6 – Thioguanine

• 6 thioguanine comes under the category of Purine
antagonist antimetabolite.

• It is thio analogue of naturally occurring purine base
guanine.

Structure of 6 – Thioguanine: 

IUPAC name: 2-
amino-3,7 dihydro  purine -6 – thione

Mechanism
of Action of 6 – Thioguanine

• 6-Thioguanine interacts with enzyme hypoxanthine-guanine
phosphoribosyl transferase(HGPRTase) and gets converted into 6-thioguanosine
monophosphate(TGMP).

• 6-thioguanosine monophosphate (TGMP) accumulates in the
cells and inhibits the conversion of inosinic acid to xanthylic acid. This
leads to the inhibition of synthesis of guanine nucleotide.

• TGMP is converted by phosphorylation to thioguanosine
diphosphate (TGDP) and thioguanosine triphosphate (TGTP).

• The TGMP, TGDP and TGTP are collectively named
6-thioguanine nucleotides (6-TGN).

• 6-TGN are cytotoxic to cells by: (1) incorporation into
DNA during the synthesis phase (S-phase) of the cell.

• Thus, the effect of this drugs against the tumor cell may
be due to the both actions

1. Inhibition of purine synthesis

2. As well as through induction of cytotoxicity in the
cell. 

Therapeutic
uses of 6 – Thioguanine:

• 6 -Thioguanine is given for the treatment of acute
myelogenous leukemia (a type of cancer that begins in the white blood cells)

• It can be also used for the treatments of chronic
myelogenous leukemia.