posted on 2021-03-24, 18:20authored byShuyan Zhao, Guishan Lin, Wengui Duan, Qianan Zhang, Yinglan Huang, Fuhou Lei
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, 1H NMR, 13C
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.