QSAR studies of phenylhydrazine-substituted tetronic acid derivatives based on the 1 H NMR and 13 C NMR chemical shifts

Abstract

The quantitative structure-activity relationship models of 40 phenylhydrazine-substituted tetronic acid derivatives were established between the ¹ H nuclear magnetic resonance (NMR) and ¹³ C NMR chemical shifts and the antifungal activity against Fusarium graminearum, Botrytis cinerea, Rhizoctonia cerealis, and Colletotrichum capsici. The models were validated by R, R² , R_A² , variance inflation factor, F, and P values testing and residual analysis. It was concluded from the models that the ¹³ C NMR chemical shifts of C8, C10, C7, and the ¹ H NMR chemical shifts of Ha contributed positively to the activity against Fusarium graminearum, Botrytis cinerea, Colletotrichum capsici, and Rhizoctonia cerealis, respectively. The models indicated that decreasing the election cloud density of specific nucleuses in compounds, for example, by the substituting of electron withdrawing groups, would improve the antifungal activity. These models demonstrated the practical application meaning of chemical shifts in the quantitative structure-activity relationship study. Furthermore, a practical guide was provided for further structural optimization of the antifungal phenylhydrazine-substituted tetronic acid derivatives based on the ¹ H NMR and ¹³ C NMR chemical shifts.

Keywords: 13C NMR; 1H NMR; QSAR; antifungal activity; chemical shift; tetronic acid.