| Name: |
Actinomycin D |
|---|
| Generic Names: |
Actinomycin C1[1],[2]
NSC-3053[3]
Dactinomycin[2]
|
| Trade Names: |
Cosmegen®,Merck[2]
|
| IUPAC name: |
|
| Molecular Weight: |
1255.45 daltons[2] |
|---|
| Structure: |
 [4],[5],[6],[1],[7],[8],[9],[10],[11]
Molecule consists of an approximately planar phenoxazone ring system connected by amide linkages to two identical cyclic pentapeptide lactones[2]
The outer face of the drug is mainly hydrophobic,
with a few carbonyl oxygen atoms coming out. This characteristic is
necessary for transporting the molecule through membranes before it
actually reaches its target.[2]
Drug exhibited conformational flexibility controlled by localized hinge regions[2]
|
| Functional Group/chemical constitution: |
Lactone groupimgs, D-valyl groups[12]
two cyclic pentapeptide
linkages [7], termed as alpha-ring and beta-ring, attached to the quinonoid and benzenoid rings of the phenoxazone
group[4]
phenoxazone chromophore of the drug has amino-substituted quinonoid end and the benzenoid end [2]
|
| Chemical Nature: |
Lipid-soluble, uncharged[13]
Actinomycin D is soluble in alcohols, but only
sparingly soluble in water.[2]
Actinomycin shows a remarkable increase in solubility
with temperature decrease[14]
|
| Actions & Indications: |
Pharmcological Action-
Anti-timor activity[15], [16]
Bacteriostatic activity especially against gram-positive bacteria[17]
cytotoxic antibiotic[18], [16]
Preclinical study-
Actinomycin D alone proved effective in children with rhabdomyosarcoma, Wilm’s tumor, sarcoma of mesentry[19]
Actinomycin D at, 0.1 µg/ml
inhibits production of mouse leukemia virus(MLV) by JLS V-5
cells in tissue culture.[20]
|
Notes: |
Actinomycin D activity is dependent on ability of cells to accumulate and retain the drug, as evidenced by study with mouse leukemia in vitro[13]
Treatment of amphibian embryonic cell with Actinomycin D, led to appearance of chromosomal threads in area of nucleus which are otherwise empty[21]
actinomycin D(IP injection) from same lot has been shown to exhibit unexplainable variation in its antitumor effect in mouse tumors [22]
It was shown that under anaerobic conditions the
ferredoxin reductase/NADPH system could reduce actinomycin D to produce a semiquinone-imine free radical; however intercalated actinomycin D did not undergo reduction by this system. Under aerobic conditions the ferredoxin reductase/NADPH/actinomycin D system generated the superoxide anion radical[23]
To minimize cell-to-and dish-to-cell
Interactions and toxicity of the drug, adequate rinsing,
minimal cell inocula, and large final volumes of
growth medium should be used[24]
|
| Actinomycin Dresistance: |
Resistant cells:
HeLa-R-4 cells[25]
Sensitive cells:
HeLa-S cell[25]
Cells in G2(G-mitosis) phase are found to be resistant to action of actinomycin D in an in vitro study with Chinese hamster ovary cells[26],[24]
Chinese hamster ovary cells become resistant to actinomycin D in the latter part of S phase. [25]
G1 phase was found to be sensitive to the action of actinomycin D in a study with mice crypt cells in vivo[27]
|
| REFERENCES |
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