes shared widely on Facebook and sent to our staff claimed that at the beginning of his career — which coincided with the onset of the AIDS epidemic — Fauci promoted a controversial treatment called azidothymidine, commonly known as AZT. To discredit the doctor, one such meme claimed that more people died from AZT than did from HIV, the virus that causes the immunodeficient disease.
What did Guccione say about AIDS?
The 1989 article, Guccione continued, “unearthed hard evidence of the cold-bloodedness of the AIDS establishment pushing a drug that was worse than the disease, and killed faster than the natural progression of AIDS left untreated” — both claims that are erroneous. Among other assertations, the article argued that thousands had been “walloped” with high doses of AZT and “possibly even died of toxic poisoning.”
When was the first AZT article written?
But the original article was written in 1989, and in the decades that followed, researchers would deepen their understanding of proper dosing requirements for AZT and how it could be used in combination with other therapies to effectively treat AIDS.
How many deaths were caused by AZT?
It is unknown how many — if any — deaths resulted directly from patients being treated with AZT, as early testing was not always standardized to account for various other experimental and approved treatments, as well as from infection by HIV or other secondary illnesses.
Does AZT kill more people than the virus?
Furthermore, there is no evidence to suggest that the administration of AZT killed more people than the virus itself. It is unknown how many — if any — deaths resulted directly from patients being treated with AZT as early testing was not always standardized to account for various other experimental and approved treatments, as well as from infection by HIV or other secondary illnesses. Today, AZT is still one of more than 30 therapies approved in the United States for the treatment of AIDS.
Why is AZT toxic?
One mechanism for toxicity is the depletion of thymidine, because AZT competes with thymidine for the kinase enzymes, but is phosphorylated at a slower rate. At high doses, >1mM, AZT can act as a substrate for human DNA polymerases.
What is the AZT phosphorylation?
AZT is phosphorylated by host cell enzymes, specifically thymidine kinase, this means that the levels of AZT phosphates are similar between HIV infected and non-infected cells. Once the 5' triphosphate is formed, the drug is a substrate for the viral reverse transcriptase.
What are some examples of nucleotide analogs?
For more information, read about other nucleotide analogs, such as acyclovir, ganciclovir, and others which work through similar mechanisms.
Can cellular repair enzymes remove azidothymidine?
In the last page, the authors suggest that cellular repair enzymes could remove azidothymidine (AZT, zidovudine) from cellular DNA if it's incorporated, but viruses' polymerases lack this ability. As it's an old article, I would like to know if this hypothesis was confirmed.
Is mitochondrial DNA polymerase a reversible molecule?
This toxicity is generally reversible if doses are reduced.
Does AZT stop polymerization?
If someone is not familiar with AZT mechanism: basically, it's an analog of thymidine which has an azide group instead of 3'-OH. It can be phosphorylated by cell kinases and incorporated to the growing DNA chain; however, this will stop the polymerization because it depends on free 3'-OH.
What is the meaning of nucleophilic?
Nucleophilic describes the affinity of a nucleophile to bond with positively charged atomic nuclei. Nucleophilicity, sometimes referred to as nucleophile strength, refers to a substance's nucleophilic character and is often used to compare the affinity of atoms.
What is a nucleophile?
Chemical species that donates an electron pair. In chemistry, a nucleophile is a chemical species that forms bonds with electrophiles by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles.
What is the name of the reaction that occurs when a nucleophile is attracted to a positive charge?
Neutral nucleophilic reactions with solvents such as alcohols and water are named solvolysis. Nucleophiles may take part in nucleophilic substitution, whereby a nucleophile becomes attracted to a full or partial positive charge, and nucleophilic addition. Nucleophilicity is closely related to basicity.
What is an ambident nucleophile?
An ambident nucleophile is one that can attack from two or more places, resulting in two or more products. For example, the thiocyanate ion (SCN −) may attack from either the S or the N. For this reason, the S N 2 reaction of an alkyl halide with SCN − often leads to a mixture of an alkyl thiocyanate (R-SCN) and an alkyl isothiocyanate (R-NCS). Similar considerations apply in the Kolbe nitrile synthesis .
What is the free energy relationship between water and nucleophile?
This free-energy relationship relates the pseudo first order reaction rate constant (in water at 25 °C), k , of a reaction, normalized to the reaction rate, k0, of a standard reaction with water as the nucleophile, to a nucleophilic constant n for a given nucleophile and a substrate constant s that depends on the sensitivity of a substrate to nucleophilic attack (defined as 1 for methyl bromide ).
Who invented the term "nucleophile"?
