Natural Osthole-Based Ester Derivatives as Potential Fungicidal Agents: Design, Synthesis and Quantitative Structure-Activity Relationship (QSAR)

Abstract

Turning potential natural products into value-added fungicides is a bioactivity-guided mixed synthesis method. Thirty-two derivatives were designed and synthesized to improve the potential use of the osthole, a natural coumarin pharmacophore. Compound Os14 with 3-ClPh showed a high in vitro and in vivo antifungal activity than other derivatives. The preliminary structure-activity relationships (SARs) demonstrated that compounds with a short aliphatic chain or electron-withdrawing groups on phenyl ring would have more desirable potency. Meanwhile, the quantitative structure-activity relationship (QSAR) model (R-2 = 0.928, F = 83.54, S-2 = 0.0042) were performed using Gaussian and CODESSA software with optimal conformers and heuristic regression analysis, which revealed a correlation of antifungal activity and molecular structures. Thus, these results laid the foundation for further design of improved crop-protection agents based on osthole scaffold.