ACTINOMYCINUMS — group of the antibiotics produced by various strains of the actinomycetes having similar chemical constitution and physical properties.
And. — chromoproteids in which a peptide part is connected with quinoid chromophoric group. Separate And. differ from each other in quantitative and qualitative composition of amino acids in a peptide part whereas chromophoric group (3-амино-2-кето-1,8-диметилфенокса-зин-4,6-дикарбоновая to - that) at all And. it is identical.
And. — crystal substance of red color. Well than a rastvorima in chloroform, acetone, it is worse — in methanol, ethanol, benzene, ether and water. Solubility of Actinomycinum With in water and isotonic solution of sodium chloride makes respectively 200 and 250 mkg/ml. In aqueous solutions And. are inactivated at a deviation from neutral reaction of the environment. During sterilization at high temperature there is also a decomposition And.
And., formed by strains producers, represent mixes of non-constant structure: a ratio of the making versions And. substantially depends on conditions of fermentation, to-ruyu carry out by a deep method on the Wednesdays containing starch, peptone, corn extract, soy flour and other components. Drugs A. receive by extraction by organic solvents with the subsequent recrystallization and hromatografichesky cleaning.
And. possess strong action on gram-positive bacteria and some fungi. Action is more weakly expressed And. on gram-negative bacteria. Action And. consists in suppression of synthesis of RNA (transcription) on a DNA matrix. Such effect is explained by linkng of molecules of an antibiotic with the guaninovy remains of DNA. Experiences in acellular system showed that the DNA-dependent RNA polymerase has low activity during the use as a matrix of a complex between DNA and And. At the same time And. DNA replications in the doses sufficient for suppression of synthesis of RNA do not interfere. Thanks to it in the cells processed And., synthesis of RNA and protein whereas synthesis of DNA continues selectively is suppressed.
Use And. as selective inhibitor of synthesis of RNA played a big role in researches on interpretation of molecular mechanisms of genetic processes. There are messages on suppression And. biosynthesis of purines. This effect, however, is collateral and cannot be the cause of antibiotic action
of A. A. do not exert impact on synthesis of RNA on RNA matrixes and therefore do not affect directly reproduction of RNA-containing of viruses. As a result of the mutations changing permeability of a cover of cells to And., there are bacterial strains steady against
A. A. possess antineoplastic action, and also promote suppression of reaction of rejection of the transplanted fabrics thanks to the expressed immunodepressive properties.
Antineoplastic Actinomycinums. In oncological practice use four drugs: hrizomallin, aurantin, aktipomitsin D and S.'s
Hrizomallin Actinomycinum (Chrysomal-linum) is produced by a fungus of Actinomyces chrysomallus (across Krasilnikov) or Streptomyces chrysomallus (across Vaksman). Crystal powder of yellow-orange color, we will badly dissolve in water, it is easy — in alcohol. Possesses a wide range of antineoplastic action. Apply at a choriocarcinoma (horionepitelioma) of a uterus, a small egg, Vilms's tumor at children. At a horionepitelioma of a uterus appoint as independently, and in combination with a methotrexate, Mercaptopurinum and radiation therapy. Hrizomallin is effective also at ovarian cancer and a lymphogranulomatosis, but acts more weakly, than other known antineoplastic drugs. Feature of a hrizomallpn (and to a certain extent and an aurantina) is very weak influence on a hemopoiesis. Hrizomallin enter intravenously (slowly). Before introduction dissolve spirit of a hrizomallin in 5 — 10 ml of isotonic solution of sodium chloride. The adult enter since 0,5 mg, at good tolerance increase a dose to 0,75 — 1 mg. The drug is administered every other day or 1 time in 3 days. The general dose on a course of treatment of 7 — 10 mg. With effect and good tolerance the course is repeated in 4 — 6 weeks. The drug is administered to children at the rate of 0,015 — 0,02 mg on 1 kg of body weight. If in cavities there are exudates, make also intracavitary introduction of a hrnzomallin (in belly and pleural cavities). The drug is not administered under skin and intramusculary since possibly formation of infiltrates. At treatment hrizomalliny the loss of appetite, nausea, vomiting, a hair loss, oppression of a hemopoiesis is sometimes observed. At persistent nausea and vomiting appoint aminazine, piridoksinony emergence of diarrhea and stomatitis is possible; in these cases treatment is temporarily stopped. In the course of treatment it is necessary at least 1 time a week to investigate blood (control of the maintenance of leukocytes and thrombocytes) and I wet on protein. Drug is contraindicated at a cachexia, in end-stages of malignant process, at falloff of hemoglobin, leukocytes and thrombocytes. Hrizomallin is issued in ampoules on 0,5 mg of the drug dissolved in 45% alcohol. Storage according to the list A in the place protected from light at a temperature not over 5 °.
