Structure-activity relationships in a series of new antifungal nitroalcohol derivatives

The structure-antifungal activity correlations of 23 new nitroalcohol derivatives (1-substituted-2-nitropropane-1, 3-diols, their ethers and esters) were investigated using a generalised quantitative structure-activity relationships (QSAR) method, combining Golender and Rozenblit's logico-structural approach and the Free-Wilson and Hansch analyses. Based on results obtained from principal component analysis, the in-vitro activities against Helminthosporium sativum, the inhibition of germination and of growth could be assumed to be governed by a common mechanism. It is suggested that the antifungal activity of the compounds studied is determined mainly by the presence or absence of an aromatic ring (unsubstituted, or bearing a hydrophobic group that is small in bulk and electron-attracting) at position 1, of a (potential) double bond between carbon atoms 1 and 2, and of an acyloxy group at position 3. Among these factors, the double bond seems to be the most important, and the mechanism of the antifungal action is probably dependent on the reactivity of this bond towards thiol groups of endogenous substances.