Design, synthesis, antifungal activity, and 3D-QSAR of coumarin derivatives

Abstract

In our research, a series of 8-substituted coumarin derivatives were synthesized, and their structures were confirmed by FT-IR, ¹H-NMR, and MS (or HRMS). In activity screening, the synthesized compounds exhibited potent antifungal activity against 4 phytopathogenic fungi: <i>Botrytis cinerea</i>, <i>Colletotrichum gloeosporioides</i>, <i>Fusarium oxysporum</i>, and <i>Valsa mali</i>. Notably, 8-chloro coumarin and ethyl 8-chloro-coumarin<b>-</b>3-carboxylate showed the strongest fungus inhibition with EC₅₀ of 0.085 and 0.078 mmol/L against <i>V. mali</i>. Furthermore, 3D-QSAR models (CoMFA and CoMSIA) of the title compounds against <i>V. mali</i> were established on the basis of their antifungal activities. The results indicated that the appropriate small, hydrophilic and electron-withdrawing groups on coumarin's C-3 and C-8, respectively, could enhance the antifungal activity. The information obtained will be very helpful for designing new derivatives with high antifungal activities.