MEDICINAL CHEMISTRY OF ANTIVIRAL AGENTS
T.SOUJANYA
PHARM-D
ANTI VIRAL AGENTS:Anti viral drugs are a class of medication used specifically for
treating viral infections.Viruses are obligate intracellular
parasites,smallest of all self replicating organisms,able to pass through
filter that retain the smallest bacteria.Virus conduct no metabolic
process on their own.They invade the host cell which may be
bacteria,animal or plant cell.
STRUCTURE OF VIRUS:Virus doesn’t possess cell
wall.It consists of one or more of
linear or helical strands pf either
DNA or RNA,enclosed in the
shell of protein known as
capsid.The capsid is composed of
several sub units known as
capsomers.In certain
cases,capsid may be surrounded
by an outer protein or
lipoprotein envelop.
LIFE CYCLE OF VIRUS:Viral life cycle varies with species but they all share a general pattern.
1.Adsorption:-Attachment of virus to the host cell.
2.Penetration:-Penetration of virus into the host cell.
3.Uncoating:-The genetic material of viral genome(DNA/RNA)passes into the
host cell, leaving the capsid covering outside the cell.
4.Transcription:-Production of viral m-RNA from viral genome.
5.Translation:-Viral genome enters the cytoplasm or nucleoplasm and utilises
the host nucleic acid for the synthesis of new viral protein and also for the
production of more viral genome.The viral protein modifies the host cell and
allows the viral genome to replicate by using host and viral enzyme.In this
stage,the cell is irreversibly modified and eventually killed.
6.Assembly:-New viral coat protein assembles into capsid and viral
genomes.
7.Release:-Release of the mature virus from the cells by budding
process or by rupture of the cell and the process is repeated in fresh
host cell.Since the host cell machinery is totally utilised for the
production of new virions,the normal cell function ceases at the time
of production.
CLASSIFICATION
CLASSIFICATION OF ANTI VIRAL AGENTS:The anti viral agents may be divided into the following categories
based on their chemical structure:1.Admantane derivatives:Amantadine,Rimantadine,Somantadine,Tromantadine
2.Purine nucleotides:Acyclovir,Ganciclovir,Vidarabine,Valaciclovir,Penciclovir
3.Pyrimidine nucleotides:Trifluridine,Idoxuridine
4.Phosphorus derivatives:Foscarnet
1.ADMANTANE DERIVATIVES:a)Amantadine
b)Rimantadine
c)Somantadine
d)Tromantadine
2.PURINE NUCLEOTIDES:a)Acyclovir
b)Ganciclovir
c)Vidarabine
d)Valaciclovir
e)Penciclovir
3.PYRIMIDINE NUCLEOTIDES:a)Trifluridine
b)Idoxuridine
4.PHOSPHORUS DERIVATIVES:Foscarnet
SYNTHESIS
1.SYNTHESIS OF AMANTADINE:-
PROPERTIES & USES:Amantadine is a white,odourless,crystalline powder with a bitter
taste,freely soluble in water.It is effective in the prophylaxis and therapy
of infection caused by influenza-A and is active against a number of DNA
and RNA virus in vitro.It may block either the assembly of influenza-A
virus or the release of viral nucleic acid in the host cell.
The drug is well absorbed from the GIT is not metabolised and
is excreted by the kidney.
Dose related adverse effects include
confusion,hallucinations,seizures & coma.
2.SYNTHESIS OF RIMANTADINE:-
3.SYNTHESIS OF TROMANTADINE:-
4.SYNTHESIS OF ACYCLOVIR:-
Acyclovir
MECHANISM OF ACTION:Acyclovir gets activated after three phosphorylation steps by
viral specific enzymes termed thymidine kinases.These active
metabolites accumulate in the infected cells and exerts their action by
two mechanisms.
1.Competitive inhibition of herpes virus DNA polymerases.
2.Incorporation of Acyclovir into viral DNA.
SAR OF ACYCLOVIR:-
1.The length of acyclic side chain attached at N-9 is essential for the anti
viral activity.
2.When the acyclic side chain containing hydroxy methylene group was
replaced by other substituents,inactive analogues are obtained.This
implies that –CH2OH group is essential for anti viral activity.
3.The 9-alkoxy derivative was obtained when a slight modification was
brought in the acyl side chain which is highly active against herpes
simplex and varicella zoster viruses.
4.Several structural modifications have been brought to acyclovir to
obtain high potent drugs.
USES OF ACYCLOVIR:It is a drug of choice in both prophylaxis and treatment of
herpes simplex virus,particularly type-1 including chronic and recurrent
mucocutaneous herpes in the immunologically impaired host,primary
and secondary genital herpes and herpes simplex encephalitis.Cells
infected with herpex simplex phosphorylate the drug to yield a
cycloguanosine triphosphate,which preferentially inhibits viral DNA
polymerase.
5.SYNTHESIS OF TRIFLURIDINE:-
Trifluridine
6.SYNTHESIS OF IDOXURIDINE:-
Idoxuridine
MECHANISM OF ACTION:1.Idoxuridine acts as a anti viral agent against DNA virus.
2.It is phosphorylated by thymidine kinase to active triphosphate.
3.This phosphorylated drug inhibits HSV DNA polymerase enzyme
which is necessary for the synthesis of viral DNA.
4.The ability of idoxuridylic acid substitute for deoxythymidic acid in the
synthesis of viral DNA may be due to the similar vander waal’s radii of
iodine and the thymidine methyl group.
USES OF IDOXURIDINE:Idoxuridine is mainly used for the topical treatment of HSV
infection of eyelid,conjuctiva & cornea and approved as opthalmic
ointment or solution.Epithelial infections respond much better than
stromal infections.
SUMMARY MOA OF ANTI VIRAL AGENTS:-