530 



ANNALS NEW YORK ACADEMY OF SCIENCES 



It is, of course, always of interest to attempt a correlation between 

 chemical structure of inhibitors and enzyme action. In general, com- 

 pounds which resemble the substrate, chemically, inhibit enzyme action, 

 presumably by combining with the same chemical groupings on the 

 enzyme molecule. However, it must be stressed that other chemical 

 groups on the inhibitor molecule may influence this combination. The 

 evaluation of this influence requires considerable experimentation. In 

 the case of cholinesterase, relatively few data are available. 



Acetylcholine is a quaternary ammonium compound. A survey of 

 the inhibitors which we have discussed shows that, although no strict 

 correlation can be drawn, between structure and degree of inhibition, 

 the closer the inhibitor comes to possessing a completely alkylated 

 nitrogen grouping, the greater is its inhibition. Thus, prostigmine, one 

 of the most effective inhibitors, has a quaternary ammonium grouping. 

 Physostigmine has two tertiary amine groupings. Methylene blue, 

 which is also a potent inhibitor, may be considered to have a cjuater- 

 nary ammonium grouping. Thionin, which is the unalkylated con- 

 gener of methylene blue, is a less powerful inhibitor; about 20-100 

 times as great a concentration is needed to produce 50 per cent 

 inhibition. 



That an alkylated amino grouping is important in inhibition, seems 

 to be generally true. Thus, the pyrazolone derivatives (antipyrines), 

 morphine, caffeine, percaine, are all moderate inhibitors. Unalkylated 

 amino groupings tend to make a compound a poor inhibitor: for exam- 

 ple, diphenylamine does not inhibit at 2 X 10"* M. Acid groupings 

 (COOH, SO3, H, OH), apparently tend to negate the inhibiting power 

 of alkylated amino groups. Examples of this occur in the sulfon- 

 amides and the acid dyes. 



CH3 



CH3 O 



\ ^ 

 N-C-0- 



/ 



CH, 



/ 



-N\ 



CH3NH-C-O 



SO4 



CH3 

 CH3 



CH3 



CH, 



prostigmine 

 S 



CH3 CH3 

 physostigmine 



N' 



w 



N 

 methylene blue 



H2N 



