STRUCTURE AND ACTIVITY 461 



Table 1. Homologous Series and Fungistatic Activity 



Series 

 Saturated aliphatic alcohols (99) 

 Saturated aliphatic alcohols (110) 

 N-alkylpyridines (230) 

 N-alkyl-a-bromoacetamides (221) 

 Fatty acids (295) 

 Fatty acids (350) 

 Fatty acids (456) 

 Aliphatic amines (110) 

 Nicotinic acid esters (177) 

 2-Alkyl-l-hydroxyethylimidazolines 



(437) 

 Omega-(2-naphthyloxy)-K-alkyl- 



carboxylic acids (55) 



ably more specific in their action. But in both types — specific and 

 non-specific — the homologous series effect is evident. Gross activity, 

 therefore, depends in part on chemical potential, and again we are 

 dealing with a distribution function of some kind. Whether this dis- 

 tribution is between cell and environment, i.e., is a function of per- 

 meability, or whether some more subtle partition is decisive, cannot 

 at present be determined. 



In general, compounds of this type with branched chains are less 

 toxic than would be anticipated from their molecular weight alone. 

 Evidence for this generalization is reviewed by Horsfall (174). 



Data on bacteria illustrate a "quasi-specificity" (202): the carbon 

 chain length for optimum toxicity depends to a considerable extent on 

 the test organism. 



Competitive Inhibition. At the other extreme from structurally 

 non-specific inhibitors lies a group of poisons of extreme specificity. 

 These may be detected operationally by the fact that over some range 

 of concentration they compete with a cell metabolite. The theory and 

 known examples have been considered extensively in the literature 

 (277, 353, 454, 455). Of the chemotherapeutic agents, the sulfonamides 

 are the classical example (450). Some at least of the sulfonamides are 

 toxic to certain fungi (393, 449), and the available data (40, 92, 98, 

 147-149, 365, 393, 410, 449) indicate that, as in bacteria, sulfanilamide 

 competes with p-aminobenzoic acid for an essential cell reaction. Sul- 

 fanilamide is, however, not strongly fungitoxic (203). 



Competitive inhibition in fungi is also demonstrable with metabolite 



