ANTIBACTERIAL EFFECTS OF ESTERS OF GUANIDINO-ACIDS AND AMIDINO-ACIDS TRYPSIN-INHIBITORS

Inhibitory effects of various esters of trans-4-guanidinomethylcyclohe xanecarboxylic acid and the 4-tertbutylphenyl esters of amidinopiperid ine-4-alkanoic, trans-4-amidinocyclohexanealkanoic, trans-4-guanidinoe thylcyclohexanecarboxylic and trans-4-guanidinocyclohexanealkanoic aci ds, all trypsin inhibitors, on the growth off. coli, B. subtilis, S. a ureus and S. epidermidis were examined. 4-tert-Butylphenyl esters stro ngly inhibited the growth of E. coli and the order of the inhibitory e ffects correlated with that for the inhibitory effects on proteinase I n, which appears immediately before initiation of DNA synthesis in E. coil and closely correlates with the onset of DNA synthesis. No correl ation was observed between the inhibitory effects and K-i values for t rypsin. The 4-tert-butylphenyl esters also strongly inhibited B. subti lis, S. aureus and S. epidermidis, and the order, of the inhibitory ef fects on these bacteria roughly coincided with that on E. coli. The or der of the inhibitory effects of each ester, on these bacteria was S. epidermidis > S. aureus > B. subtilis > E. coil. Among the esters exam ined, the biphenyl ester of trans-4-guanidinoethylcyclohexanecarboxyli c acid was the most inhibitory on these four bacteria and proteinase I n. Hydrolysis of tert-butyloxycarbonyl-L-valyl-L-prolyl-L-arginine 4-m ethylcoumarin-7-amide, which is a substrate for proteinase In, in crud e extracts of E. coli, B. subtilis and S. epidermidis was examined. Th e order of this activity in these bacteria was E. coli > B. subtilis > S. epidermidis.