Design, synthesis and evaluation of 3-arylidene azetidin-2-ones as potential antifungal agents against Alternaria solani Sorauer

摘要

Graphical abstract Display Omitted Abstract A new concise and facile method was explored to synthesize a collection of new 3-arylidene azetidin-2-ones, which could be regarded as the derivatives of the hybrid scaffold of bioactive natural cinnamamide and heterocycle azetidi-2-one. The structures of the synthesized compounds were characterized by 1 H, 13 C NMR, and MS; and their antifungal activity were evaluated against Alternaria solani Sorauer. These antifungal data were subjected to a quantitative structure–activity relationship (QSAR) analysis using Codessa software on the basis of the results from B3LYP/6-31G(d,p) quantum calculations. The best regressive model revealed that potentially more active compounds should have low dipole moments and Q C-min (minimal net atomic charge for a C atom), and high Q O-max (maximal net atomic charge for an O atom) and Q N-min (minimal net atomic charge for an N atom). The most potent compound 7k could lead to intracellular accumulation of reactive oxygen species, dissipation of mitochondrial transmembrane potential, and an autophagy-like cell death process in A. solani Sorauer. Taken together, these results laid the foundation for further design of improved crop-protection agents based on this hybrid scaffold.