[Screening of antineoplastic antibiotics using a rapid method of evaluating their cytostatic effect on tumor cells]. / Otbor protivoopukholevykh antibiotikov s ispol'zovaniem ekspress-metoda otsenki ikh tsitostaticheskogo deistviia na opukholevye kletki.

The study was aimed at development of a rapid method for estimating in vitro cytostatic action of antitumor antibiotics on the basis of intensity of inclusion of labeled precursors into nucleic acids of tumor cells which should be useful in primary screening of antibiotics with potential antitumor activity. The method was applied to substances isolated from 600 cultures of actinomycetes. 35 antibiotics showed antitumor activity; 8 of them were studied in detail. They proved to be novel antibiotics having antitumor activity in animals.

[The antineoplastic antibiotic polypeptide 308 produced by Actinomadura recticatena. Its isolation and physicochemical properties]. / Protivoopukholevyi antibiotik-polipeptid 308, produtsiruemyi Actinomadura recticatena. Vydelenie i fiziko-khimicheskie svoistva.

A antitumor antibiotic belonging to the group of polypeptide antibiotics containing chromophore was isolated from the culture of Actinomadura recticatena Terekhova, Preobrazhenskaya et Galatenko, 1984, strain 308. Biosynthesis, isolation, physicochemical and biological properties of the antibiotic are described. The results of elemental analysis, the melting point, optical properties, UV, IR and NMR spectra and the data on acid hydrolysis showed that antibiotic 308 was most closely related to antibiotic BBM-928 A.

[Cytostatic action of N-ethyl-13-dihydrorubomycin on the cells of various tumor strains]. / Tsitostaticheskoe deistvie N-étil-13-digidrorubomitsina na kletki nekotrykh shtammov opukholei.

The cytostatic effect of rubomycin and N-ethyl-13-dihydrorubomycin, its semisynthetic derivative, was studied with a radiometric method based on measuring the intensity of labeled thymidine incorporation into the tumor cells of NK/Ly, sarcoma 37 and leukemia P-388 and a method for total determination of nucleic acids in the cell hydrolysates of these tumor strains. Spectrophotometric determination of the total content of DNA and RNA in the tumor cells of NK/Ly showed that the inhibitory effect of the derivative was 6 times higher than that of rubomycin. Radiometric estimation of their cytostatic activity and the studies with the cells of ascitic sarcoma 37 and leukemia P-388 demonstrated that the inhibitory effect of N-ethyl-13-dihydrorubomycin was lower than that of rubomycin.

[Use of an express method in studying the cytotoxic action of antitumor antibiotics]. / Ispol'zovanie ékspress-metoda pri izuchenii tsitotoksicheskogo deistviia nekotorykh protivoopukholevykh antibiotikov.

The cytostatic effect of some antitumor antibiotics such as carminomycin, olivomycin, bruneomycin, rubomycin C and adriamycin was studied with a rapid method based on measurement of 3H-thymidine and 14C-adenine incorporation into the tumor cells of suspended primary cultures of mouse lymphadenosis NK/Ly. The method is recommended for screening of antitumor antibiotics.

[Cytostatic action of semisynthetic rubomycin derivatives]. / Izuchenie tsitostaticheskogo deistviia nekotorykh polusinteti-cheskikh proizvodnykh rubomitsina.

The cytostatic effect of some semi-synthetic derivative of rubomycin, an antitumor antibiotic, was studied with two methods, i.e. the method of spectrophotometric determination of the increase of the total amount of nucleic acids and the radiometric method based on measuring the intensity of incorporation of labeled thymidine. The results obtained with the two methods were similar. 9 semi-synthetic derivatives of rubomycin were studied with respect to the tumor cells NK/Li. The cytostatic effect of 8 out of these derivatives was 2-170 times lowers than that of rubomycin. The cytostatic effect of N-ethylrubomycin was equal to that of the initial antibiotic.

[Cytostatic action of semisynthetic derivatives of carminomycin]. / Izuchenie tsitostaticheskogo deistviia nekotorykh polusinteticheskikh proizvodnykh karminomitsina.

The cytostatic effect of some semi-synthetic derivatives of carminomycin on the tumor cells of mouse lymphadenosis (NK/Ly was studied in primary suspended cultures. A rapid method developed by the authors was used for determination of the drug cytostatic effect. The method is based on measuring the intensity of 3H-thimidine incorporation into the tumor cells. Simultaneously a method based on estimation of the increase of the total amount of the nucleic acids was used. No derivative superior to the initial drug by the level of the cytostatic effect on the tumor cells was found.

[Intensification of the cytostatic action of adriamycin and carminomycin by amphotericin B]. / Ob usilenii tsistostaticheskogo deistviia adriamitsina i karminomitsina amfoteritsinom B.

Amphotericin B has a significant cytostatic effect on lymphadenosis cells of mice NK/LY. In a concentration of 6 units/ml it inhibits an increase in total nucleic acids by 50 per cent. Such cytostatic effect of amphotericin B combines with the effect of carminomycin and adriamycin. In concentrations having no cytostatic effect amphotericin B does not enhance the action of adriamycin and carminomycin on tumor cells.

[Synthesis and antitumor action of 14-N-substituted derivatives of rubomycin and karminomycin]. / Sintez i protivoopukholevoe deistvie nekotorykh 14-N-zameshchennykh proizvodnykh rubomitsina i karminomitsina.

The reaction of nucleophilic substitution of 14-bromine derivatives of carminomycin and rubomycin with respective nitrogen-containing heterocycles yielded six novel derivatives of carminomycin and rubomycin: 14-N-imidazolyl-carminomycin, 14-carminomycyl-N-pyridinium bromide, 14-carminomycyl-N-(3-aminocarbonyl)-pyridinium chloride, 14-rubomycyl-N-(3-amino-carbonyl)-pyridinium chloride, 14-N-succinimidocarminomycin and 14-N-succinimidorubomycin. In vitro and in vivo antitumor activity of the above derivatives and three other derivatives described earlier: 14-rubomycyl-N-pyridinium bromide, 14-N-imidazolylrubomycin and 14-N-phthalimidorubomycin was studied. It was shown that in vitro all the 9 semisynthetic derivatives had a lower (by 1.5-6 times) cytostatic action on murine lymphadenosis cells NK/LI as compared to the initial antibiotics. The in vivo experiments on mice revealed that by acute toxicity the rubomycin derivatives administered intravenously were close to rubomycin, whereas the toxicity of the analogous derivatives of carminomycin was 5-17 times lower. The in vivo experiments also showed that seven out of the nine 14-N-substituted derivatives of carminomycin and rubomycin were practically deprived of antitumor activity (strain LIO-1), while 14-carminomycyl-N-pyridinium bromide and 14-N-succinimidocarminomycin inhibited the tumor growth by 40-60 per cent.