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Biomedical subjects

I Kawamoto

Publications and source records attributed to I Kawamoto.

At least 37 records · Page 2Linked to original sources
PubMed1992

KS-505a, a novel inhibitor of bovine brain Ca2+ and calmodulin-dependent cyclic-nucleotide phosphodiesterase from Streptomyces argenteolus.

A novel compound, KS-505a was isolated from the culture broth of a strain identified as Streptomyces argenteolus A-2. The compound inhibited bovine brain Ca2+ and calmodulin-dependent cyclic-nucleotide phosphodiesterase with an IC50 value (the concentration causing 50% inhibition) of 0.065 microM. The compound around that concentration had little or no effect on heart calmodulin-dependent and -independent cyclic-nucleotide phosphodiesterases, and protein kinase C.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1992

ES-242-1, a novel compound from Verticillium sp., binds to a site on N-methyl-D-aspartate receptor that is coupled to the channel domain.

A novel compound, ES-242-1, which binds to a site on N-methyl-D-aspartate (NMDA) receptor that is coupled to the channel domain, was isolated from the culture broth of a fungus, Verticillium sp. SPC-15898. ES-242-1 inhibited the [3H]thienyl cyclohexylpiperidine ([3H]TCP) binding to rat crude synaptic membrane fractions with an IC50 value of 116 nM, but did not inhibit the [3H]kainate binding to its receptor, which is another subtype of the excitatory amino acid receptor.

Animals↗
PubMed1990

Studies on penem and carbapenem. I. Syntheses and oral absorption of ester-type prodrugs of sodium (5R,6S)-2-(2-fluoroethylthio)-6-[(1R)-1-hydroxyethyl]penem-3-c arboxylat e.

Acyloxyalkyl esters (2a-d), alkyloxycarbonyloxyalkyl esters (2e-g) and (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester (2h) of (5R,6S)-2-(2-fluoroethylthio)-6-[(1R)-1-hydroxyethyl]penem-3- carboxylic acid (1) were synthesized. Enhanced oral absorption was observed in mice reflecting increased lipophilicity, compared with the parent 1 itself. Among them, the ester 2h showed a prolonged plasma level and a large area under the blood concentration-time curve (AUC) in rats. These ester-type prodrugs of penem 1 in phosphate buffer (pH 6.86) were much more stable than those of cephalosporins which easily degraded via isomerization to delta 2 cephalosporins.

Animals↗
PubMed1990

Studies on orally active cephalosporin esters. V. A prodrug approach for oral delivery of 3-thiazoliomethyl cephalosporin.

Oral delivery of 3-thiazoliomethyl cephalosporin 1 was attempted through a prodrug approach by applying thiamine chemistry. The 3-thiazoliomethyl group was modified to a ring-opened structure with no ionic charge, and the 4-carboxyl group was converted to pivaloyloxymethyl ester. Lipophilicity of the resulting derivatives (8-10) was suitable for passive absorption from the intestinal tract, and chemical stability in phosphate buffer solution (pH 6.86) was moderate. When administered orally to mice, these derivatives were mainly transformed to a novel 3-spiro cephalosporin 11, and desired reconversion to the 3-thiazoliomethyl cephalosporin was minor. Isomerization to delta 2-cephalosporin 14 was also observed. These results showed that the derivatives (8-10) tested in this study did not serve as orally active prodrugs of 3-thiazoliomethyl cephalosporin 1.

Administration, Oral↗
PubMed1989

Studies on orally active cephalosporin esters. II. Chemical stability of pivaloyloxymethyl esters in phosphate buffer solution.

The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH 6-8) were investigated. The degradation of the starting delta 3 cephalosporin ester proceeded mainly via isomerization to the delta 2 ester and subsequent hydrolysis to the delta 2 acid. Hydrolysis to the delta 3 acid (the parent acid) was very slow. Analysis of the rate constants indicated that the isomerization rate k12 was approximately equal to the apparent degradation rate of the delta 3 ester kdeg, and slower than the hydrolysis rate of the delta 2 ester k24. The isomerization process to the delta 2 ester was found to be the rate-determining step in the degradation of cephalosporin esters. The substituent at the C-3 position of the cephalosporins affected the degradation kinetics. The degradation was accelerated by increase of pH, buffer concentration and added protein.

Administration, Oral↗
PubMed1989

Studies on orally active cephalosporin esters. III. Effect of the 3-substituent on the chemical stability of pivaloyloxymethyl esters in phosphate buffer solution.

The effect of substituents at the C-3 position on the degradation kinetics of the pivaloyloxymethyl (POM) ester of delta 3 cephalosporin in phosphate buffer solution (pH 6-8) was investigated. In the degradation, the isomerization process to the delta 2 ester was the rate-determining step. In this study, the logarithm of the isomerization rate to the delta 2 ester (log k12) correlated with the carbon-13 nuclear magnetic resonance chemical shift difference value at C-3 and C-4 of the delta 3 ester (delta delta (4-3)). The energy level of the lowest unoccupied molecular orbital (LUMO) of the delta 3 esters also correlated with log k12. The electronic properties at the C-2 position had no effect on the isomerization reaction. On the other hand, the logarithm of the isomerization rate back to the delta 3 ester (log k21) correlated with the van der Waals volume (MV) of the 3-substituent. These results show that the substituent at the C-3 position influences mainly the electronic structure of the conjugated pi-bond system (C3 = C4 - C4 = O) and consequently affects the feasibility of isomerization to the delta 2 ester, i.e., the stability to degradation.

