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Biomedical subjects

K Kobashi

Publications and source records attributed to K Kobashi.

At least 181 records · Page 10Linked to original sources
PubMed1980

Therapy for urolithiasis by hydroxamic acids. II. Urease inhibitory potency and urinary excretion rate of hippurohydroxamic acid derivatives.

The apparent I50 values of various hippurohydroxamic acids against urease activity of sword bean were mostly 0.5 to 2.0 microM regardless of hydrophobicity of their substituents. However, the marked increase of hydrophilicity caused by substitution of trimethoxy groups conspicuously decreased the inhibitory potency. Methylation at alpha-position of the hydroxamic acid group in these compounds remarkably decreased the inhibitory potency, probably owing to steric hindrance by the alpha-methyl group. Thenoyl-, furoyl- and nicotino-glycinohydroxamic acids which are bioisostereomers of hippurohydroxamic acid had I50 values of 0.64, 1.3 and 5.3 microM, respectively. Furthermore, the inhibitory potency of some substituted hippurohydroxamic acids against the ureolytic activity of intact Proteus mirabilis isolated from patients with urinary tract infection, were half to one-tenth of those against urease activity of sword bean. On the other hand, m- and p-nitro-, m- and p-methoxy-, m- and p-acetylamino-hippurohydroxamic acid and furoylglycinohydroxamic acid showed high urinary excretion rates of 14 to 16% of the doses administered orally to rats, while most of the others had excretion rates of about 3 to 5%.

Fabaceae↗
PubMed1980

Therapy for urolithiasis by hydroxamic acids. III. Urease inhibitory potency and urinary excretion rate of N-acylglycinohydroxamic acids.

Hydroxamic acid, a potent urease inhibitor, having a high urinary excretion rate is expected to be a therapeutic agent for urolithiasis caused by urea-splitting bacterial infection of the urinary tract. Twenty-one new derivatives of N-aliphatic-acylglycinohydroxamic acids (GHAs) were synthesized, and their inhibitory potencies against the urease activity of sword bean in a phosphate buffer and against the ureolytic activity of Proteus mirabilis in human urine, and their urinary excretion rates in rats were also measured for this purpose I50 values of most of GHAs against the urease activity of sword bean were about 1 to 10 microM and 2-ethyl-n-butyroyl GHA was the most potent inhibitor with the value of 0.79 microM. I50 values of most of the GHAs against the ureolytic activity of Proteus mirabilis were about 5 to 50 microM and n-nonaroyl GHA was the most potent inhibitor with the value of 3.6 microM. 2,2-Dimethylpropionyl GHA had the highest urinary excretion rate with the recovery of 11%. Routes of administration of 2,2-dimethylpropionyl GHA and sex of rats used did not affect the amount of urinary excretion at all. The results in this report suggest that DL 2-methyl-n-butyroyl, 2-ethyl-n-butyroyl and 2,2-dimethylpropionyl GHA are the most hopeful therapeutic agents for urolithiasis among them.

Animals↗
PubMed1980

Quantitative structure-activity relationships between hydroxamic acids and their urease inhibitory potency.

Quantitative structure activity relationships between physico-chemical properties of four series of more than sixty hydroxamic acids [R-(CONHCH2)n-CONHOH, R=aromatic or aliphatic, n=1 or 0) and their urease inhibitory activities were examined. The best improved regression equation primarily indicated that the inhibitory activities of hydroxamic acids were parabolically varied with the hydrophobic variable, pi of the R moiety and the optimal pi value was calculated to be 2.58. Furthermore, the inhibitory activities of congeners were found to be significantly affected by the B1 variable representing the minimum width of steric size of the R moiety. Besides, it was clarified by using two indicator variables that inhibitory activities were not affected by the R moiety, whether aromatic or aliphatic, but positively affected by the presence of the -CONHCH2-group between the R moiety and the hydroxamic acid group.

Chemical Phenomena↗
PubMed1980

Prevention of infected urinary stones in rats by urease inhibitor: a new hydroxamic acid derivative.

We tested the inhibitory power and urinary excretion of several derivatives of hippurohydroxamic acid, including some newly synthesized compounds. m-Methoxyhippurohydroxamic acid (UCD II) strongly inhibited urease activity and high urinary excretion after oral administration to rats. UCD II inhibited the alkalinization of infected urine in vitro and in vivo and prevented bladder stone formation when it was orally administered to rats with urinary tract infection caused by Proteus mirabilis. The clinical application of UCD II to the prevention of pathologic sequelae of urinary infection with urease-producing bacteria awaits evaluation of the safety of the compound.

Animals↗
PubMed1979

Urease-producing species of intestinal anaerobes and their activities.

Urease activities of anaerobic bacteria that constituted predominant gut flora were examined. It was demonstrated that some strains of Eubacterium aerofaciens, E. lentum, and Peptostreptococcus products produced urease. They were the most numerous species in human feces. All strains of Bifidobacterium infantis and some strains of Bacteroides multiacidus, B. bifidum, Clostridium symbiosum, Fusobacterium necrophorum, F. varium, Lactobacillus fermentum, Peptococcus asaccharolyticus, and P. prevotii produced urease. The optimum pH of the Lactobacillus urease was found to be 4.0, whereas the pH value of B. multiacidus urease was 8.0.

Anaerobiosis↗
PubMed1978

A new hydrolase specific for taurine-conjugates of bile acids.

Through the investigation of the bile acid-deconjugation activities of human intestinal anaerobes, a new enzyme was discovered in Peptostreptococcus intermedius which hydrolyzed specifically the taurine-conjugates, but not the glycine-conjugates of bile acids. However, the enzymes in Streptococcus faecalis and Lactobacillus brevis hydrolyzed chiefly the glycine-conjugates.

Bile Acids and Salts↗
PubMed1975

Inhibition of urease activity by hydroxamic acid derivatives of amino acids.

Hydroxamic acids have been reported to be potent and specific inhibitors of urease (EC 3.5.1.5) activity of plant and bacterial origin. The present investigation was performed on the inhibitory effect of hydroxamic acid derivatives of naturally occurring amino acids on the urease activity of the Jack Bean and the alimentary tracts of rats. Methionine-hydroxamic acid was the most powerful inhibitor (I50=3.9 X 10(-6) M) among nineteen alpha-aminoacyl hydroxamic acids. Phenylalanine-, serine-, alanine-, glycine-, histidine-, threonine-, leucine-, and arginine-hydroxamic acids followed, in order of decreasing inhibitory power. The inhibition proceeded with time at a comparable rate to fatty acyl hydroxamic acid inhibition. The I50 values of alpha-aminoacyl hydroxamic acids were found to be almost equal to those of the corresponding fatty acyl hydroxamic acids. This fact shows that the alpha-amino group did not affect inhibitory power. However, aspartic-beta-, lysine-, and glutamic-gamma-hydroxamic acids, in descending order, were much less inhibitory, probably due to the presence of a carboxyl or omega-amino group. Furthermore, the pH optimum of the inhibition shifted to lower pH in the presence of a carboxyl group, and to a higher pH in e presence of an amino group. The results suggest that the dissociation of an acidic or a basic group reduces the inhibitory power of hydroxamic acid. Hydroxamic acid inhibits urease activity with strict specificity, excpet for aspartic-beta-hydroxamic acid, which inhibited asparaginase competitively. Hydroxamic acid derivatives of amino acids inhibited not only the urease activity of the Jack Bean, but also that of the caecum and ileum parts of the rat intestine.

Amino Acids↗