330 



RIBOFLAVIN 



and of Walker carcinomas in rats deficient in riboflavin were reported. ^"^ 

 In some cases, the animals were rendered strongly deficient in riboflavin 

 by feeding one of the riboflavin antagonists, isoriboflavin, galactoflavin, or 

 diethylflavin, along with a diet deficient in riboflavin. The activity of di- 

 chloro-D-sorboflavin (II) shows that the mechanism of regression of the 

 lymphosarcoma need not necessarily occur through riboflavin inhibition. 



Lumiflavin, the photolysis product of riboflavin, is either an inhibitor or 

 a stimulator of the utilization of riboflavin or flavin adenine dinucleotide 

 by L. casei, depending upon the relative amounts of lumiflavin present. ^"^ 



The phenazine analog of riboflavin, 2,4-diamino-7,8-dimethyl-10-(D- 

 ribityl)-5 , 10-dihydrophenazine (1),^°^ antagonizes the action of vitamin 

 B2 in riboflavin-requiring bacteria. The dinitrophenazine derivative from 

 which I is prepared produces mild riboflavin deficiency in mice. Adequate 

 amounts of riboflavin overcome the effects of the compound. 



H3C 



H3C 



CH2(CHOH)3CH20H 



I 

 N NH, H3CO 



CH3 



NHCH(CH2) 3N(C 2H5) 2HCI 



II 



CI 



NH2 



Atabrin (Mepacrine) 



Many substances with antimalarial activity were found to inhibit the 

 growth-promoting effect of riboflavin on microorganisms, for instance mepa- 

 crine (atabrin) (II), ^^O' "^ substituted pyrimidines,^^^ and quinine. How- 

 ever there is no strong parallelism between the antimalarial and the anti- 

 vitamin function; for instance, proguanil (paludrine) does not antagonize 

 riboflavin. The structural similarity of certain antimalarials to the flavin 

 nucleus is probably not directly correlated to their antimalarial action."^ 



Mode of Action of Riboflavin Antagonists. ^^'^ At least three ways are pos- 



1" H. P. Morris and W. van B. Robertson, J. Natl. Cancer Inst. 3, 479 (1943); H. C. 



Stoerk and G. A. Emerson, Proc. Roc. Exptl. Biol. Med. 70, 703 (1943). 

 "8 H. P. Sarett, Federation Proc. 4, 101 (1945); J. Biol. Chem. 162, 87 (1946). 



109 D. W. Woolley, J. Biol. Chem. 154, 31 (1944); H. P. Sarett, J. Biol. Chem. 162, 

 87 (1946). 



110 J. Madinaveitia, Biochem. J. 40, 373 (1946). 



111 M. Silverman and E. A. Evans, Jr., J. Biol. Chem. 150, 265 (1943). 



112 F. H. S. Curd and F. L. Rose, /. Chem. Soc. 1946, 343, 362, 366, 370; A. R. Todd et 

 al., ibid, 1946, 357. 



113 L. Hellermann, A. Lindsay, and M. Bovarnick, J. Biol. Chem. 163, 553 (1946). 

 1" E. B. Kearney, J. Biol. Chem. 194, 747 (1952). 



