Design, synthesis and antifungal activity evaluation of chromeno[4,3-b]pyridin-5-one derivatives

Based on the scaffold of chromeno[4,3-b]pyridin-5-one found in a natural product (polynemoraline C), a series of 45 novel derivatives have been designed and investigated for their fungicide activity and corresponding synthesis methods. All compounds were characterized by 1H NMR and 13C NMR, and some by HR-MS. The antifungal activities were screened at 100 µg/mL against Alternaria alternata, Alternaria solani, Botrytis cinerea, Fusarium oxysporum. The results showed that most of the compounds were more effective against Alternaria alternata and Alternaria solani than Botrytis cinerea and Fusarium oxysporum. Some compounds were better than the positive controls. Among the synthesized derivatives, compound 1b showed remarkable activity against Alternaria alternata and Alternaria solani. The inhibition rate of compound 1b against Alternaria alternata at 100 µg/mL reached 62.09 %, which was higher than those of the positive controls, chlorothaloni (38.81 %) and azoxystrobin (50.06 %), while it was 54.61 % against Alternaria solani, which was higher than that of chlorothaloni (44.67 %) and almost equal to azoxystrobin (57.43 %). The EC50 values of compound 1b for Alternaria alternata and Alternaria solani were 62.73 and 65.95 μg/mL respectively. Structurally, the side chains of specific ester groups attached to the C-7 site of some compounds exhibit excellent inhibitory activity. The structure-activity relationship suggested that the length of the four carbon atoms in the side chain had significant effects on the antifungal activity. Our results revealed that a new series of chromeno[4,3-b]pyridin-5-one showed potential as an effective antifungal scaffold, and also provided a possibility for the structure design optimization, synthesis and development of a novel fungicide based on natural products.