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M N Preobrazhenskaya

Publications and source records attributed to M N Preobrazhenskaya.

At least 19 recordsLinked to original sources
PubMed2004

The interaction of per-O-acetylated acyclic 1-(1-butylindol-3-yl)-1-deoxy-ketoses with silylated uracil.

The per-O-acetylated open chain derivatives of 1-(1-butylindol-3-yl)-1-deoxy-1-L-sorbose and 1-(1-butylindol-3-yl)-1-deoxy-L-tagatose, which are readily available by alkaline degradation of 1-butylascorbigen followed by acetylation, were used in a nucleoside-type synthesis. The interaction of these ketoses derivatives with bis-(trimethylsilyl)-uracil yielded in each case a mixture of (E)-2,4,5,6-tetra-O-acetyl-1-(1-butylindol-3-yl)-1,3-dideoxy-3-(uracil-1-yl)-L-xylo-hexa-1-enitol and (E)-2,4,5,6-tetra-O-acetyl-1-(1-butylindol-3-yl)-1,3-dideoxy-3-(uracil-1-yl)-L-lyxo-hexa-1-enitol, which were separated by preparative HPLC. The deacetylation of each of these compounds by MeONa in MeOH produced a mixture of 1-(1-butylindol-3-yl)-1,3-dideoxy-4-O-methyl-3-(uracil-1-yl)-alpha-L-sorbopyranose and 1-(1-butylindol-3-yl)-1,3-dideoxy-4-O-methyl-3-(uracil-1-yl)-beta-D-fructopyranose, which were also separated by HPLC, the structures were confirmed by NMR.

Ketoses↗
PubMed2001

The formation of 2-hydroxy-4-hydroxymethyl-3-(indol-3-yl)-cyclopent-2-enone derivatives from ascorbigens.

A facile preparation is described of 3-(indol-3-yl)-2-hydroxy-4-hydroxymethylcyclopent-2-enone and its N-derivatives in 15-40% yields by the degradation of ascorbigen or its N-derivatives in a warm solution of L-ascorbic acid through a sequential domino reaction. The same cyclopentenone derivatives were obtained in 30-40% yields by the condensation of (N-alkylindol-3-yl)glycolic acids with ascorbic acid. 2,6-Dihydroxy-1-(indol-3-yl)hexa-1,4-diene-3-one and 2-hydroxy-4-hydroxymethyl-5-(indol-3-yl)cyclopent-2-enone were identified as intermediates in this reaction.

Ascorbic Acid↗
PubMed2001

Synthesis of hydrophobic N'-mono and N',N"-double alkylated eremomycins inhibiting the transglycosylation stage of bacterial cell wall biosynthesis.

A series of hydrophobic N'-mono and N',N"-double alkylated derivatives of the glycopeptide antibiotic eremomycin were synthesized by reductive alkylation after preliminary protection of the N-terminal amino group of the peptide backbone. The investigation of the antibacterial activity in vitro showed that N'-C10H21- and N'-p-(p-chlorophenyl)benzyl derivatives of eremomycin are the most active against vancomycin-resistant enterococci among the compounds obtained though they are less effective than the corresponding lipophilic derivatives of vancomycin. The introduction of two hydrophobic substituents led to a decrease in activity against both susceptible and resistant bacteria. The biochemical evaluation of the mode of action revealed that in addition to binding to D-Ala-D-Ala these compounds also have an alternative mechanism of action that does not require substrate binding.

Alkylation↗
PubMed2000

Structure-activity relationships in the series of eremomycin carboxamides.

A series of new carboxamides of the glycopeptide antibiotic eremomycin was synthesized and investigated in vitro. The goal of the study was the comparison of the influence of the substituents introduced onto the eremomycin skeleton on the activity of these compounds against vancomycin susceptible and resistant bacterial strains. Eremomycin amides derived from amines with small substituents (C0 approximately C4) demonstrated antibacterial activity against vancomycin susceptible strains similar to that of the parent antibiotic and were inactive against vancomycin resistant strains. The derivatives of alkylamines with linear lipophilic substituents (like C10H21) were active against VanA and VanB enterococci strains with the scope of activity similar to that of N'-decyl or 7d-CH2NH-decyl eremomycins described earlier. Eremomycin amides of 5-methoxy- and 5-benzyloxytryptamine were active both against vancomycin susceptible and resistant strains. The introduction of a spacer (lysine or piperazine) between the decyl and antibiotic moieties did not seriously influence antibacterial properties of the compounds in comparison with the corresponding derivatives without a spacer. The most active carboxamides are of interest for secondary modifications of the antibiotic.

Anti-Bacterial Agents↗
PubMed1999

Chemical modification of antibiotic eremomycin at the asparagine side chain.

AA3-Carboxyeremomycin 2, obtained by selective hydrolysis of antibiotic eremomycin was used as a starting compound for the eremomycin chemical modifications at the asparagine side chain to be transformed into eremomycin AA3, AA7 bis-amides (3a-c). Bis-benzylamide 3b displayed an activity (8 microg/ml) against an E. faecium VanA strain.

