592 5. QUINONES 



imine. Gray and Felsher (1945), on the basis of the xanthine oxidase inhi- 

 bition, injected p-aminophenol intravenously in a patient with urate gout, 

 administering 0.5-4 g daily, and observed no changes in either blood or 

 urine levels of urate, thus concluding that no inhibition occurs in vivo, 

 possibly due to the p-aminophenol remaining in the reduced form. Although 

 Bernheim et al. (1937) found no other dehydrogenases susceptible to 

 p-aminophenol, the endogenous respiration of rat liver suspensions is fairly 

 well inhibited (see accompanying tabulation), so that some enzyme in- 



volved in this uptake of oxygen must be sensitive. Unfortunately, one 

 does not know a great deal about the nature of such endogenous respiration. 



Effects on Proliferation and Growth 



Alcalay (1947 a) tested 18 naphthoquinones for bacteriostatic activity 

 (see Table 5-9), and found the most potent substance to be 2-amino-l,4- 

 napthoquinoneimine, bacteriostatic concentrations being in the range 

 0.01-0.04 mM and even E. coli being readily inhibited. It was found to 

 be much more toxic to mice, the maximal tolerated dose of 5 mg/kg causing 

 convulsions; the naphthoquinones were tolerated at doses of 35-400 mg/kg 

 (Alcalay, 1947 b). However, the naphthoquinoneimines have not been 

 thoroughly studied and it is impossible to assign a mechanism for this 

 growth inhibition. iV,iV,iV',iV'-Tetramethyl-p-phenylenediamine does not 

 appear to be virucidal or virustatic (Czekalowski, 1952). iV, A^-Dimethyl- 

 p-phenylenediamine at 0.22 mM causes a marked increase in the respira- 

 tion of sea urchin eggs, which is maximal at 2.2 mM, but in spite of this 

 the development proceeds normally (Runnstrom, 1932). This indicates 

 that it serves here as an oxidizable substrate and does not interfere with 

 important metabolic processes in the eggs (indeed such diamines are oxi- 

 dized quite rapidly at the pH of sea water in the absence of living material). 



