METABOLITE ANTAGONISTS 



235 



Martin et at. (1948) found desoxypyridoxine to be slightly more effec- 

 tive against pyridoxal than pyridoxine, when Saccharomyces cerevisiae 

 was used. 



Vitamin K antagonists. There are at least two naturally occurring 

 compounds which have vitamin K activity. Certain synthetic analogues 

 are used in medicine to replace the natural vitamins. All these com- 

 pounds are substituted 1,4-naphthoquinones. The structural formula 

 for vitamin K2 is given below: 



O 



O 



-CHs CH3 CH3 



I I 



-CHo— (CH=C— CH2— CH2)6— CH=C— CH3 



Vitamin K2 



Horsfall (1945) has reported 2-methyl-l,4-naphthoquinone to be a weak 

 fungicide, although this compound replaces natural vitamin K in medi- 

 cine. On the other hand, 2,3-dichloro-l,4-naphthoquinone (Phygon) is 

 a potent fungicide (Ter Horst and Felix, 1943). 



O 







— CHa 



O 

 2-Methy 1- 1 , 4-naphtho quinone 



—CI 

 —CI 



o 



2 , 3-Dichloro- 1 , 4-naphtho quinone 



Phygon may act as a fungicide by virtue of combination of the quinone 

 with free amine or sulfhydryl groups. This mechanism probably inac- 

 tivates certain enzymes noncompetitively. On the other hand, Phygon 

 is structurally related to vitamin K, and a competitive type of inhibition 

 should also be possible. Woolley (1945) investigated the inhibitory effect 

 of 2,3-dichloro-l,4-naphthoquinone and 2-methyl-l,4-naphthoquinone on 

 the growth of Saccharomyces cerevisiae and Endomyces vernalis. The first 

 compound was more toxic than the second. In less than toxic concen- 

 trations, the second compound partially overcame the toxicity of the 

 first. The amount of 2,3-dichloro-l,4-naphthoquinone required to 

 inhibit yeast (half maximum growth) was 1.7 jug per liter, while 230 ng 

 of 2-methyl-l,4-naphthoquinone were required to produce the same 

 amount of inhibition. Some of Woolley 's data are presented in Table 41. 

 Many potent antimalarial drugs are 1,4-naphthoquinone derivatives 

 (Fieser et al., 1948). 



It has been assumed in our discussion of the effects of antagonists on 



