Design, Synthesis, and Antifungal Activity of Novel Longifolene-Derived Diacylhydrazine Compounds

Abstract

Succinate dehydrogenase (SDH) present in the inner mitochondrial membrane is an important target enzyme for the design of SDH inhibitor-type fungicides. Using SDH as the target enzyme, 22 novel longifolene-derived diacylhydrazine compounds were designed and synthesized using the renewable natural product longifolene as the starting material. Their structures were confirmed by IR, 1 H NMR, 13 C NMR, electrospray mass spectrometry, and elemental analysis. In vitro antifungal activity of the target compounds was preliminarily evaluated. As a result, some of them showed better or comparable antifungal activity than that of the commercial fungicide chlorothalonil, in which compound 5a had inhibitory rates of 97.5, 80.5, 72.1, and 67.1% against Physalospora piricola , Colletotrichum orbiculare , Alternaria solani, and Gibberella zeae , respectively, presenting excellent and broad-spectrum activity that deserved further study. Besides, a reasonable and effective three-dimensional structure–activity quantitative relationship model has been established. There was a significant positive correlation between the antifungal activity and the docking-based binding energy analyzed using Spearman’s rank correlation algorithm. Also, the simulative binding pattern of the target compounds with SDH was investigated by molecular docking study. Furthermore, the diacylhydrazine and phenol groups of the target compounds were proposed to be the potential pharmacophores by frontier molecular orbital analysis.

Synthesis, 3D-QSAR and Molecular Docking Study of Nopol-Based 1,2,4-Triazole-Thioether Compounds as Potential Antifungal Agents

“…The 3D-QSAR model was built using the CoMFA method of Sybyl-X 2.1.1 software to investigate the relationship between the antifungal activity and the compound structure according to our previous report ( Zhao et al, 2021 ). The 3D structures of compounds 5a-5r were built on the sketch module and minimized by the conjugate gradient method in the program based on the Tripos force field using termination convergence energy of 0.005 kcal/(mol*Å), a maximum of 1,000 iterations, and Gasteiger-Hückel charge as the parameters.…”

Synthesis and Biological Activities of Novel (Z)‐/(E)‐Anisaldehyde‐Based Oxime Ester Compounds

“…The inhibitory rate of the target compounds against the seedling‐growth of monocotyledon plant barnyard grass ( E. crusgalli ) was carried out according to our previous reported method [35] . By using TW‐80 as emulsifying agent to aid dissolution, the compound to be tested was made into emulsions with concentrations of 10 μg/mL and 100 μg/mL.…”

Design, synthesis, and antiproliferative evaluation of novel longifolene-derived tetraline pyrimidine derivatives with fluorescence properties

“…Based on our previous work in seeking bioactive compounds from sustainable abundant biomass resources, [24][25][26] in the search for new survivin inhibitors with fluorescence properties, a series of novel longifolene-derived tetralin pyrimidine compounds were designed by the fusion of longifolene-derived tetralin and pyrimidine ring and screened further by molecular docking using the survivin protein (PDB ID: 3UIH) as the target. The designed compounds were synthesized and characterized.…”