Acyclovir

Cat. No. A030000

CAS. No. 59277-89-3

Acyclovir is a guanine analogue antiviral drug. Its chemical name is 2-amino-9-(2-hydroxyethoxymethyl)-1H-purin-6-one. Its molecular formula is C8H11N5O3 and its molecular weight is 225.20 g/mol. Acyclovir a synthetic analog of the purine nucleoside, guanosine, with potent antiviral activity against herpes simplex viruses type 1 and 2, varicella-zoster virus and other viruses of the herpesvirus family. 

Acyclovir is antiviral class of medications. It is used to treat infections caused by the herpes simplex virus (HSV). It is FDA approved to treat genital herpes and HSV encephalitis. Acyclovir is a new antiviral agent that acts as a specific inhibitor of herpesvirus DNA polymerase. It shows good in vitro activity against herpes simplex and varicella-zoster viruses. 

Acyclovir is used to treat the symptoms of chickenpox, shingles, herpes virus infections of the genitals, the skin, the brain, and mucous membranes (lips and mouth), and widespread herpes virus infections in new-borns. Acyclovir is also used to prevent recurrent genital herpes infections. Acyclovir is available as a capsule, suspension, and buccal tablet you take by mouth. It also comes in a cream and ointment you apply to your skin. In addition, acyclovir is available as an intravenous (IV) drug, which is only given by a healthcare professional.

Acyclovir can be synthesised by alkylating guanine with 1-benzoyloxy-2-chloromethoxyethane in triethylamine. The hydroxyl and amino groups of guanine are protected with a trimethylsilyl group which is treated with hexamethyldisilazane. After hydrolysis the resulting product with water, 9-(2-benzoyloxymethoxymethyl)guanine is isolated. Treating this with a methanol solution of ammonia removes the benzoyl protecting group from the hydroxyethoxymethyl fragment, giving acyclovir.

MECHANSIM OF ACTION: 

Acyclovir is a selective inhibitor of herpes simplex virus replication. It acts as both a substrate for and an inhibitor of viral DNA polymerase, thus blocking DNA synthesis. Acyclovir monophosphate is then further phosphorylated by cellular enzymes (including guanylate kinase) to its triphosphate derivative, which is a potent inhibitor of DNA polymerase.

Acyclovir triphosphate can be found in HSV-infected cells in concentrations 40-100 times higher than that found in uninfected cells. Acyclovir triphosphate inhibits DNA synthesis by competing with doxyguanosine triphosphate for viral DNA polymerase. Viral DNA polymerases exhibit a 10-to-30-fold greater affinity for acyclovir triphosphate than does cellular DNA polymerase. 

The DNA polymerases of HSV-I and HSV-2 utilize the triphosphate derivative as a substrate. Following incorporation of acyclovir triphosphate into the growing DNA chain, DNA synthesis is terminated.

 Non-phosphorylated acyclovir and the monophosphate and diphosphate derivatives do not have any significant inhibitory effect on herpesvirus DNA synthesis.

Among herpesviruses, HSV-1 and HSV-2 and varicella-zoster virus (VZV) is most susceptible to inhibition by acyclovir. Acyclovir is less active against Epstein-Barr virus (EBV) and cytomegalovirus (CMV).

Some of the impurities of Acyclovir are tabulated below: