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CYTARABINE Synthesis, SAR, MCQ,Structure,Chemical Properties and Therapeutic Uses

CYTARABINE Synthesis, SAR, MCQ,Structure,Chemical Properties and Therapeutic Uses




Cytarabine

 IUPAC nomenclature

4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5- (hydroxymethyl)oxolan-2-yl] pyrimidin-2-one

Classification

Cytarabine falls under the category of pyrimidine antagonist antimetabolite.

Physiochemical Properties

S. NO. PHYSICAL AND CHEMICAL PROPERTIES
1 Molecular weight 243.22 g/mol
2 Appearance Colorless crystalline powder
3 Melting point 212.5 °C
4 Solubility It is freely soluble in water
5 Octanol water partition coefficient -2.8
6 Presence of ring Pyrimidine and a Tetrahydrofuran ring.

Mechanism of Action

i. Cytarabine gets converted into active form cytarabine triphosphate by the action of deoxycytidine kinase within the cell.

ii. Competition of cytarabine triphosphate for the DNA polymerase enzyme inhibits the synthesis of DNA.

iii. Further, the drug produces cytotoxicity in the cell through incorporation into DNA and RNA.

iv. Cytarabine produces its effects mainly on the cell which are actively dividing by blocking the progression of the cell from G-1 phase to the S phase.

v. These overall results in the death of the actively dividing cells. [1]

Structural Activity Relationship

  • The molar refractivity of the Y substituent will produce increase in the activity of drug.
  • Substituent at Y with (CH2)3NRiR2 with R2 = COCH3, COC6H5, or COOCeH5 will produce a negative effect on the activity of the drug.
  • SH at 4th position will increase the activity of drug.
  • Substituent which are bulky in nature at Y position will produce negative effect on activity due to steric hindrances.
  • Electron withdrawing groups at 5th position will increase the activity of drug. [2]

Methods of Synthesis                                                                       

i. Cytidine and fuming nitric acid are reacted to form cytidine 2’,3’,5’-trinitrate.

ii. 2’,3’,5’-trinitrate is boiled in alcohol containing dilute NaOH which results in the formation of inverted 2’-hydroxy compound.

iii. The compound undergoes saponification for the removal of extra nitrate groups.

 

Therapeutic Uses

  • Acute myelogenous leukemia
  • Chronic mylogenous leukemia
  • Acute lymphocytic leukemia
  • Acute promyelocytic leukemia
  • Hodgkin’s lymphoma
  • Meningeal leukemia
  • Cancers found in the lining of brain and spinal cord

Side Effects/Adverse event

  • Common side effects includes diarrhea, nausea, vomiting, headache, mouth sores and low blood counts.
  • Some other side effects which the patient may experience includes Diarrhea, Loss of appetite, Skin rashes, Hair thinning or hair loss, Eye pain, Flu-like symptoms, Dizziness, etc.

MCQs

Q.1 Which term is NOT associated with the drug Cytarabine?

a) 4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5- (hydroxymethyl)oxolan-2-yl] pyrimidin-2-one

b) Cytosar-U

c) Alkeran

d) Cytabin

Q.2 Match the following with respect to the physical forms of drugs

i.  Azathiprine A. Colorless crystalline powder
ii. Chlorambucil B. White crystalline powder
iii. 5-FU C. White granular powder
iv. Cytarabine D. Pale yellow crystalline powder

 a) i-A, ii-B, iii-D, iv-C

b) i-B, ii-C, iii-A, iv-D

c) i-A, ii-B, iii-C, iv-D

d) i-D, ii-C, iii-B, iv-A

Q.3 The drug Cytarabine shows its action through

a) Producing osmotic imbalance in the cell

b) Competition for DNA polymerase enzyme

c) Leading the cell to the G0 phase

d) Membrane proliferation of the cell

Q.4 The correct order for the synthesis of the drug Cytarabine can be?

I. Boiling with alcohol in presence of alkali hydroxide

II. Reaction of Cytidine with Fuming Nitric acid

III. Boiling with alcohol in presence of Haloacids

IV. Saponification

a) II – I – IV

b) II – III – I – IV

c) II – III – IV

d) II – IV – III

Q.5 Predict the INCORRECT statements from the following with respect to the classification of the drug.

I. Chlorambucil can be classified as an alkylating agent.

II. Cytarabine falls under the category of purine antagonist antimetabolite.

III. Azathioprine falls under the category of purine antagonist antimetabolite.

IV. Fludarabine falls under the category of pyrimidine antagonist antimetabolite

a) I & III

b) II & IV

c) II & III

d) I & II

Q.6 The correct sequence of True and False for the given statements with respect to the side effects of drug Cytarabine is

I. Headache

II. Low blood counts

III. Eye pain

IV. Loss or thinning of hair

a) TTTF

b) TFTF

c) FTFT

d) TTTT

 

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

a) 5-Flourouracil

b) Clorambucil

c) Cytarabine

d) Mechlorethanamine

ANSWERS

1-c

2-d

3-b

4-a

5-b

6-d

7-c

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REFERENCES

[1] KREMER WB. Drugs five years later: cytarabine. Annals of internal medicine. 1975 May 1;82(5):684-8..

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




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