Abstract：
A series of new piperidine-4-carbohydrazide derivatives bearing a quinazolinyl moiety were prepared and evaluated for their fungicidal activities against agriculturally important fungi. Among these derivatives, the chemical structure of compound A45 was clearly verified by X-ray crystallographic analysis. The antifungal bioassays revealed that many compounds in this series possessed good to excellent inhibition effects toward the tested fungi. For example, compounds A13 and A41 had EC50 values of 0.83 and 0.88 μg/mL against Rhizoctonia solani in vitro, respectively, superior to those of positive controls Chlorothalonil and Boscalid (1.64 and 0.96 μg/mL, respectively). Additionally, the above two compounds also exhibited notable inhibitory activities against Verticillium dahliae (with EC50 values of 1.12 and 3.20 μg/mL, respectively), far better than the positive controls Carbendazim and Chlorothalonil (19.3 and 11.0 μg/mL, respectively). More importantly, compound A13 could potently inhibit the proliferation of R. solani in the potted rice plants, showing good in vivo curative and protective efficiencies of 76.9% and 76.6% at 200 μg/mL, respectively. Furthermore, compound A13 demonstrated an effective inhibition of succinate dehydrogenase (SDH) activity in vitro with an IC50 value of 6.07 μM. Finally, the molecular docking study revealed that this compound could be well embedded into the active pocket of SDH via multiple noncovalent interactions, involving residues like SER39, ARG43, and GLY46.
摘要：
制备了一系列带有喹唑啉基部分的新哌啶-4-碳酰肼衍生物，并评估了其对农业上重要的真菌的杀真菌活性。在这些衍生物中，化合物A45的化学结构由X-射线晶体学分析清楚地证实。抗真菌生物测定表明，该系列中的许多化合物对所测试的真菌具有良好至优异的抑制作用。例如,化合物A13和A41的EC50值分别为0.83和0.88μg/mL,分别,优于阳性对照的百菌清和Bocalid（1.64和0.96μg/mL，分别)。此外,上述两种化合物对黄萎病菌也表现出显著的抑制活性(EC50值分别为1.12和3.20μg/mL,分别)，远优于阳性对照多菌灵和百菌清(19.3和11.0μg/mL，分别)。更重要的是,化合物A13能有效抑制盆栽水稻中茄子的增殖，在200μg/mL时显示出良好的体内治疗和保护效率，分别为76.9％和76.6％，分别。此外，化合物A13在体外表现出对琥珀酸脱氢酶(SDH)活性的有效抑制,IC50值为6.07μM。最后,分子对接研究表明，该化合物可以通过多种非共价相互作用很好地嵌入SDH的活性口袋，涉及SER39、ARG43和GLY46等残基。