Anti-Bacterial Agents↗
PubMed1998

Mono and double modified teicoplanin aglycon derivatives on the amino acid no. 7; structure-activity relationship.

A series of 7d-aminomethylated derivatives (mono modified) and their amides (double modified) at the amino acid No. 7 of teicoplanin aglycon were prepared with the aim of obtaining activity against vancomycin-resistant VanA enterococci. Among mono modified compounds, the 7d-n-decylaminomethyl derivative was the most active against VanA enterococci (4 micrograms/ml). Amides of the latter with 3-dimethylamino-propylamine or methylamine were found to be up to four times more active against glycopeptide-susceptible Gram-positive bacteria, and up to four times less active against VanA enterococci than the starting compound.

Anti-Bacterial Agents↗
PubMed1997

A new type of chemical modification of glycopeptides antibiotics: aminomethylated derivatives of eremomycin and their antibacterial activity.

A series of derivatives of eremomycin aminomethylated at the 7d position of the resorcinol ring of the amino acid No. 7 was prepared by interaction of eremomycin with formaldehyde and various primary and secondary amines and ammonia. The most active compound obtained was 7d-decylaminomethyl derivative, whose minimal inhibitory concentrations for clinical isolates of staphylococci are 2 approximately 8 times lower than those of the parent antibiotic. 7d-Decylaminomethyl derivative was also active against vancomycin-resistant VanA enterococci (8 microg/ml) and Neisseria gonorrhoeae (16 microg/ml).

Anti-Bacterial Agents↗
PubMed1997

Substitution of amino acids 1 and 3 in teicoplanin aglycon: synthesis and antibacterial activity of three first non-natural dalbaheptides.

The replacement of amino acids 1 and 3 of glycopeptide antibiotics (dalbaheptides) with new amino acids or other chemical entities suitable to interact with both glycopeptide-resistant (D-Ala-D-Lactate) and susceptible (D-Ala-D-Ala) targets is one of the chemical strategies currently followed to pursue activity against highly glycopeptide-resistant VanA enterococci while maintaining activity against glycopeptide-susceptible Gram-positive bacteria, particularly methicillin-resistant staphylococci. As a preliminary approach, the substitution of amino acid 1 of deglucoteicoplanin (TD) with D-lysine or D-methylleucine and of its amino acid 3 with L-phenylalanine or L-lysine was investigated. In this paper, the synthesis and in vitro antibacterial activities of first non-natural dalbaheptide methyl ester aglycons MDL 63,166 (D-Lys1-Phe-3-TD-DHP-Me), MDL 64,945 (D-Lys1-Lys3-TD-DHP-Me), and MDL 64,468 (D-MeLeu1-Lys3-TD-DHP-Me) are described. These compounds, which were obtained from intermediate TD-derived tetrapeptide methyl ester (TDTP-Me) according to a 9-step overall procedure, had excellent anti-staphylococcal activity. The most active derivative against staphylococci, MDL 64,945 (MIC: 0.063 microgram/ml for S. aureus, S. epidermidis and S. haemolyticus) was inactive against VanA enterococci, while MDL 63,166 and MDL 64,468 were somewhat active against VanA strains of E. faecalis; MDL 64,468 was also moderately active against one VanA isolate of E. faecium and had marginal activity as TD against E. coli.

Anti-Bacterial Agents↗
PubMed1996

A modification of the N-terminal amino acid in the eremomycin aglycone.

An Edman degradation of the antibiotic eremomycin aglycone produced the corresponding hexapeptide, which was aminoacylated with D-lysine, D-histidine or D-tryptophan derivatives to give new heptapeptide analogs of the eremomycin aglycone. The aminoacylation of the eremomycin aglycone produced an octapeptide analog. The substitution of D-lysine for the N-terminal N-methyl-D-leucine does not seriously affect the in vitro antibacterial properties of the eremomycin aglycone whereas the heptapeptides with the N-terminal D-tryptophan or D-histidine moieties and the octapeptide with the N-terminal D-lysine are practically devoid of the antibacterial properties.

Anti-Bacterial Agents↗
PubMed1996

Carboxamides and hydrazide of glycopeptide antibiotic eremomycin. Synthesis and antibacterial activity.

Carboxamides and hydrazide of glycopeptide antibiotic eremomycin were obtained by a direct reaction of the carboxy group of eremomycin with an appropriate amine or hydrazine using diphenyl phosphorazidate as a condencing agent. Eremomycin hydrazide was also obtained by hydrazinolysis of the eremomycin methyl ester. Use of dicyclohexylcarbodiimide or 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide for amidation led to the corresponding eremomycin ureides. The ESI-MS data indicate that eremomycin and its amides exist as dimers. The carboxamide, methylamide and benzylamide of eremomycin were as active against Gram-positive bacteria as the parent antibiotic, and the methylamide, benzylamide and hydrazide were almost an order of magnitude more active than eremomycin against Staphylococcus epidermidis clinical isolates in vitro. Amide of eremomycin as well as ureides were devoid of histamine liberating properties, which demonstrates that protection of the carboxyl group leads to a decrease in the allergenic properties.

