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Biomedical subjects

E N Olsuf'eva

Publications and source records attributed to E N Olsuf'eva.

At least 19 recordsLinked to original sources
PubMed2000

[Study of dimerization of polysynthetic derivatives of the antibiotic eremomycin by ESI MS and its role in elucidating antibacterial activity].

The dimerization constants for glycopeptide antibiotics vancomycin, ristocetin, and eremomycin and nine semisynthetic eremomycin derivatives were determined by the electrospray ionization mass spectrometry; the constants for natural antibiotics turned out to be close to those previously determined by NMR. No correlation between these dimerization constants and antibacterial activities of all the compounds toward the clinical strains of Gram-positive bacteria was found.

Anti-Bacterial Agents↗
PubMed1997

[Non-natural aglycones of glycopeptide antibiotics of the vancomycin group. Synthesis and antibacterial activity].

A new approach for the modification of the heptapeptide core of glycopeptide antibiotics was proposed based on the replacement of amino acid residues in positions 1 and 3 in teicoplanin aglycone and in position 1 in the eremomycin aglycone. Six novel nonnatural aglycones of the vancomycin type were obtained. Compounds derived from the teicoplanin aglycone exhibited in vitro activity against Gram-positive bacteria, and two of them were also active against the vancomycin-resistant enterococci.

Anti-Bacterial Agents↗
PubMed1997

[Glycopeptide antibiotics resistance mechanism as the basis for novel derivatives development capable to overcome resistance].

The data on the genetic and biochemical bases of bacterial resistance to antibiotics of the vancomycin-ristocetin group are summarized. Special emphasis is placed on the mechanism of resistance associated with target modification and on molecular interactions occurring upon contact of glycopeptides with normal and modified targets. The prospects for developing new derivatives active against resistant bacteria are discussed. The most rational approach to the chemical transformation of glycopeptides involves the modification of the internal "binding pocket" and the peripheral regions of the molecule that participate in the stabilization of the antibiotic-target complex. Novel semisynthetic drugs of this group active against glycopeptide-resistant enterococci are described.

Anti-Bacterial Agents↗
PubMed1995

[14-O-hemiesters and 13-hydrazones of anthracyline antibiotics of the daunorubicin series. Synthesis and cytostatic activity with respect to tumor cells sensitive or resistant to doxorubicin].

Doxorubicin and 14-hydroxycarminomycin 14-O-hemiadipates and 14-O-hemipimelates, synthesized from 14-bromo derivatives of daunorubicin and carminomycin and monosodium adipate and pimelate, were converted to the corresponding N-trifluoroacetylated compounds. 13-(4-Methylpiperazine-1-yl)imino derivatives of the anthracycline antibiotics were also obtained. The cytostatic activity of the compounds synthesized was studied using a panel of human and animal tumor cell lines sensitive or resistant to doxorubicin. N-Trifluoroacetylation of the antibiotics resulted in a decrease in the cytostatic activity. The activity of the water-soluble 13-(4-methylpiperazine-l-yl)imino derivatives is close to that of the corresponding parent antibiotics.

Animals↗
PubMed1991

[Study of the structure of anthracycline antibiotics by ERIAD mass spectrometry].

Fragmentation of antibiotics daunorubicin, carminomycin, doxorubicin and their semisynthetic analogues under conditions of the new mass spectrometry method ERIAD is discussed. Signals of protonated molecular ion (M + H)+ and ions of fragments are present in all the mass spectra. The results are compared with literary data obtained by means of other (EI and FAB MS) mass spectrometry methods.

Antibiotics, Antineoplastic↗
PubMed1991

[The structure and antimicrobial activity of the partial degradation products of the antibiotic eremomycin].

Antimicrobial activity of partial degradation products of eremomycin, a new glycopeptide antibiotic, was studied. The products formed by eremomycin deglycosylation (deseremosaminyl eremomycin, eremosaminyl aglycone and aglycone) and elimination of the chlorine atom from the molecule aglycone moiety (dechloroeremomycin). The spectral data in favour of the compounds structure are presented. It was found that partial degradation led to a decrease in the antimicrobial activity of the antibiotic. Dechloreremomycin had the highest activity among the products. Its MIC for the methicillin-resistant strains of Staphylococcus aureus was only twice as low as that of the initial antibiotic.

Anti-Bacterial Agents↗
PubMed1991

[Synthesis and properties of new rubomycin derivatives].

