Discovery of Natural Product-Based Fungicides (III): Semisynthesis and Biological Activity of N-Phenylpyrazole Sarisan Hybrids as Antifungal Agents.

Many phytopathogenic fungi can easily infect crops, resulting in crop yield reductions. In continuation of our effort to develop natural product (NP)-based antifungal agents, a series of N -phenylpyrazole sarisan hybrids 6a - v were prepared via I 2 -mediated oxidative cyclization, and their structures were determined by various spectral analyses including IR, 1 H NMR and ESI-MS. Among all N- phenylpyrazole sarisan hybrids, compounds 6a , 6b , 6e , 6i , 6j and 6r showed more potent antifungal activity against at lest two phytopathogenic fungi than the commercial fungicide hymexazol. In particular, compound 6a exhibited more broad-spectrum and promising antifungal activity against three phytopathogenic fungi ( V. mali , F. oxysporum f.sp.niveum , and F. graminearum ) with the EC 50 values of 18.5, 37.4 and 12.6 μg/mL, respectively. Moreover, the structure-activity relationships (SARs) were also observed. Additionally, compounds 6a and 6e also exhibited relative low toxicity on normal LO2 cells. This work indicates that these N -phenylpyrazole sarisan hybrids would shed light on developing novel NP-based antifungal agents.