140 



C. L. GEMMILL 



VOL. 4 (1950) 



have shown that 2-methyl-i,4-naphthoquinone inhibits aerobic glycolysis in Schistosoma 

 mansoni, in vitro. Warren^^ has observed a similar effect in bone marrow. Meyerhof 

 AND Randall^ have found an inhibition of respiration, glycolysis and motility of 

 Trypanosoma equiperdum, in vitro, using potassium i,2-naphthoquinone-4-sulfonate. 

 Gemmill^* has studied the effects of various naphthoquinones on anerobic glycolysis 

 of frog muscle. His results are given in Table i. 



TABLE I 



NAPHTHOQUINONES WHICH INHIBITED GLYCOLYSIS IN CONCENTRATIONS OF I • lO" 



MOLAR OR LESS 



1. Sodium i,2-naphthoquinone-4-sulfonate 



2. 2-methyl-i,4-naphthoquinone 



3. Sodium 2-methyl-i,4-naphthohydroquinone diphosphate 



4. 2-hydroxy-3-methyl-i,4-naphthQquinone (Phthiocol) 



5. 2-methyl-4-amino-i-naphthol hydrochloride 



6. 2-hydroxy-i,4-naphthoquinone (Lawsone) 



7. 1,4-naphthohydroquinone 



8. 2-methyl-3-bromo-i,4-naphthoquinone 



9. 2-chloro-3-N-thiobutyl- 1 ,4-naphthoquinone 



10. 2-methyl-3-thioethyI-i,4-naphthoquinone 



1 1 . 2-hydroxy-3-cyclohexanol- 1 , 4-naphthoquinone 



In Table I may be seen several napthoquinones which are glycolytic inhibitors. 

 The relationship of concentration to inhibition by sodium i,2-naphthoquinone-4- 

 sulfonate may be seen in Fig. i. At low concentrations there is a slight stimulation of 

 glycolysis. As the concentrations increase there is a marked change in glycolysis with 

 practically complete inhibition occurring with concentration of 0.4-10"^ Molar. Some 



of the naphthoquinones which have vitamin 

 K activity also are inhibitors of anerobic 

 glycolysis: 2-methyl-i,4-napthoquinone, so- 

 dium 2-methyl-i, 4-naphthoquinone diphos- 

 phate and 2-methyl-4-amino-i-naphthol hy- 

 drochloride. Another interesting fact which 

 came out of this work was that the attach- 

 ment of a halogen in the 2 or 3 position 

 increased the inhibitory activity of these 

 compounds. 



Amidines and Related Compounds: His- 

 torically, the study of the chemotherapeutic 

 properties of the diamidine compounds was 

 a direct result of a search for agents which 

 would block the use of glucose by the try- 

 panosomes-^. The early discovery that deca- 

 methylene diguanidine hydrochloride (Syn- 

 thalin) was effective against certain trypan- 

 osomes led to a search for less toxic substances. 

 Out of this search came many guanidines, 

 isothioureas, amidines^^ and numerous aro- 

 matic diamidines, among them being stilb- 

 amidine and pentamidine. It was soon 



02 



0.6 1.0 



UlO'^molar 



Fig. I. The effects of increasing concen- 

 trations of sodium i,2-naphthoquinone-4- 

 sulfonate on glycolysis. Abscissae, i-io— ^ 

 Molar final concentration: ordinates, per 

 cent of normal glycolysis. 



References p. 142I143. 



