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]]>2-Amino-N,N′- bis[(6S,9R,10S,13R,18aS)-6,13-diisopropyl-2,5,9-trimethyl-1,4,7,11,14-pentaoxohexadecahydro-1H-pyrrolo[2,1-i][1,4,7,10,13]oxatetraazacyclohexadecin-10-yl]-4,6-dimethyl-3-oxo-3H-phenoxazine-1,9-dicarboxamide.
Actinomycin D falls under the category of Antibiotic cytotoxic drug. [1]
S. NO. | PHYSICAL AND CHEMICAL PROPERTIES | |
1 | Molecular weight | 1255.4g/mol |
2 | Appearance | Bright red rhomboid prisms / red powder |
3 | Melting point | Range between 245-248°C |
4 | Solubility | 1 gm can be dissolved in 1000 ml of water |
5 | Octanol water partition coefficient | 3.21 |
6 | Presence of ring | Phenoxazone ring structure |
i. Dactinomycin binds with DNA.
ii. RNA synthesis is prevented.
iii. Thus, protein synthesis will be disturbed. [2]
i. Dactinomycn is synthesized during the culture of Streptomyces antibioticus.
ii. It is purified with the help of chromatographic and crystallization methods.
TOTAL SYNTHESIS METHOD
i. Mixed anhydride frombenzyl-oxocarbonyl-L-N-methylvaline and isobutylchloroformate were treated with t-butyloxycarbonyl-L-threonine.
ii. Countercurrent distribution of the formed compound gave O-(benzyloxycarbonyl-L-N-methylvalyl)-N-t-butyloxycarbonyl-L-threonine.
iii. The catalytic hydrogenation of the above compound gave O- (L-N-methylvalyl)-N-t-butyloxycarbonyl-L-threonine.
iv. Condensation of the above compound with benzyloxycarbonylsarcosine with mixed carboxylic-carbonic anhydride method gave O- (benzyloxycarbonylsarcosy1-L-N-methylvaly1)-N-t-butyloxycarbonyl-L-threonine.
v. Condensation of the above formed compound with t-butyl D-valyl-L-prolinate by mixed anhydride method gave O-(benzyloxycarbonylsarcosyl-L- N – methylvalyl) – N – t- butyloxycarbonyl-L-threonyl-D-valyl-L-proline t-butyl ester.
vi. It was purified with counter current distribution method.
vii. The above formed compound was then treated with 0.4M solution of boron trifloride in glacial acetic acid to give chromatographically uniform yield.
viii. The crude product was purified using column chromatographic technique after treating the product with 2-nitro-3-benzyloxy-4-methylbenzoyl chloride.
ix. Product was then treated with di-p-nitrophenyl sulfite in pyridine to give nitrophenyl ester.
x. Benzoylcarbonyl group was removed by treatment with -5 N hydrogen bromide in dioxane.
xi. Purification of the product through column chromatography on Sephadex LH-20 in methanol will give cyclic pentapeptide lactone derivative.
xii. Catalytic hydrogenation followed by oxidation with potassium ferricyanite in methanol-phosphate buffer will give actinomycin D. [4]
Dactinomycin is used for the treatment of :
Q.1 The term ‘DACMOZEN’ is associated with which drug?
a) Dactinomycin
b) Mitomycin
c) Bleomycin
d) Mitoxantron
Q.2 Predict the incorrect statement related to the therapeutic uses of drug Actinomycin D-
a) It is used for Wilms’ tumor
b) It is used for Hodgkin’s myloma
c) It is used for Osteosarcoma
d) It is used for Ewing’s sarcoma
Q.3 Match the following with respect to the SAR of drug Dactinomycin-
i. Lactone ring | A. Biological activity of group |
ii. Hydroxyproline group | B. Stabilizes the conformation of drug |
iii. Peptide groups | C. Changes in the minimal inhibitory concentration of drug |
iv. Pipecolic acid introduction | D. Decrease in the activity of drug |
a) i-C, ii-D, iii-B, iv-A
b) i-D, ii-B, iii-C, iv-A
c) i-B, ii-C, iii-A, iv-D
d) i-A, ii-B, iii-D, iv-C
Q.4 Which amongst the following drugs shows its effect through Binding with DNA and inhibition of RNA synthesis?
a) Cyclophosphamide
b) Methotrexate
c) Cytarabine
d) Dactinomycin
Q.5 Dactinomycin drug belongs to which class?
a) Progestins
b) Folate Antagonist
c) Antibiotics
d) Nitrogen mustards
Q.6 Which of the following is not a side effect of Actinomycin D?
a) Hair loss
b) Weight gain
c) Loss of appetite
d) Skin problems
Q.7 Phenoxazone ring structure is present in which drug?
a) Actinomycin D
b) Carmustine
c) Dacarbazine
d) None of the above
1-a
2-b
3-c
4-d
5-c
6-b
7-a
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