ANALOGUES 



The antagonism of the D-isomer was not due to mechanical displace- 

 ment of riboflavine from an enzyme system. 



Lmniflavine, the photolysis product of riboflavine, inhibited or 

 stimulated the utilisation of riboflavine or fiavine adenine dinucleotide 

 by L. helveticus, according to the relative amounts present. ^^ Inhibi- 

 tion by lumiflavine was much greater with fiavine adenine dinucleotide 

 than with riboflavine, suggesting that riboflavine may be attached to 

 the apo-enzyme before conversion to riboflavine phosphate or fiavine 

 adenine dinucleotide. 



Riboflavine was oxidised stoichiometrically to lumiflavine by 

 Pseudomonas rihoflavina, and this organism also attacked the ribityl 

 group of analogues of riboflavine. The oxidation was inhibited by 

 phenyl-4 : 5-dimethyl-isoalloxazine,2o but the inhibition was not com- 

 petitive, since it was not reversed by high concentrations of riboflavine. 

 Moreover, this compound had no antiriboflavine activity in rats. 



Many substances that exhibited antimalarial activity were found 

 to inhibit the growth-promoting effect of riboflavine on L. helveticus .^^ 

 These included mepacrine, 2-^-chloroanilino-, 2-(6'-bromonaphthyl- 

 2'-amino)-, and 2-^-chlorophenylguanidino-4-diethylaminoethylamino- 

 6-methylpyrimidine. This type of approach led to the elaboration of a 

 number of new antimalarials, but rather paradoxically the best of 

 these, proguanil, did not antagonise riboflavine. Isoalloxazines con- 

 taining a basic side-chain, e.g. 6 : 7-dimethyl-9-y-amino-j8-hydroxy- 

 propyl-is oalloxazine 



CHa-CHOH-CHaNHa 



CH 



had no antimalarial or bacteriostatic activity, and did not antagonise 

 the growth-promoting effect of riboflavine on L. helveticus or E. coli.^^ 



References to Section 19 



1. R. Kuhn and F. Weygand, Ber., 1934, ^7, 2084. 



2. P. Karrer, H. Salomon, K. Schopp, F. Benz and B. Becker, Helv. 



Chim. Acta, 1935, 18, 908. 



3. H. von Euler, P. Karrer, M. Malraberg, K. Schopp, F. Benz, B. 



Becker and P. Frei, ibid., 522. 



4. P. Karrer, H. von Euler, M. Malmberg and K. Schopp, Svensk. 



Kem. Tids., 1935, 47, 153. 



5. P. Karrer and F. M. Strong, Helv. Chim. Acta, 1935, 18, 1343. 



6. P. Karrer and T. H. Quibell, ibid., 1936, 19, 1034. 



14 209 