Administration, Oral↗
PubMed1989

KS-501 and KS-502, new inhibitors of Ca2+ and calmodulin-dependent cyclic-nucleotide phosphodiesterase from Sporothrix sp.

New inhibitors of Ca2+ and calmodulin-dependent cyclic-nucleotide phosphodiesterase, KS-501 and KS-502 were isolated from a fungus, Sporothrix sp. KAC-1985. Inhibitory concentration causing 50% inhibition (IC50) values of KS-501 and KS-502 for bovine brain enzyme were 1.8 and 4.3 microM, respectively. The compounds exhibited no or weak inhibition for calmodulin-independent cyclic-nucleotide phosphodiesterases and protein kinase C.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1989

Leinamycin, a new antitumor antibiotic from Streptomyces: producing organism, fermentation and isolation.

Leinamycin (DC 107) is newly discovered antitumor antibiotic with an unusual 1,3-dioxo-1,2-dithiolane structure. Five different producing strains were isolated from soils collected in Japan during 1985-1988 and were taxonomically assigned as Streptomyces. Fermentation studies indicate: Leinamycin was unstable in culture broth. A chemically defined medium could be designed for a preferable production. Streptomyces sp. S-140 grew on medium supplemented with Zn2+ and high porus polymer resin and accumulated 32 micrograms/ml of leinamycin. Improved isolation methods are described along with identification of mikamycin A co-produced with leinamycin by the strain S-140.

Antibiotics, Antineoplastic↗
PubMed1989

KS-504 compounds, novel inhibitors of Ca2+ and calmodulin-dependent cyclic nucleotide phosphodiesterase from Mollisia ventosa.

Novel inhibitors of Ca2+ and calmodulin-dependent cyclic nucleotide phosphodiesterase were isolated from the culture broth of a fungus, Mollisia ventosa KAC-1148. They were designated as KS-504a, KS-504b and KS-504d. A degradative product of KS-504a, called KS-504e, was also isolated and found to inhibit the enzyme. The 50% inhibitory concentration (IC50) values of KS-504a, KS-504b, KS-504d and KS-504e for bovine brain enzyme were 122, 109, greater than 500 and 139 microM, respectively.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1989

UCN-01 and UCN-02, new selective inhibitors of protein kinase C. I. Screening, producing organism and fermentation.

In the course of continued screening program for new selective inhibitors of protein kinase C (PKC), fermentation broths from over 5,000 soil isolates were screened for their inhibitory activity of PKC. HPLC analysis of active cultures revealed that five different strains (N-71, N-115, N-126, N-128 and N-139) of Streptomyces isolated from various local soil samples were found to produce staurosporine and related compounds. Of these strains, N-126, a high producing strain, was found to produce new selective inhibitors of PKC, UCN-01 and its stereoisomer, UCN-02. The pH control of fermentation resulted in an increase of the production of UCN-01 and UCN-02.

Alkaloids↗
PubMed1987

K-259-2, a new inhibitor of Ca2+ and calmodulin-dependent cyclic nucleotide phosphodiesterase from Micromonospora olivasterospora.

K-259-2, a new inhibitor of Ca2+ and calmodulin-dependent cyclic nucleotide phosphodiesterase, was isolated from the cultured broth of Micromonospora olivasterospora K-259. K-259-2 has an anthraquinone moiety in its structure. IC50 values for the effect of K-259-2 against Ca2+ and calmodulin-stimulated activity of the enzyme preparations from bovine brain and heart were 6.6 and 2.9 microM, respectively. On the other hand, basal activity (the activity in the presence of ethylene bis(oxyethylenenitrilo)tetraacetic acid (EGTA) instead of Ca2+/calmodulin) of the bovine brain enzyme, calmodulin-independent cyclic nucleotide phosphodiesterase from bovine heart, and protein kinase C from rat brain were inhibited by K-259-2 to a lesser extent with IC50 values of 27.4, 40.7 and 45.8 microM, respectively.

Anthraquinones↗
PubMed1986

DC-86-M, a novel antitumor antibiotic. I. Taxonomy of producing organism and fermentation.

A novel antibiotic, DC-86-M was isolated from the culture broth of a new isolate, DO-86, from the soil sample collected in Machida-shi, Japan. The producing organism was found to belong to Streptomycetes, for it formed aerial mycelia and chains of spores and its cell wall analyses revealed the presence of LL-diaminopimelic acid. The morphological, cultural and physiological characteristics of the strain DO-86 resemble closely those of Streptomyces luteogriseus and we concluded that the strain DO-86 could be designated as Streptomyces luteogriseus DO-86. The antibiotic was produced in the fermentation medium consisting of lactose 20 g, glucose 10 g, Pharmamedia 15 g, yeast extract 5 g, meat extract 10 g and CaCO3 2 g per liter of tap water.

Actinomycetales↗