Condensation of rubomycin (daunorubicin) with respective hydrazides yielded novel substituted hydrazones: 13-cyanoacetyl hydrazone rubomycin, 13-L-phenylalanyl hydrazone rubomycin, 13-BOC-3-(uracilyl-1)-DL-alanyl hydrazone rubomycin and 13-BOC-3-(adenylyl-9)-DL-alanyl hydrazone rubomycin. With successive treatment of rubomycin with hydrazine hydrate and respective ketones novel asymmetric azines were prepared: 13-cyclopentylidene hydrazone rubomycin, 13-alpha,alpha'-dimethyl-cyclopentylidene hydrazone rubomycin and 13-(1-phenylethylidene-1) hydrazone rubomycin. 14-Adenylyl-N9-rubomycin was synthesized by interaction of 14-bromorubomycin with adenine and hydrogenation of its analog, 14-N-imidazolyl rubomycin by sodium borhydrite yielded 13-dihydro-14-N-imidazolyl rubomycin. There was observed correlation between the antimicrobial activity of the derivatives against B. mycoides and their cytostatic effect on the cells of murine leukemia NK/LI. The high in vitro activity of 13-cyclopentylidene hydrazone rubomycin showed satisfactory correlation with the results of the study on the antitumor effect in animals.

Animals↗
PubMed1990

[Study of toxicity and antineoplastic activity of 14-substituted derivatives of rubomycin and carminomycin].

Toxicity and antitumor activity of five derivatives of rubomycin and carminomycin were studied in animals. The derivatives were prepared by modification of the methyl C-14 group. These were the following: 14-chlorrubomycin, 14-chlorcarminomycin, 14-salicyloyloxyrubomycin, 14-salicyloyloxycarminomycin and 14-quinaldinoyloxyrubomycin. The chemotherapeutic study revealed that, in their activity, all the compounds were inferior to the starting antibiotics. Unlike the other derivatives, 14-chlorcarminomycin induced a significant inhibition of leukemia P-388 development (the average lifespan of the mice amounted to 165 per cent as compared to the control). However, in the magnitude of its effect, the derivative was inferior to carminomycin.

Animals↗
PubMed1990

[Synthesis and antitumor activity of new analogs of anthracycline antibiotics modified by aglycon].

Anthracycline antibiotics widely used, along with their semisynthetic analogues, in human cancer chemotherapy, are O-glycosides having as aglycon 7,8,9,10-tetrahydronaphtacenequinone-5,10-with some hydroxy groups, a side chain at C-9 and sugar(s) residues, usually at C-7. The review includes the most important studies on the chemical modification of the aglycon moiety of daunorubicin, doxorubicin and carminomycin during last ten years. Activity of the compounds on experimental tumours is described and their structure-activity relationship is discussed.

Antibiotics, Antineoplastic↗
PubMed1990

[Synthesis and mass-spectrometric analysis of N-cycloalkyl derivatives of carminomycin, daunorubicin and their analogs].

Condensation of carminomycin or daunorubicin with glutaric dialdehyde in the presence of NaBH3CN yielded 3'-deamino-3'-piperidinocarminomycin or 3'-deamino-3'-piperidinodaunorubicin and corresponding (13-R, S)-dihydroderivatives. To prepare similar derivatives of 14-hydroxycarminomycin or doxorubicin, 13-dimethylketals of 14-bromocarminomycin or 13-bromodaunorubicin were used in the reaction of reductive alkylation with glutaric or glycolic dialdehyde to give 3'-deamino-3'-piperidino- or 3'-deamino-3'-morpholino derivatives of 13-dimethylketals of 14-bromocarminomycin or daunorubicin, respectively. After deblocking and subsequent hydrolysis of these compounds 3'-deamino-3'-piperidino- and 3'-deamino-3'-morpholino derivatives of 13-hydroxycarminomycin or doxorubicin were prepared. Reduction of the antibiotic derivatives under mass spectrometry conditions was demonstrated.

Carubicin↗
PubMed1990

[Production and antineoplastic activity of new asymmetric azines on the rubomycin base].

