Relationship between fungistatic activity and structure in a series of simple aromatic compounds

The fungistatic activity of 127 benzene derivatives is reported and their behaviour related to structure and, in less detail, to solubility. The aromatic nucleus is more effective than its saturated counterpart. The effect of hydrophilic and nitro groups substituted in the benzene ring can differ markedly according to the position of substitution relative to groups already present. Halogen substitution is generally beneficial and is less affected by position. Nuclear substituted 4‐hydroxyhenzoates seem to behave biologically as substituted benzoic acids rather than as substituted phenols. The introduction of alkyl groups and alkyl esterification and etherification are generally beneficial, although the increased activity usually approaches an upper limit in the alkyl series relatively early (three to six carbon atoms). The carboxyl structure of the add and ester appears to be important since the analogous carbonyl compound is definitely less active. Methylene groups between the benzene nucleus and the carboxyl group lower effectiveness. Although there is evidently a general trend between inhibitory activity and decreasing water solubility, data available for 34 compounds show many deviations from a simple linear relationship between the logarithms of both properties. An approximate ratio between solubilities in ethanol and water (available for 23 compounds) provides a rather more significant relationship. There remain discrepancies, however, for the one organism, as well as between organisms, that suggest the operation of more specific factors than those covered in simple solubility data.