Therapy for urolithiasis by hydroxamic acids. III. Urease inhibitory potency and urinary excretion rate of N-acylglycinohydroxamic acids - PubMed (original) (raw)

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

K Munakata et al. J Pharmacobiodyn. 1980 Sep.

Abstract

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.

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