THE NICOTINIC ACID GROUP 615 



A number of analogues of nicotinic acid have been reported to be inac- 

 tive as inhibitory analogues of the vitamin. These include; 1,2-dinicotinyl- 

 hydrazine, 81 nicotinamide, 82 nicotinhydrazide, 2-fluoronicotinic acid, 83 

 6-fluoronicotinic acid, 83 5-bromonicotinic acid, and 5-bromonicotinamide. 



The synthesis of 5-fluoronicotinic acid and 5-fluoronicotinamide has 



-COOH F-f^,-CONH 2 



5-fluoronicotinic acid 5-fluoronicotinamide 



been recently reported, but the biological action of the analogues are not 

 as yet available. 84 Preliminary tests have indicated that these compounds 

 are the most effective nicotinic acid antagonists as yet reported. The 

 analogues, particularly the acid, inhibit a large number of bacteria at 

 relatively low inhibition indices. 85 



Natural Antagonisms Related to Nicotinic Acid. Pellagra has long been 

 associated with the eating of corn, and evidence has been presented which 

 indicates that nicotinic acid is required in higher amounts if corn is 

 included in the diet of animals. 81, 86, 87 In fact, rats which ordinarily do 

 not require nicotinic acid need either a supplement of nicotinic acid or 

 additional tryptophan in the diet to overcome the retardations of growth 

 resulting from the inclusion of corn grits in a low-protein diet. 88 Since 

 supplementary tryptophan administered either orally or subcutaneously 

 to the rat causes increased excretion of metabolites of the nicotinic acid 

 group, this animal appears to synthesize nicotinic acid from tryptophan. 89 

 Administered to patients with pellagra, tryptophan (6-g oral doses) 

 causes a remission of typical acute pellagrous lesions with increased 

 urinary excretion of N 1 -methylnicotinamide. 90 Tryptophan does not, how- 

 ever, affect the nicotinic acid requirement of many organisms, e.g., Tetra- 

 hymena geleii W 91 and most lactobacilli. Evidence has been presented 

 indicating that the conversion of tryptophan to nicotinic acid in the rat 

 is impaired by certain amino acids, such as glycine and threonine, by 

 tryptophan-free proteins, or by corn grits. 92, 93 However, the mode of 

 action of the responsible substances is largely unknown. In mice fed a 

 low-protein diet a weakly basic water-soluble substance which has been 

 concentrated about 100,000 times from corn causes a disease similar to 

 pellagra which is preventable or curable with nicotinamide. 94 Indoleacetic 

 acid has been reported to retard growth of rats in a manner similar to 

 corn, and its effect on growth is prevented by either nicotinic acid or 

 tryptophan. 95 Although other reports fail to confirm this effect of indole- 

 acetic acid, 69, 96 there appear to be naturally occurring materials which 



