Indole/Tetrahydroquinoline as Renewable Natural Resource-Inspired Scaffolds in the Devising and Preparation of Potential Fungicide Candidates.

Abstract

As a continuous effort toward developing novel and highly efficient agrochemicals for integrated management of crop pathogens, two series of oxime ester derivatives from indole and tetrahydroquinoline natural scaffolds were prepared. Guided by the preliminary inhibition rates against ubiquitous and representative fungi, the antifungal profile of the target compounds against Valsa mali was intensively and extensively studied. The tetrahydroquinoline-based derivatives 12a-12r exerted a promising inhibition effect, especially against V. mali. The remarkable compounds 12p (R = 4-OCF3) and 12r (R = 4-OBn) with EC50 values of 0.81 and 0.47 μg/mL, respectively, have a far more prominent activity than commercial fungicide trifloxystrobin. The biochemistry and physiology responses of V. mali after treatment with target compound 12p was examined, and the fruit body production, hyphae morphology, and organelles were profoundly affected. Moreover, the curative effects of compound 12p on apple detached branches and leaves were 57.69 and 64.84% at 100 μg/mL, respectively, which were even superior to that of trifloxystrobin. Meanwhile, the three-dimensional quantitative structure-activity relationship model [comparative molecular field analysis (CoMFA): q2 = 0.823, r2 = 0.924, F = 189.781, and standard error of estimation (SEE) = 0.138 and comparative molecular similarity index analysis (CoMSIA): q2 = 0.795, r2 = 0.904, F = 145.644, and SEE = 0.156] indicated that the antifungal activity of target compounds was facilitated by crucial structural factors, which would render inspiration for further design and discovery of novel fungicidal candidates.