Yong Li,Zhongfu Luo,Wenjing Liu,Wenzhang Chen,Jianta Wang,Gaofeng Zhu,Bing Guo,Lei Tang,Lingling Fan
Four series of novel 1,3,4-oxadiazole/1,2,4-triazole hybrids of phthalide derivatives were designed and synthesized to search for novel potential antifungal agents. Preliminary antifungal activity assay results showed that compounds 4 a , 4 b , 4 m , 5 b , 5 f , 5 h , and 7 h exhibited moderate to excellent inhibitory activity against some phytopathogenic fungi. Among them, compound 5 b displayed the most outstanding antifungal effects against V. mali and S. sclerotiorum , with the EC 50 mean of 3.96 μg/mL and 5.60 μg/mL, respectively, which was superior to those of commercial fungicides hymexazol and chlorothalonil. Furthermore, compound 5 b could completely suppress the spore germination of V. mali at a concentration of 10 μg/mL. Finally, molecular docking revealed that the potential target for the antifungal activity of compound 5 b was succinate dehydrogenase (SDH). This research provides novel candidate compounds for the prevention of phytopathogenic fungi. Graphical
Shiben Wang,Hui Liu,Kang Lei,Guangyong Li,Jun Li,Yuyu Wei,Xuekun Wang,Renmin Liu
In this study, a series of 3,4-dihydroquinolin-2(1 H )-one derivatives were designed and synthesized using two experimental models, namely maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ), to test the anticonvulsant activity of the target compound in vivo (i.p. in Kunming mice). The neurotoxicity (NT) of the target compound was measured by the rotating rod method (i.p. in Kunming mice). Six compounds with potential activity were selected from the two experimental models to test the 50% effective dose (ED 50 ). In vitro binding experiments with the GABA A receptor were also performed. The results of the pharmacological experiments showed that compound 7-((5-(pentylthio)-1,3,4-oxadiazol-2-yl)methoxy)-3,4-dihydroquinolin-2(1 H )-one ( 5b ) showed the best anticonvulsant activity (MES, ED 50 = 10.1 mg/kg; scPTZ, ED 50 = 9.3 mg/kg), which was superior to activities shown by carbamazepine and ethosuximide, and it also exhibited the most potent binding affinity to GABA A receptors (IC 50 = 0.12 μM). The GABA content in Wistar rat brains (i.p.) was also investigated, and the results showed that compound 5b may have a certain effect on the GABA system, as it increased the GABA concentration in the brain of rats. Molecular docking was used to study the binding mode of compound 5b and the GABA A receptor. Compound 5b showed significant interactions with residues at the benzodiazepines binding site on the GABA A receptor. The physicochemical and pharmacokinetic properties of the target compounds were predicted using Discovery Studio 2019 and ChemBioDraw Ultra 14.0.
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