RIBOFLAVIN 675 



39. Of the substances listed, quinine and atebrin do not appear to be 

 specific in their action since riboflavin, though affecting the inhibition, 

 apparently does not act in a competitive manner. However, quinine, 

 atebrin, and other antimalarials do affect certain isolated enzyme systems 

 in which the riboflavin coenzymes function. 



6,7-Dichloro-9(D,r-ribityl)isoalloxazine [Dichloroflavin] . Noting that re- 

 placement of methyl by chloro substituents on the benzene nucleus of 

 aromatic compounds changes the crystallographic properties so little that 

 uninterrupted series of mixed crystals often result, Kuhn, Weygand, and 

 Moller 50 prepared 6,7-dichloro-9(D,l'-ribityl)isoalloxazine as a possible 

 competitive inhibitor of riboflavin in biological systems. The analogue, 

 which was the first antagonist of riboflavin to be reported, inhibits the 

 growth of Staphylococcus aureus and Streptobacterium plantarum, but 

 does not restrict the growth of yeast or Bacillus lactis acidi. Riboflavin 

 competitively prevents the inhibitory action of the analogue, and the 

 inhibition indices for half-maximum growth are 50, 70, and 280 for 



OH OH OH 

 CH 2 — C— C C CH 2 OH 



A k k 



ci— k^^Jl //C\ 



N C 



& 



dichloroflavin[6,7-dichloro-9(D,l'-ribityl)isoalloxazine] 



tests incubated 3, 4, and 6 days, respectively, with Staphylococcus aureus. 

 With Streptobacterium plantarum, similar inhibition indices are 25, 60, 

 130, and 165 for incubation periods of 2, 3, 4, and 6 days, respectively. 

 The inhibitory behavior of dichloroflavin has been explained on the basis 

 of the difference in the redox potentials of dichloroflavin, E = —0.095 V 

 (pH 7), and riboflavin, E =— 0.185 V (pH 7). The vitamin analogue 

 probably cannot participate in the oxidation-reduction reactions medi- 

 ated by the riboflavin coenzymes. 50 



Neither dichloroflavin nor its 5'-phosphate affect the activity in vitro 

 of D-amino acid oxidase from liver or xanthine oxidase from milk even 

 at concentrations 1000-fold greater than that of the riboflavin coen- 

 zyme. 56 



Isoriboflavin [5,6-Dimethyl-9(D,l'-ribityl)isoalloxazine]. An isomer of 

 riboflavin, 5,6-dimethyl-9-(D,r-ribityl)isoalloxazine, at levels of 2 mg 



