BACKGROUND: To obtain new environmentally friendly fungicides, we used the natural product pimprinine as the lead compound, and designed and synthesized two series of ring-opening derivatives of pimprinine containing amide/thioamide. We then studied their antifungal activity against six common plant pathogenic fungi in vitro.RESULTS: Most of the target compounds have good antifungal activity against six important plant pathogenic fungi in vitro. At a concentration of 50 ∼g ml −1 , compound 3o showed prominent antifungal effects on Alternaria solani and Rhioctornia solani, with inhibition rates of 91.8% and 97.4%, and a 50% effective concentration (EC 50 ) of 6.2255 and 0.6969 ∼g ml −1 respectively. The EC 50 of compound 3o against Alternaria solani was significantly lower than that of boscalid (13.0380 ∼g ml −1 ) and flutriafol (11.9057 ∼g ml −1 ). In addition, compound 3o had good antifungal activity against Sclerotinia sclerotiorum, cucumber powdery mildew, cucumber Botrytis cinerea and Phytophthora capsici in vivo; the antifungal activity of compound 3o against cucumber Botrytis cinerea is 91.7%. At the same time, docking results for highly active compound 3o with the presumed target succinate dehydrogenase and the molecular docking prediction scores of all compounds further indicate its possible antifungal activity mechanism.CONCLUSION: The designed and optimized derivative 3o of ring-opening pimprinine has good antifungal activity and can be used as a new antifungal drug for further research.

Pimprinine and streptochlorin are indole alkaloids derived from marine or soil microorganisms. In our previous study, they were promising lead compounds due to their potent bioactivity in preventing many phytopathogens, but further structural modifications are required to improve their antifungal activity. In this study, pimprinine and streptochlorin were used as parent structures with the combination strategy of their structural features. Three series of target compounds were designed and synthesized. Subsequent evaluation for antifungal activity against six common phytopathogenic fungi showed that some of thee compounds possessed excellent effects, and this is highlighted by compounds 4a and 5a, displaying 99.9% growth inhibition against Gibberella zeae and Alternaria Leaf Spot under 50 μg/mL, respectively. EC50 values indicated that compounds 4a, 5a, 8c, and 8d were even more active than Azoxystrobin and Boscalid. SAR analysis revealed the relationship between 5-(3′-indolyl)oxazole scaffold and antifungal activity, which provides useful insight into the development of new target molecules. Molecular docking models indicate that compound 4a binds with leucyl-tRNA synthetase in a similar mode as AN2690, offering a perspective on the mode of action for the study of its antifungal activity. These results suggest that compounds 4a and 5a could be regarded as novel and promising antifungal agents against phytopathogens due to their valuable potency.