Screening of Oxygenated Aromatic Compounds for Potential Antifungal Activity against Geotrichum citri-aurantii through Structure–Activity Relationship Analysis

Sour rot caused by Geotrichum citri-aurantii (G. citri-aurantii) is responsible for huge economic losses during citrus fruit storage. However, the availability of chemical fungicides for controlling this disease is rather limited. In the present study, the antifungal activities of 25 oxygenated aromatic compounds against the mycelial growth of G. citri-aurantii were determined, and their corresponding structure–activity relationships were illustrated. Salicylaldehyde (pMIC = 2.689) possessed the strongest inhibitory effect on G. citri-aurantii growth, followed by thymol (pMIC = 2.478) and o-phthalaldehyde (pMIC = 2.429). Molecular electrostatic potential and molecular orbital analysis showed that the antifungal efficiency of test compounds was determined by the number and location of hydroxyl and aldehyde groups and the length of the ester chain. All compounds were selected for quantitative structure–antifungal activity relationship (QSAR) analysis. A three-dimensional-QSAR model of G. citri-aurantii inhibitors was established and demonstrated good predictive capability [comparative molecular field analysis, q 2 = 0.532, optimum number of components (ONC) =10, R 2 = 0.996, F = 560.325, standard error of estimation (SEE) = 0.034, and two descriptors; comparative similarity index analysis, q 2 = 0.675, ONC = 6, R 2 = 0.989, F = 263.354, SEE = 0.054, and five descriptors]. QSAR analysis showed that substitution at position 1 with hydrophilic and electron-withdrawing groups produced a hydrogen donor and thus improved the antifungal activity. In contrast, substitution at positions 4 or 5 with hydrophilic and electron-donating groups decreased its antifungal activity. These findings can provide theoretical guidance for preparing effective antifungal drugs for controlling sour rot in citrus.