QUINONES, ETC. 477 



dryl groups for their activity or known to be inhibited by sulfhydryl 

 reagents are, it is true, inhibited in vitro by quinones and naphtho- 

 quinones (113, 159, 21 1, 213, 228, 319, 320, 364) and protected from this 

 inhibition by thiols (319). However, a series of investigations shows, 

 first, that quinones inhibit enzymes other than sulfhydryl-dependent 

 types and, second, that the order of effectiveness of different quinones 

 as enzyme inhibitors is not correlated with their antimicrobial activity 

 (163-171). It is also to be noted that quinone toxicity to Gram-positive 

 bacteria is not antagonized by thiols (121). 



These considerations indicate that some other reaction with essential 

 proteins should be considered, possibly an inactivation of amino groups. 

 For the present, it is not possible to specify any particular ultimate site 

 of action for the quinones, and the evidence suggests that they may be 

 general rather than specific enzyme inhibitors comparable to the heavy 

 metals. 



The relation of structure to fungistatic activity in the quinones is re- 

 viewed by McNew and Burchfield (266). Toxicity generally decreases 

 in the series naphthoquinone > phenanthraquinone > benzoquinone 

 > anthraquinone. Halogenation improves effectiveness; the effect of 

 other substituents depends upon specific type and position. Compari- 

 son of the effect of structure on inhibition of amylases reveals several 

 instances in which a given structural feature affects fungitoxicity in one 

 way, enzyme inhibition in another (320). Among the naphthoquinone 

 antimalarials, activity is generally correlated with low water solubility; 

 that is, not only a reactive grouping but also some non-polar properties 

 are essential (105). 



Although some quinones are natural products of fungi and could in 

 principle participate in terminal respiration (Chapter 6), there is as 

 yet no firm evidence that fungitoxic quinones act as metabolite ana- 

 logues, although, as mentioned earlier, their action may be reversed by 

 natural quinones. 



Non-quinonoid a,/3-unsaturated ketones are not so active as the qui- 

 nones against fungi; many, however, are antibacterial. Several, e.g., 

 patulin and penicillic acid, appeared first as antibiotics produced by 

 fungi. These compounds inhibit sulfhydryl enzymes, and their inhibi- 

 tion of both isolated enzymes and intact cells is reversed by thiols. 

 Consequently, it is believed that antibacterial action depends upon 

 some reaction, perhaps addition across the reactive double bond, with 

 sulfhydryl groups (122, 123, 351). Patulin, however, does not inhibit 

 urease, a sulfhydryl enzyme (168), and the action of dehydroacetic acid 

 is not reversed by thioglycolate (451). 



Studies of the action of unsaturated compounds on Bolrytis allii and 



