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

Abstract

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.

3D-QSAR Combination with Molecular Dynamics Simulations to Effectively Design the Active Ryanodine Receptor Agonists against Spodoptera frugiperda

“…40 Various statistics were also calculated, including the cross-validated coefficient (q 2 ), the correlation coefficient (r 2 ), the optimum number of components (ONC), the standard error of estimate (SEE), and the F-statistic (F). 41 Molecular Dynamics Simulations. The S. frugiperda native RyR is a large and multifunctional homotetramer with more than 5000 amino acids; however, the diamide insecticides act only on the transmembrane region of the receptor, so it is necessary to investigate the interaction of diamide insecticides with the transmembrane region of the S. frugiperda native RyR to elucidate how the diamide insecticides work.…”

“…Here, the reliability of the models was analyzed by cross-validation of the leave-one-out (LOO) methodology . Various statistics were also calculated, including the cross-validated coefficient ( q 2 ), the correlation coefficient ( r 2 ), the optimum number of components (ONC), the standard error of estimate (SEE), and the F -statistic ( F ) …”

Computation-Directed Molecular Design, Synthesis, and Fungicidal Activity of Succinate Dehydrogenase Inhibitors

“…Rapid development of computer-aided drug design has promoted the progress of drug molecule research and provided some theoretical guidance for the rational new pesticide molecule design. − Density functional theory (DFT) is a quantum mechanical method for studying the electronic structure of multielectron systems, often used in condensed matter physics and computational chemistry . The combination of DFT and three-dimensional quantitative structure–activity relationship (3D-QSAR) to predict the bioactive conformation of pesticide molecules has become one of the effective methods for designing new pesticides. , Molecular docking is based on the principle of matching the geometric, energetic, and chemical environment of the receptor protein with small molecules to evaluate its binding and determine the optimal binding mode, similar to the bioactive conformation of small molecules under physiological conditions.…”