570 5. QUINONES 



(D) Methoxy groups generally lower the activity in the naphthoquinone 

 series and, although data are not available, the methoxylated benzoqui- 

 nones are never very active. 



(E) Hydroxylation of 1,4-napthoquinone in either the 2- or 5-position 

 leads to loss of activity, these compounds having only one tenth-one 

 fifth the activity of menadione, which is roughly equivalent to 1,4- 

 naphthoquinone. 



There seems to be no question but that the quinone structure is of im- 

 portance in the antifungal action, since the corresponding nonquinonoid 

 compounds are usually not as inhibitory. Gonzalez (1945) showed that 

 /?-methylnaphthalene is a much weaker inhibitor of Penicillium notatum 

 than is menadione. However, this does not imply that the quinone groups 

 are directly involved in the reaction with the target components of the 

 fungal cells. 



Inhibition of Yeast Growth 



With respect to sensitivity to the quinones in general, yeasts seem to 

 lie somewhere between the gram-positive and gram-negative bacteria but, 

 according to Woolley (1945 a), are much more inhibited than any bacteria 

 or fungus by 2,3-dichloro-l,4-naphthoquinone. Such high sensitivity was 

 not noted by Hoffmann-Ostenhof and Fellner-Feldegg (1949 a), but these 

 discrepancies are undoubtedly due to the different conditions under which 

 the yeast was grown. The most potent inhibitors of yeast in the survey 

 of the latter workers are naphthazarin and phthiocol, which are only 

 weakly inhibitory to most bacteria, whereas the methoxy derivatives appear 

 to be more effective against bacteria than yeast. The inhibitions of yeast 

 or-glycerophosphatase (Hoffmann-Ostenhof and Putz, 1948) and yeast 

 proteinase (Hoffmann-Ostenhof and Moser, 1948) were claimed to exhibit 

 some correlation with growth inhibition, but this is very doubtful (see 

 Table 5-2). The quinones interfere with phosphate uptake by yeast only 

 at high concentrations, 0.1 mM somewhat stimulating uptake and 1 mM 

 inhibiting after 3 hr (Hoffmann-Ostenhof and Kriz, 1950), and have little 

 effect or slightly stimulate lipid synthesis (Hoffmann-Ostenhof and Kriz, 

 1949 a). Yeast fermentation is generally accelerated by various quinones, 

 except at high concentrations, but there is some depression of respiration 

 at concentrations of 0.01-0.1 mM (Hoffmann-Ostenhof and Kriz, 1949 b). 

 However, there is no correlation between respiratory and growth inhibi- 

 tions; e. g., 2,3-dichloro-l,4-naphthoquinone inhibits less than 2-chloro- 

 1,4-naphthoquinone and 1,2-naphthoquinone, and to about the same ex- 

 tent as p-benzoquinone, toluquinone, and menadione. Lejhanec et al. 

 (1931) found that p-benzoquinone at 0.0184 mM increases respiration and 

 simultaneously depresses growth. No correlations between the effects on 

 growth and metabolism have been established. Menadione and ferricyanide 



