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6-THIOGUANINE Synthesis, SAR, MCQ,Chemical Structure and Therapeutic Uses

6-THIOGUANINE Synthesis, SAR, MCQ,Chemical Structure and Therapeutic Uses




6-Thioguanine (6-TG) 

 

IUPAC nomenclature

2-amino-1H-purine-6(7H)-thione

 

Classification

6-Thioguanine falls under the category of purine antagonist antimetabolite.

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 167.19g/mol
2 Appearance Yellow crystalline powder
3 Melting point More than 360 °C
4 Solubility Insoluble in water. Soluble in alkali hydroxides.
5 Octanol water partition coefficient -0.07
6 Presence of ring Purine ring system

 

Mechanism of Action

i. 6-Thioguanine interacts with enzyme hypoxanthine-guanine phosphoribosyltransferase and gets converted into 6-thioguanosine monophosphate.

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

iv. Further, thioguanine nucleotides get inserted in the DNA as well as in the RNA of cells and he false sequencing of these results in the cytotoxicity of the cell.

v. Thus, the effect of this drugs against the tumor cell may be due to the both actions, inhibtition of purine synthesis as well as through induction of cytotoxicity in the cell. [1]

Structural Activity Relationship

  • The activity of the drug increases with increase in the carbon chain upto 15-16 carbons, after that, it again decreases.
  • Substituent at position 6 which can lead to the increase in the resonance at 6th position will lead to increase in the activity of the drug.
  • Introduction of the hydrophobic substituent at 6th position will increase the activity of the drug.
  • Substitutions at 2nd position may not change the activity of the drug, or it may decrease the activity of the drug depending upon the type of substituent. [2]

Methods of Synthesis

6-Thioguanine can be synthesised through thiation of the guanine with phosphorous pentasulfide.

 

Therapeutic Uses

  • This drug is given for the treatment of acute myelogenous leukemia
  • It can be also used for the treatments of chronic myelogenous leukemia but in this case, it is not the first choice.

Side Effects

  • Low bloodcounts and liver toxicity are common side effects of this drug.
  • Other side effects can be nausea, loss of appetites, infertility and some liver problems.
  • Some of the uncommon side effects includes tumor lysis syndrome and vino-occlusive liver disease

MCQs

Q.1 ‘2-amino-1H-purine-6(7H)-thione’ is the IUPAC nomenclature of which drug?

a) Dacarbazine

b) Etoposide

c) Vinblastine

d) 6-Thioguanine

Q.2 Predict the incorrect statement related to the therapeutic uses of drug 6-Thioguanine.

a) 6-thioguanine guanine can be used for the treatment of acute myelogenous leukemia

b) 6-thioguanine guanine can be used for the treatment of chronic myelogenous leukemia

c) It is also used for the cure of diabetes mellitus

d) It is an anticancer drug

Q.3 Match the following with respect to the SAR of drug 6-Thioguanine

i. Increase in the carbon chain length A. Increase the activity of drug
ii. Introduction of the hydrophobic substituent on 6th position                                               B. increase the activity of drug
iii. Introduction of substituent on 2nd position C. Decrease the activity of drug
iv. Introduction of substituent at 6th position which increases resonance D. Increase the activity of drug

a) i-d, ii-c, iii-b, iv-a

b) i-a, ii-b, iii-c, iv-d

c)i-c, ii-b, iii-a, iv)

d) i-b, ii-a, iii-d, iv-c

Q.4 Which amongst the following drugs shows its effect through inhibition of purine synthesis in the cell?

a) 6-TG

b) 5-FU

c) DTIC

d) BCNU

Q.5 6-TG drug belongs to which class?

a) Pyrimidine antagonist antimetabolites

b) Purine antagonist antimetabolites

c) 5-alpha reductase inhibitors

d) Progestins

Q.6 Which of the following is not a side effect of 6-Thioguanine

a) Myelogenous leukemia

b) Liver disorders

c) Low blood counts

d) Nausea

 Q.7 Which amongst the following drugs is having least number of ring system in its structure-

a) Methotrexate

b) Morphine

c) Penicilline g

d) 6-Thioguanine

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ANSWERS

1-d

2-c

3-b

4-a

5-b

6-a

7-d

 

REFERENCES

[1] Nelson JA, Carpenter JW, Rose LM, Adamson DJ. Mechanisms of action of 6-thioguanine, 6-mercaptopurine, and 8-azaguanine. Cancer Research. 1975 Oct 1;35(10):2872-8.

[2] Gupta SP. Quantitative structure-activity relationship studies on anticancer drugs. Chemical reviews. 1994 Sep;94(6):1507-51.




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