ANTIBACTERIAL ACTIVITY 557 



Page and Robinson (1943) studied 14 quinones against S. aureus and E. 

 coli and found no significant correlation with redox potential. They pointed 

 out that all highly active quinones have Eq values in the range from 

 — 0.10 to + 0.15 V but that not all the quinones in this range are potently 

 bacteriostatic. It was felt that the redox potential may be of some impor- 

 tance but is certainly not the dominant factor. One might add that it is 

 not necessarily justifiable to compare all types of quinone in this way since 

 they probably do not all act by the same mechanism; thus comparison of 

 benzo- and naphthoquinones may not be valid. If one considers only the 

 benzoquinones in their work, an increase in activity occurs as the potential 

 drops from + 0.29 to + 0.13 v, and then decreases as the potential drops 

 lower. However, examining other data (Geiger, 1946; Hoffmann- Ostenhof 

 and Fellner-Feldegg, 1949 b, and others), no correlation between activity 

 and redox potential is evident. The suggestion of Geiger (1946) that the 

 semiquinones are the active forms seems to have little support and there is 

 no obvious correlation between activity and semiquinone stability; indeed, 

 duroquinone, which is particularly stable in the semiquinone form, is often 

 quite a weak inhibitor. 



Bacterial oxidative metabolism involves natural quinones and it is con- 

 ceivable that inhibitory quinones displace or compete with them. Phthiocol 

 was originally isolated from mycobacteria in 1933, and Kimler (1950) 

 examined menadione as an analog of phthiocol to determine if it would 

 inhibit mycobacterial growth. However, he did not determine if the inhi- 

 bition can be overcome by phthiocol or any vitamin K. Odier (1949) could 

 detect no reduction of the inhibitory action of 2-hydroxy-3-chloro-l,4- 

 naphthoquinone on M. phlei by phthiocol. It is true that the mycobacteria 

 are rather resistant to phthiocol, and that growth is often stimulated by 

 this substance, but there is no good evidence that it participates in the 

 metabolism of this organism. In view of the recent discoveries in this field, 

 it appears that the time is ripe for a more detailed examination of this 

 question. 



Reaction of the quinones with SH groups has been postulated as a 

 mechanism for the bacteriostasis. Col well and McCall (1945) found that 

 the inhibition of the growth of E. coli by menadione, 3-methylmenadione, 

 and 6-methylmenadione can be reduced by thioglycolate, mercaptoethane, 

 and cysteine. The inhibition by 3-methoxymenadione, however, was not 

 affected. It should be clear by now that antagonism by thiols shows only 

 that the quinones can react with SH groups but does not prove that the 

 reaction occurs or is important in the bacteria. Geiger (1946) claimed that 

 thiols antagonize the actions of quinones on gram-negative bacteria but 

 not on gram-positive bacteria, but this was not confirmed by Hoffmann- 

 Ostenhof and Fellner-Feldegg (1949 b), who found thiols to reduce the 

 inhibition on all bacteria. We have noted that occasional results favor the 



