328 RIBOFLAVIN 



by the daily administration of 40 7 of riboflavin. Two milligrams of isori- 

 boflavin daily restricts the growth of riboflavin-deficient rats much more 

 than does the deficiency of the vitamin alone. ^^- In L. casei isoriboflavin 

 showed no signs of competitive inhibition of riboflavin.^" 



D-Araboflavin evidently is an antagonist of riboflavin. Two hundred 

 micrograms per day decreases the rate of growth of rats receiving 10 7 

 of riboflavin per day to such an extent that no growth takes place by the 

 third week.^^ 



Another strong antagonist of riboflavin is D-galactoflavin, 6 , 7-dimethyl- 



OHH H OH 



I I I 1 

 9-(D-l'-dulcityl)isoalloxazine, R— CH2— C— C— C— C— CH2OH. In a dose 



I I I I 

 H OHOHH 



of 2.16 mg. per day, it inhibits completely the response of the animals to 

 10 7 of riboflavin daily and markedly inhibits the response to 40 7 of vita- 

 min B2 daily. The inhibitory effect is almost, but not completely, prevented 

 by 200 7 of riboflavin daily. ^''^ 



Dichloroflavin, 6,7-dichloro-9-(D-l'-ribityl)isoalloxazine (I), inhibits the 

 growth of Staphylococcus aureus, Streptobactermm plantarum, and Bacillus 

 lactis acidi, but not of yeast. The inhibition is competitively prevented 

 by riboflavin. Dichloroflavin has an oxidation reduction potential of Eo = 

 -0.095 volt (pH 7); for riboflavin it is ^0 = -0.185 volt (pH 7). This 

 difference has been regarded as an explanation for the inhibitory behavior 

 of dichloroflavin; perhaps the vitamin analog cannot function like ribo- 

 flavin in the oxidation-reduction reactions which are catalyzed by the ribo- 

 flavin coenzymes.^°^'^ Twelve other halogen-substituted flavins with various 

 sugar chains in the 9 position have been found to be less effective as ribo- 

 flavin antagonists than dichloroflavin, tested with Streptobacterium plan- 

 tarum P 32.104 



The growth of Eremothecium ashbyii, which produces riboflavin, is in- 

 hibited by dichloroflavin, without reduction of its riboflavin production. ^"^ 

 Therefore, the inhibition of this microorganism probably is not to be as- 

 sociated directly with displacement of the vitamin. 



It has been shown that certain 9-substituted 6,7-dichloroisoalloxazines 

 are inhibitors of D-amino acid oxidase. ^"^ However, neither dichloroflavin 



i«2 G. A. Emerson uiid M. Tishler, Proc. Soc. Exptl. Biol. Med. 55, (1914). 



10^ G. A. Emerson, E. Wurtz, and O. H. Johnson, J. Biol. Chem. 160, 165 (1945). 



'03'' R. Kuhn, F. Weygand, and E. F. Moller, Ber. 76, 1044 (1943). 



104 F. Weygand, R. Lowenfeld, and E. F. Moller, Ber. 84, 101 (1951). 



105 W. H; Schopfer, Intern. Z. Vitaminforsch. 20, 116 (1948). 

 108 R. B. Barlow, ./. Chew. i:^oc. 1951, 2225. 