Aurantinum is produced by a fungus of Actinomyces aurantiacus (across Krasilnikov) or Streptomyces aurantiacus (across Vaksman). Drug is used at a lymphogranulomatosis, cancer of a rectum, some forms hron. lympho-both myeloleukemia and retikulolimfosarkomatoza. Aurantinum is entered intravenously adult in a single dose of 500 — 1000 mkg with an interval of 2 — 4 days (depending on portability); the general dose — 5000 — 10000 mkg. The single dose for children makes 8 — 10 mkg on 1 kg of weight.
Actinomycinum of D (Actinomycinum D; the synonym Dactinomycinum) is produced by a fungus of Actinomyces parvullus (across Krasilnikov) or Streptomyces parvullus (across Vaksman). It is applied in a combination with radiation therapy at treatment of children with Vilms's tumor to prevention of a postoperative recurrence and metastasises, and also in case of nonresectable tumors. It is shown also at a rhabdomyosarcoma and a neuroblastoma at children. At a choriocarcinoma (horionepitelioma) treatment by Actinomycinum of D causes remissions in 50% of cases in women. The drug is administered intravenously on 10 — 15 mkg on 1 kg of body weight of the patient, daily or every other day; the general dose from 50 to 75 mkg on 1 kg of body weight. The course of treatment is repeated in 4 weeks. Children are allowed to enter in 8 — 10 days a total dose of 80 — 100 mkg on 1 kg of body weight.
Actinomycinum With was not widely adopted in clinical practice, however it was effective at treatment of a lymphogranulomatosis, in particular at early stages, and also at Brill's disease — Simmersa and hron. lymphoid leukosis. A dosage — 200 — 400 mkg intravenously every other day or daily. The general dose on a course of treatment — to 10000 mkg.
Bibliography: Herald M. Antibiotics, the lane from Czeches., M., 1966; Ermolyeva Z. V. Antibiotics, interferon, bacterial polysaccharides, M., 1968, bibliogr.; Kozhybski T., Kovshyk-Gindifer Z. and Kurylovich Century. Antibiotics, the lane with polsk., t. 1 — 2, Warsaw, 1969; The Mechanism of action of antibiotics, the lane with English, under the editorship of G. F. Gauz, M., 1969; Sazykin Yu. O. Antibiotics as inhibitors of biochemical processes, M., 1968; Shemyakin M. M. and d river. Chemistry of antibiotics, t. 1 — 2, M., 1961.
Antineoplastic And. — Astrakhan V. I. and Garin A. M. Clinical use of antineoplastic antibiotics Antibiotics, t. 12, No. 2, page 167, 1967, bibliogr.; Aurantin — antineoplastic antibiotic drug from group of Actinomycinums, under the editorship of X. X. Planelyesa, etc., M., 1962, bibliogr.; Actinomycin, nature, formation and activities, ed. by S. A. Waksman, N. Y., 1968; D'Angio G. J., Farber S. Maddock of S. of L. Potentiation of X-ray effects by actinomycin D, Radiology, v. 73, p. 175, 1959.
V. R. Sobolev; V. I. Astrakhan (PMC.)