Synthesis,3 D-QSAR and Molecular Docking of Hydroxamate Inhibitors
In search of natural renewable resource-based bioactive molecules,20 hydroxamate inhibitors were designed and synthesized using cinamaldehyde as the starting material.Their structures were characterized by FT-IR,1H NMR,13C NMR,and HRMS.And in vitro antifungal activity of the target compounds against 8 tested fungi was preliminarily evaluated by the agar dilution method.The bioassay results revealed that at the concentration of 50 mg/L,the target compounds exhibited certain inhibitory activity against 8 tested fungi,in which compounds 5r(R=o,o-Cl),5c(R=m-F),5b(R=o-F)and 5p(R=o,p-Cl)displayed better inhibitory activity of 93.3％,76.8％,75.3％and 72.3％,respectively,against P.piricola than that of the positive control chlorothalonil.At the same time,3D-quantitative structure-activity relationship(3 D-QSAR)study was carried out to explore the relationship of the molecular structures with their antifungal activity against P.piricola.And a reasonable and effective 3D-QSAR model(r2=0.980,q2=0.501)has been established.Besides,molecular docking was also performed to reveal the binding mode of the target compound 5r(R=o,o-Cl)with succinate dehydrogenase(SDH).It was found that compound 5r could be well embedded in the active pocket of the receptor protein.This showed a similar mode with SDH inhibitors(SDHI)carboxin.
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