ACTINOMYCINS

Actinomycins are the antibiotics first isolated from a culture of Streptomyces antibioticus by Waksman and Tishler in 1942. Now many naturally occurring actinomycins have been isolated from various genera of the actinomycetes. Actinomycins possess potent antitumor and cytotoxic effects and show bacteriostatic activity against gram-positive bacteria.

The actinomycins are yellow or red peptide-containing derivatives of phenoxazine. The chromophore of the molecule is 2-amino-4,6-dimethyl-3-oxophenoxazine-1, 9-dicarboxylic acid.

Actinomycin C is a mixture of actinomycin D. (10%), actinomycin C (45%)andactinomycin C (45%). In actinomycin C series, the only variations that occur are in the two D-valine components. Actinomycin C, contains two D-alloisoleucine components in place of the two D-valine components. The structure of actinomycin C contains one D-valine component and one D-alloisoleucine component. Changes in other subgroups give other series of actinomycines. For example, in the actinomycin X series, changes in the L-proline component occur. In the actinomycin E series, changes in the L-N-methylvaline component occur. In the actinomycin F series, additional sarcosine components are present in subgroup 3 substituted for proline components.

In addition to the naturally occurringamino acids found iň Cseries, other amino acids may be present into the actinomycin molecule. Some actinomycins have been prepared by synthetic methods.

The cytotoxic effect of actinomycins is due to an inhibition of protein synthesis. They bind reversibly to the guanidine moiety of DNA.

Actinomycin F 1(Brand Names : Actinomycin KS4; KS4) is an antibiotic produced by cultures of actinomycin C-elaborating strains of Streptomyces. It is considered to be a derivative of actinomycin C. Amino acid analysis indicates that the prolines present in actinomycin C, are substituted by sarcosine in actinomycin F. It is used as antineoplastic agent.

 Dectinomycin (Brand Names: Actinomycin D; Meractinomycin; Actinomycin Ay; Actinomycin IV/C/I,/ X: NSC3053; Cosmegen)  Dactinomycin is an antibiotic substance belonging to the actinomycin complex and produced by several Streptomyces species such as S. Chrysomalus and S. antibioticus. The component amino acids in the cyclic peptides attached to carbon atom 1 and to carbon atom 9 are identical in nature and arrangement.

Dactinomycin is a bright, red, somewhat hygroscopic crystalline powder, m.p. 241-243 (decomp). It is soluble in water; freely soluble in alcohol; very slightly soluble in ether. It is stored at a temperature not exceeding 40° in air-tight containers and protected from light. Dilute solutions are very sensitive to light. –

Uses: Dactinomycin is a highly toxic antibiotic with antineoplastic and immunosuppressant properties. It inhibits the proliferation of cells by forming a stable complex. It is used in the treatment of Wilms' tumour, rhabdomyosarcoma, tumors of the uterus and testis, in Ewing's sarcoma, osteogenic sarcoma, Kaposi's sarcoma and other solid tumors.

Adverse Effect

Adverse effects include toxicity, anorexia, nausea, vomiting, allergic reactions and local irritant effects, bone-marrow depression, anaemia and bleeding.