Nucleoside Antimetabolite/Analog

Nucleoside analogues are molecules that act like nucleosides in DNA synthesis. They include a range of antiviral products used to prevent viral replication in infected cells. Nucleoside analogues can be used against hepatitis B virus, hepatitis C virus, herpes simplex, and HIV.

121032-29-9
Nelarabine
121032-29-9
122111-03-9
122111-03-9
123318-82-1
Clofarabine
123318-82-1
147-94-4
Cytarabine
147-94-4
154361-50-9
Capecitabine
154361-50-9
154-42-7
Thioguanine
154-42-7
17902-23-7
17902-23-7
B0084-424412
Tipiracil HCl
183204-72-0
209799-67-7
Forodesine
209799-67-7
210829-30-4
Gemcitabine elaidate
210829-30-4
21679-14-1
Fludarabine
21679-14-1
284490-13-7
284490-13-7
3094-09-5
Doxifluridine
3094-09-5
320-67-2
Azacitidine
320-67-2
4342-03-4
Dacarbazine
4342-03-4

Background


An Overview of Nucleoside Antimetabolite/Analog

The mechanism of nucleoside analogues is to antagonize nucleotide metabolism in vivo by inhibiting the synthesis of deoxynucleoside triphosphate (dNTPs) and to interfere with cell replication by incorporation of DNA or RNA molecules to competitively inhibit DNA polymerase, specifically interfering with nucleic acid metabolism and preventing cell division and reproduction, leading to tumor cell death. Most of nucleoside analogues are pyrimidines or purines. The three structural and functional groups of nucleotides needed in the process of DNA replication are chemically modified according to the principles of prodrug design and bioelectron arrangement. Most nucleoside analogues are composed of bases and glycosyl groups.

Drug resistance of Nucleoside Antimetabolite/Analog

The antiviral effect of nucleotide analogs is accomplished by specifically binding to one part of HBV (hepatitis B virus) polymerase and causing the DNA strand break of the virus, thus affecting the replication of the virus. In order to survive, the virus replaces the amino acids in certain parts of the HBV polymerase region in replication, that is, the mutation of the virus gene results in a decrease in the adhesion and sensitivity of the drug to the virus. So the inhibitory effect on HBV was decreased or disappeared. Recently, some experts have proposed genetic barrier and pharmacokinetic barrier to explain the production of drug resistance.

Nucleoside Antimetabolite/Analog and diseases

 

Nucleoside Antimetabolite/ Analog have a long history as clinical antiviral and antitumor drugs. The birth of anti-AIDS and viral hepatitis drugs such as zidovudine (AZT) and lamivudine has important application value for the treatment of such diseases. The mechanism of action of nucleoside drugs is mainly to simulate natural nuclei. Glycosides inserted into the DNA or RNA strands of viruses or tumor cells cut off the extension or competitive inhibition of nucleotide polymerase, interfere with the biosynthesis of nucleic acids and proteins, and play an antiviral and antitumor role. Nucleoside antiviral drugs are mainly enzyme inhibitors and DNA chain terminators. This class of nucleoside antiviral drugs is mainly used for the treatment of HIV, hepatitis virus, herpesvirus and Ebola virus infection.

Reference:

1. Su Rong, Yang Yanbin, Huang Wanlin, Luo Na, he Xian. Detection and Analysis of nucleoside Analog Resistance in 100 patients with Hepatitis B in Guangdong Province [J]. Modern Preventive Medicine! 43 (06): 1092-1096.