New alkulidene hydrazones of rubomycin (daunorubicin) with the linear or branched chain of the carbon atoms were studied: rubomycin 13-(hexylidene-2")-hydrazone, rubomycin 13-(heptylidene-3")-hydrazone and rubomycin 13-(4"-methylpentylidene-2")-hydrazone. Alkylidene hydrazones of the formamidine derivatives were also studied: 13:cyclohexylidene hydrazone of 3'-desamino-3'-dimethylformamidine rubomycin and 13-(5"-oxypentyliden-2") hudrazone of 3'-desamino-3'-dimethylformamidine rubomycin. The latter two alkylidene hydrazones were modified twice. It was found that after a single intravenous administration to tumor-free mice the new substance had the same or lower toxicity as compared to that of rubomycin. Antitumor activity of the substances against lymphosarcoma LIO-I was studied comparatively with that of the initial rubomycin. It was shown that the molecule modification at C-13, as well as simultaneous modification at C-13 and the sugar amino group resulted in lowering of the antitumor activity in comparison to that of the starting rubomycin.

Animals↗
PubMed1989

[Derivatives of daunorubicin containing an inosine fragment].

Condensation of daunorubicin or its (13 R, S)-dihydro derivative with inosine dialdehyde in the presence of NaBH3CN yielded novel derivatives of anthracycline antibiotics with incorporated inosine residue: 3'-deamino-3'-[(2" R)-(hypoxanthyl-9)-(6" S)-hydroxymethylmorpholino-N4"]- daunorubicin and (13 R,S)-dihydro-3'-deamino-3'-[(2" R)-(hypoxanthyl-9)-(6" S)- hydroxymethylmorpholino-N4"]-daunorubicin. The compounds did not inhibit growth of Bacillus mycoides and were less cytotoxic in vitro and less toxic in vivo than the parent antibiotics.

Antibiotics, Antineoplastic↗
PubMed1989

[Modification of eremomycin by amine groups].

Possible modification of eremomycin, a novel glycopeptide antibiotic by the amine groups with acylating agents such as Ac2O/MeOH and CH3(CH2)7COCl/Et3N and alkylating agents such as CH3CHO, NaBH and NaBH3CN was studied. N-Acetyl, N,N'-diacetyl. N-pelargoil, N-ethyl, N,N'-diethyl and N,N',N"-triethyl derivatives of eremomycin were prepared. Their structure was asserted and the order of the substitute introduction was determined. The antimicrobial activity against Bacillus subtilis and Staphylococcus aureus was assayed. It was found that with introduction of the ethyl substitutes to the eremomycin molecule the antibiotic activity lowered insignificantly whereas the acylation resulted in its decreasing by 1-2 orders.

Acylation↗
PubMed1988

[New derivatives of carminomycin and rubomycin].

For preparing new semisynthetic analogs of anthracycline antibiotics, hydrolysis of 13-dimethylketals of 14-bromrubomycin and 14-brom-arminomycin in solution of diluted hydrochloric acid was studied. It was shown that such hydrolysis yielded 14-chlorrubomycin and 14-chlorcarminomycin. Conditions for separating the mixture of 14-chlor- and 14-bromrubomycins and the mixture of 14-chlor- and 14-bromcarminomycins by HPLC were developed. Interaction of 14-chlorine derivatives of rubomycin and carminomycin with potassium formate in the presence of the crown ether yielded 14-formyloxy derivatives of rubomycin and carminomycin. Interaction of rubomycin and carminomycin with formic acid in the presence of N-oxysuccinimide and dicyclohexylcarbodiimide resulted in formation of N-formyl derivatives of rubomycin and carminomycin.

Carubicin↗
PubMed1987

[Synthesis and antitumor action of 14-N-substituted derivatives of rubomycin and karminomycin].

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.

Animals↗
PubMed1982

[Synthesis and properties of the N-ethyl derivatives of carminomycin and rubomycin].

N-Monoethyl derivatives of carminomycin, rubomycin, 13-dihydrocarminomycin and 13-dihydrorubomycin were synthesized by condensation of their amino groups with acetic aldehyde in the presence of sodium boron hydride. The respective N,N-diethyl derivatives of the antibiotics were formed as by-products of the reaction. New compounds such as N-ethylcarminomycin, N,N-diethylcarminomycin, N-ethyl-13-dihydrocarminomycin, N,N-diethyl-13-dihydrocarminomycin, N-ethylrubomycin and N-ethyl-13-dihydrorubomycin were synthesized. Antibacterial activity of N-ethyl- and N,N-diethyl derivatives of carminomycin and rubomycin determined with the use of Bac. mycoides as the test microbe was 40-50 per cent and that of N-ethyl- and N,N-diethyl-13-dihydro-derivatives was 15-30 per cent of the activity of the respective antibiotics, carminomycin and rubomycin.

Alkylation↗