 GENERAL PROPERTIES

 CHEMISTRY
 BIOLOGICAL ACTION
 THERAPEUTIC APPLICATIONS
 STRUCTURE ACTIVITY RELATIONSHIP
 Class : Anti mycobacterial drug
 White crystalline powder
 Sparingly soluble in water
 Oral route of administration
 Presentation: 500mg tablet
 Stable and inexpensive
 Pregnancy category : C
 Abbreviations : PZA or Z
PZA is the pyrazine analogue of nicotinamide .
Chemical structure:
pyrazine-2-carboxamide
or pyrazinamide (PZA)

Molecular formula:
C₅H₅N₃O
Sites & mechanism of action:
PZA is a prodrug.
Activated by pyrazinamidase (Pzase)
Susceptible strains release pyrazinamidase which
converts pyrazinamide PZA (prodrug) to active drug
pyrazinoic acid (POA)

POA decreases the pH below that which growth of

Mycobacterium tuberculosis retards and inhibits the
synthesis of fatty acids.
 Firstline agent against Mycobacterium
tuberculosis
 Used in first two month of treatment.
 Used in combination with Rifampicin,
Isoniazid and Ethambutol to treat
tuberculosis .
 Bactericidal in action .
 6-TG or 6-thioguanine
 Thiopurine analogue that is closely related to
mercaptopurine and azathioprine
Pharmacological categories :
Anti metabolite
Anti neoplastic
• Mention in WHO’s essential drug list
• Pregnancy category : D
• Presentation : oral tablet 40mg
• Brands : Tabloid , Lanvis
• Pale yellow , odorless crystalline powder
• Insoluble in water , alcohol, chloroform
• Readily soluble in dilute aqueous alkali
Molecular formula :
C₅H₅N₅O

2-amino-6-thiol
OR
2-amino-6-mercaptopurine
 Thioguanine competes with hypoxanthine and guanine,
for the enzyme hypoxanthine guanine phosphoribosyl
transferase (HGPRTase).
 Then it converts itself into 6-thioguanilyic acid
(TGMP).
 TGMP reaches high intracellular concentrations at
therapeutic doses.
 TGMP interferes with the synthesis of guanine
nucleotides.
 TGMP inhibits purine de novo biosynthesis .
 TGMP inhibits the conversion of inosinic acid
(IMP) to xanthylic acid (XMP)
 Thiogunine nucleotides are incorporated into
DNA,RNA by phosphodiester linkage.
 The overall result of its action is sequential
blockade of the utilization and synthesis of the
purine nucleotides.
Used to treat :
 Acute leukemia
 Acute granulocytic leukemia
 Acute lymphocytic leukemia
 Nephrosis
 Abdominal T.B
 Crohn’s disease