EFFECTS ON FUNGI AND YEASTS 561 



formis is so sensitive to temperature that 0.00057 mM menadione stim- 

 ulates at 60-10° and inhibits at 110-12°, other naphthoquinones exhib- 

 iting similar effects. Too little attention has been paid to these factors in 

 determining antifungal potencies. 



Relation of Growth Inhibition to Structure 



There is a wide range of susceptibility between the various fungi to a 

 particular quinone; e. g., some fungi are very sensitive to menadione or 

 2,3-dichloro-l,4-napthoquinone, and others are quite resistant, a range of 

 over 1000-fold sometimes being observed. This is in part due to the dif- 

 ferent experimental conditions,* but one would also expect fungi to ex- 

 hibit a wide response spectrum since they do not constitute a homogeneous 

 group of organisms. It is evident that some particular activity or mechanism 

 must be associated with certain quinones, inasmuch as they are so much 

 more potent than others for a single type of fungus; i. e., although the 

 quinone structure may be important, other factors markedly modify this 

 activity. It is difficult to make generalizations concerning the relation of 

 potency to structure, and there will always be exceptions to any rule, but 

 a few possible correlations will be mentioned. 



(A) In 9 of 10 fungi the quinone is more potent than the corresponding 

 hydroquinone, the relative potency ratio averaging 5. The difference here 

 appears to be greater than for the bacteria. 



(B) Addition of chlorine atoms strongly increases the potency. In the 

 benzoquinone series, the relative potency ratios for p-Q:diCl-p-Q:tetraCl- 

 p-Q are 1:5:13, and in the naphthoquinone series the ratios for 1,4-NQ:2- 

 Cl-l,4-NQ:2,3-diCl-l,4-NQ are 1:8:80, these figures being very rough ap- 

 proximations but indicative of the magnitude of the effects. Furthermore, 

 2,3-dichloro-l,4-naphthoquinone is around 25 times more potent than 

 chloranil. 



(C) The effects of methylation are not consistent. Toluquinone seems to 

 be generally less potent than p-benzoquinone, but xyloquinone is more 

 potent, a mean potency sequence of 1:0.64:14 being obtained from limited 

 data. There is so much variation between responses to 1,4-naphthoquinone 

 and menadione that the effect of the 2-methyl group cannot be definitely 

 stated. The potency ratio MD:1,4-NQ runs between 0.077 and 16.8. If 

 anything, menadione is usually somewhat less active. It may be noted that 

 2-chloro-l,4-naphthoquinone is around 16 times more potent than mena- 

 dione, although again there is considerable variation. 



* One notes that in the studies in which two or more fungi were tested, the sen- 

 sitivities do not vary nearly as much as between the values given by different in- 

 vestigators. 