Amides↗
PubMed1995

Polyfunctional indole-3-carbinol derivatives: 1-(indol-3-yl)glycerols and related compounds, beta-hydroxytryptamines and ascorbigens. Chemistry and biological properties.

Earlier interaction of indole-3-carbinols with L-ascorbic acid and chemical and biological properties of formed 2-skatylderivatives of L-ascorbic acid (ascorbigens) were discussed. In this presentation the properties and stereochemistry of products of interaction of polyfunctional biologically important indole-3-carbinols (indoleglycerol analogs and beta-hydroxytryptamine derivatives) with L-ascorbic acid are investigated. Biological significance of this reaction is discussed.

Animals↗
PubMed1994

Selective killing of tumor cells in vitro by immunotoxin composed of antitumor antibiotic streptonigrin and polyclonal specific antibodies.

Streptonigrin N-hydroxysuccinimide ester (STN-COONSu) was obtained by carbodiimide synthesis. Poly-L-lysine (PLL) was loaded with STN-COONSu and conjugated to polyclonal rabbit immunoglobulin G (IgG) activated with sodium periodate. Non-specific IgG and IgG against Ehrlich carcinoma cells were used to construct non-specific and specific immunotoxins. Immunotoxins contained 100 molecules of streptonigrin per 1 molecule of IgG. The streptonigrin concentration that caused 50% of inhibition of [3H]thymidine incorporation in Ehrlich carcinoma cells (IC50) was 0.8 micrograms/ml for specific immunotoxin, 16 micrograms/ml for non-specific immunotoxin, and 20 micrograms/ml for the poly-L-lysine-streptonigrin conjugate (PLL-STN) used as the initial water-soluble form of antibiotic. Our results demonstrate that the toxicity for target cells of streptonigrin conjugated to specific IgG was 25 times higher than that of the initial water soluble form of antibiotic. This specific immunotoxin was non-toxic for non-target cells.

Animals↗
PubMed1994

Modification of glycopeptide antibiotic eremomycin by the action of alkyl halides and study on antibacterial activity of the compounds obtained.

Alkylation of glycopeptide antibiotic eremomycin by the action of different alkyl halides leads, depending on the structure of alkyl halides used, to eremomycin derivatives of six types; alkylated at the N-terminus, quaternary compounds at the N-terminus, eremomycin esters, esters of eremocycin alkylated at the N-terminus, esters of eremomycin quaternised at the N-terminus, esters of eremomycin alkylated both at the N-terminus and at the aminogroup of disaccharide branch. Five compounds demonstrated high antibacterial activity in vitro, N-allyleremomycin and methyl ester of N,N-dimethyleremomycin being at least as good as the parent eremomycin.

Amino Acid Sequence↗
PubMed1993

Ascorbigen and other indole-derived compounds from Brassica vegetables and their analogs as anticarcinogenic and immunomodulating agents.

Searches for the natural compounds that determine the anticarcinogenic properties of a cruciferous-vegetable diet, revealed the products of alkaloid glucobrassicin biotransformations; among these, ascorbigen, an indole-containing derivative of L-ascorbic acid, was found to be the most abundant. Study of chemical properties of ascorbigen showed that it is capable of different transformations in acidic (including gastric juice) and slightly alkaline (including blood) media. The stable and unstable products of ascorbigen transformation determine the biological properties of the compound. The most important product of ascorbigen transformation in gastric juice is 5,11-dihydroindolo[3,2-b]-carbazole, with a binding affinity to the Ah receptor only 3.7 x 10(-2) lower than that of tetrachlorodibenzodioxin. This compound may be responsible for modifying P450 enzyme activities. Ascorbigen and its analogs are available synthetically. Their biological evaluation showed that some of the compounds of these series are immunomodulators. The most active is N-methylascorbigen, which demonstrates therapeutic effects (inhibition of tumor growth, protection of animals from bacterial and viral infections). The immunomodulatory activity of natural ascorbigen may be an additional factor of importance for the anticarcinogenic properties of a cruciferous-vegetable diet.

Adjuvants, Immunologic↗
PubMed1993

Synthesis and biological activity of derivatives of glycopeptide antibiotics eremomycin and vancomycin nitrosated, acylated or carbamoylated at the N-terminal.

Nitrosation, carbamoylation or acylation of the glycopeptide antibiotics eremomycin or vancomycin produced series of derivatives substituted at the N-terminus of the peptides. Though the modified amino group in these derivatives is not capable of protonation, N-nitroso derivatives retain antibacterial activity in vitro and in vivo. N-Carbamoyleremomycin has low activity, and N-Cbz-eremomycin and N-Boc-eremomycin are devoid of antibacterial activity, both in vitro and in vivo.

Amino Acid Sequence↗