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At least 19 recordsLinked to original sources
PubMed1977

Inhibition of the biosynthesis of leucomycin, a macrolide antibiotic, by cerulenin.

Cerulenin, an inhibitor of fatty acid synthesis, specifically inhibits the biosynthesis of leucomycin, a 16-membered macrolide antibiotic, in both growing cells and resting cells of Streptomyces kitasatoensis. In growing cells, the production of leucomycin was inhibited as long as cerulenin remained in the culture. In resting cells, 50 percent inhibition was achieved with a cerulenin concentration of 1.5 microgram/ml. Cells in which leucomycin synthesis was inhibited for 9 h remained capable of leucomycin synthesis upon removal of the inhibitor. Cerulenin specifically inhibits the incorporation of [14C]acetate into leucomycin but does not affect total protein or RNA synthesis. The uptake of [14C]acetate was not inhibited under conditions which completely inhibited the incorporation of acetate into leucomycin. Since cerulenin is known to block the condensation of malonyl-CoA subunits in the formation of fatty acids, it can be concluded that the aglycone of leucomycin is synthesized via the polyketide pathway by condensation steps similar to those involved in fatty acid biosynthesis.

Acetates↗
PubMed2003

Synthesis and biological evaluation of novel leucomycin analogues modified at the C-3 position. I. Epimerization and methylation of the 3-hydroxyl group.

The synthesis and biological evaluation of sixteen-membered macrolides modified at the C-3 position are described. 3-Epi-leucomycin A7 (9), 3-O-acyl-3-epi-leucomycin A7 analogues (11a-11e), 3-O-acylleucomycin A7 analogues (13b-13e) and 3-O-methylleucomycin analogues (16a, 16b and 22) were synthesized via fully protected intermediates (7, 5a, 5b and 20). After appropriate modification, subsequent deprotections were performed to furnish a variety of leucomycin analogues. Methylation of the 3-hydroxyl group was found to improve the pharmacoprofile of leucomycin antibiotics. 3-O-Methylrokitamycin (16b) showed enhanced antibacterial activity in vitro and 3,3''-di-O-methyl-4''-O-(3-methylbutyl)leucomycin V (22) exhibited improved metabolic stability in rat plasma in vitro.

Anti-Bacterial Agents↗
PubMed1977

Structure-activity relationships among the O-acyl derivatives of leucomycin. Correlation of minimal inhibitory concentrations with binding to Escherichia coli ribosomes.

The synthesis, antimicrobial activity, and binding to ribosomes of leucomycin and leucomycin derivatives are described. In general, the binding of the leucomycins and the leucomycin derivatives to ribosomes correlated with their antimicrobial activity. Some 2'-O-acyl derivatives apparently underwent gradual hydrolysis during antimicrobial assays, for their binding to ribosomes was poor compared to their relatively good antimicrobial activies. Correlation between antimicrobial activity and binding to ribosomes, their molecular site of action, provides some insight into the nature of the active molecular moieties.

Anti-Bacterial Agents↗
PubMed1981

9-epi-leucomycin A5. Synthesis and antimicrobial activity.

9-epi-Leucomycin A5 has been obtained from leucomycin A5 (I) by the following reaction sequence. Leucomycin A5 (I) was treated with Collins reagent (CrO3-pyridine) in the presence of water (13%) to provide 9-dehydroleucomycin A5 (II) in 95% yield. The formyl group was internally protected by the reaction of II with acetic anhydride-K2CO3 to afford 18,2'-di-O-acetyl-9-dehydroleucomycin A5-3,18-hemiacetal (III). Sodium borohydride reaction of II provided a 1 : 1 mixture of natural I and its 9-epimer, 9-epi-leucomycin A5 (IV), which were separated by silica gel chromatography. It was observed that the antimicrobial activities of both enantiomers were virtually identical with some tests strains but that of IV is reduced in comparison with I in some bacteria such as Staphylococcus epidermidis sp-al-1 and Streptococcus pyogenes N. Y. 5.

Bacteria↗
PubMed1982

Novel dimeric derivatives of leucomycins and tylosin, sixteen-membered macrolides.

The reductive amination of an aldehyde group on the aglycon moiety of leucomycins A3 and A5 and tylosin with sodium cyanoborohydride in the presence of NH(CH3)2 or NH2CH3 afforded the corresponding amine derivative. The use of NH3 as an amine source in the reduction of leucomycin A3 and tylosin afforded a novel dimeric derivative, 18,18'-dideoxo-18,18'-iminodileucomycin A3 and 20,20'-dideoxo-20,20'-iminoditylosin, respectively. The structures of the dimers were elucidated by field desorption mass spectral analysis. The dimeric derivative of tylosin possesses considerable antibacterial activity. The binding activity of the dimer of Escherichia coli ribosome was approximately the same as for tylosin.

Bacteria↗
PubMed1981

Acyl derivatives of 16-membered macrolides. II. Antibacterial activities and serum levels of 3"-O-acyl derivatives of leucomycin.

3"-O-Acylation of leucomycin A5 increased its in vitro antibacterial activity against sensitive microorganisms and also some resistant ones. An increased effect was particularly noted when an acetyl or propionyl group was introduced. On the contrary, acylation of the C-3 and C-9 hydroxyl groups reduced the antibacterial activity in vitro. Introduction of an acyl group at the C-3" hydroxyl group increased the serum level of the compound. The increase in serum level from 3"-O-acylation is higher than that from 3-O-acylation. The serum level of the 3"-O-propionyl derivative of leucomycin A5 was higher than that of the 3"-O-acetyl derivative. 3"-O-Propionylleucomycin A5 (5) was the derivative that showed the highest antibacterial activity and yielded the highest serum level among the derivatives examined.

Animals↗
PubMed1982

Binding of [3H]tetrahydroleucomycin A3 to Escherichia coli ribosomes and the effect of 3"-O-acyl derivatives of leucomycins on the binding.

The analysis of [3H]tetrahydroleucomycin A3 binding to Escherichia coli ribosomes are described. The dissociation constant for tetrahydroleucomycin A3 binding to ribosomes was 1.15 x 10(-8) M. One molecule of tetrahydroleucomycin A3 was bound to each 70 S ribosome (50 S subunit) as reported with erythromycin. The effect of leucomycins and their 3"-O-acyl derivatives on [3H]tetrahydroleucomycin A3 binding to ribosomes was examined. In general, 3"-O-acyl derivatives of leucomycins exhibited stronger antimicrobial activity against Gram-positive bacteria and weaker (or equivalent) activity against E. coli than their mother compounds. However, the affinities to ribosomes were approximately equivalent to those of the mother compounds, suggesting that Gram-positive bacterial cells are more permeable to 3"-O-acyl derivatives than to the mother compounds.

Escherichia coli↗
PubMed1976

Studies on the influence of leucomycine on the carbohydrate metabolism of the lens in vitro.

The influence of leucomycine (10(-5) M--5 X 10(-3) M) on enzyme activities, free adenine nucleotides, and some intermediates of glycolysis in bovine lenses has been investigated. After a 48 h incubation in TCM 199, 6 out of 9 enzymes activities tested were decreased. Concentrations of energy rich nucleotifes, glucose, fructose, and fructose-6-phosphate as well as those of fructose-1,6-diphosphate and lactate were also decreased, whereas adenine monophosphate was increased.

Adenosine Monophosphate↗