The terms nucleophile and electrophile were introduced by Christopher Kelk Ingold in 1933, replacing the terms anionoid and cationoid proposed earlier by A. J. Lapworth in 1925. The word nucleophile is derived from nucleus and the Greek word φιλος, philos, meaning friend.
Is sulfur polarizable?
In general, sulfur is very nucleophilic because of its large size, which makes it readily polarizable, and its lone pairs of electrons are readily accessible.
What is a Nucleophile?
Nucleophiles are basically electron rich species which have the ability to donate electron pairs, as discussed earlier. Because of this electron pair donating tendency, all nucleophiles are Lewis Bases.
What is nucleophilicity in biology?
Nucleophilicity is a word used to compare the nucleophilic character of different nucleophiles in question. It can also be called the nucleophile strength of a species. Nucleophilic substitution is a type of reaction that occurs when an electron rich nucleophile selectively attacks a positively charged (or a partially positive charged) ...
What is an ambident nucleophile?
Ambident Nucleophiles. A Nucleophile which can execute nucleophilic attacks from two or more different places in the molecule (or ion) is called an Ambident Nucleophile. Attacks from these types of nucleophiles can often result in the formation of more than one product. An example of an ambident nucleophile is the thiocyanate ion which has ...
What is a type of nucleophilic substitution reaction wherein the nucleophile in question is a?
Solvolysis is a type of nucleophilic substitution reaction wherein the nucleophile in question is a solvent molecule. A good example of such a nucleophilic solvent is water, and the solvolysis with water is often referred to as hydrolysis.
What is the term for a substance that donates electrons to electrophiles?
Nucleophile is a word used to refer to substances that tend to donate electron pairs to electrophiles in order to form chemical bonds with them. Any ion or molecule having an electron pair which is free or a pi bond containing two electrons have the ability to behave like nucleophiles .
What are the nucleophiles of nitrogen?
Nitrogen – Nitrogen is known to form many nucleophiles such as amines, azides, ammonia, and nitrides. Even amides are known to exhibit nucleophilic qualities.
Is an ambident nucleophile an anionic nucleophile?
Therefore, an ambident nucleophile can be thought of as an anionic nucleophile in which the negative charge of the ion is delocalized over two different atoms by resonance effects. Commonly, enolate ions exhibit this quality. An illustration of such a resonance structure of an ambident nucleophile is illustrated below.
What is a nucleophile?
Nucleophilic functional groups are those which have electron-rich atoms able to donate a pair of electrons to form a new covalent bond. In both laboratory and biological organic chemistry, the most relevant nucleophilic atoms are oxygen, nitrogen, and sulfur, and the most common nucleophilic functional groups are water, alcohols, phenols, amines, thiols, and occasionally carboxylates.
Which is the weakest nucleophile?
Now, fluoride is the best nucleophile, and iodide the weakest.
How do nucleophiles attack electrophiles?
In order for the nucleophile to attack the electrophile, it must break free, at least in part, from its solvent cage. The lone pair electrons on the larger, less basic iodi de ion interact less tightly with the protons on the protic solvent molecules - thus the iodide nucleophile is better able to break free from its solvent cage compared the smaller, more basic fluoride ion, whose lone pair electrons are bound more tightly to the protons of the cage.
Why is the reversal of the ion dipoles in aprotic solvents?
The reason for the reversal is that, with an aprotic solvent, the ion-dipole interactions between solvent and nucleophile are much weaker: the positive end of the solvent's dipole is hidden in the interior of the molecule, and thus it is shielded from the negative charge of the nucleophile.
Which is more powerful, thiols or alcohols?
In biological chemistry, where the solvent is protic (water), the most important implication of the periodic trends in nucleophilicity is that thiols are more powerful nucleophiles than alcohols. The thiol group in a cysteine amino acid, for example, is a powerful nucleophile and often acts as a nucleophile in enzymatic reactions, and of course negatively-charged thiolates (RS -) are even more nucleophilic. This is not to say that the hydroxyl groups on serine, threonine, and tyrosine do not also act as nucleophiles - they do.
What is the most common carbon nucleophile?
Enolate ions (section 7.5) are the most common carbon nucleophiles in biochemical reactions, while the cyanide ion (CN -) is just one example of a carbon nucleophile commonly used in the laboratory. Reactions with carbon nucleophiles will be dealt with in chapters 13 and 14, however - in this chapter and the next, ...
Why is the nitrogen atom on an amide less nucleophilic than the nitrogen of an amine?
The nitrogen atom on an amide is less nucleophilic than the nitrogen of an amine, due to the resonance stabilization of the nitrogen lone pair provided by the amide carbonyl group.
