Zidovudine, also known as AZT, is a clinically important antiretroviral drug.
I. Introduction. zidovudine, chemical name 3'-azido-3'-Deoxythymidine, a nucleoside analogue, belongs to the class of antiretroviral drugs. Since it was approved for AIDS in 1987, zidovudine has been one of the important antiretroviral drugs. The purpose of this article is to provide a comprehensive overview of the research progress in the chemical structure, mechanism of action, pharmacokinetics and clinical application of zidovudine.
2. Chemical structure and synthesis.
The chemical structure of zidovudine consists of a pyrimidine ring and a pentose ring, 3 on the pyrimidine ring'- The position is replaced by an azide group, which prevents the further extension of the DNA polymerase. Its synthesis methods mainly include direct synthesis and solid-phase synthesis. The direct synthesis method usually uses pyrimidine nucleoside as the starting material, and zidovudine is obtained through a series of chemical reactions. The principle of solid-phase synthesis is to attach a nucleoside analogue to a resin to obtain the target molecule through a series of chemical reactions.
3. Mechanism of action.
The mechanism of action of zidovudine is mainly by inhibiting reverse transcriptase activity, thereby preventing the synthesis of viral DNA. When zidovudine enters the cell, it is phosphorylated into an active triphosphate form that competitively binds to the natural substrate deoxythymidine, thereby inhibiting reverse transcriptase activity and preventing viral DNA synthesis. In addition, zidovudine can also induce cells to produce some immunomodulatory molecules, thereby enhancing the body's immune function.
4. Pharmacokinetics.
Zidovudine is well absorbed orally, and the peak blood concentration is reached 1-2 hours after taking the drug. Zidovudine is mainly metabolized in the liver, and metabolites include inactive N-deoxy-zidovudine and active deoxy-zidovudine. About 30% of the drug is excreted from the kidneys in its original form, and the rest is excreted in the form of metabolites.
5. Clinical application.
Zidovudine is one of the first-line drugs for AIDS and AIDS-related syndromes. In addition, zidovudine is also used for certain cancers and autoimmune diseases. However, because long-term use of zidovudine may lead to adverse effects such as bone marrow suppression and abnormal liver function, patients need to be closely monitored for liver function and hemograms.
6. Prospects. Although zidovudine is a highly effective antiretroviral drug, new drugs need to be continuously developed to address these challenges as the virus mutates and drug resistance emerges. At present, a number of new antiretroviral drugs have been developed that have higher antiviral activity and lower rates of drug resistance. In the future, with the continuous progress of science and technology and the continuous emergence of new drugs, it is believed that mankind will be able to defeat major infectious diseases such as AIDS.