Novel 5H-Chromeno[4,3-b]Pyridin-5-One Derivatives Against Phytopathogenic Fungi: Synthesis and Molecular Docking

The development of novel fungicides is imperative for the protection of crops and the assurance of sustainable agricultural development. A total of 33 5H-chromeno[4,3-b]pyridin-5-one derivatives have been synthesized, and the antifungal activities of these derivatives against four pathogenic fungi (Alternaria alternata, Alternaria solani, Botrytis cinerea, and Fusarium oxysporum) have been evaluated. The structure-property relationship indicated that the introduction of side-chain groups at the hydroxyl position played a significant role in the antifungal activity, with the inhibition rates increasing by 3-4 folds. The results demonstrate that compound 1i exhibits superior antifungal activity in comparison to the positive controls, osthole, and azoxystrobin. The inhibition rate of 1i against A. alternata was found to be 68.90% at a concentration of 100 µg/mL, with a median effective concentration value of 15.72 µg/mL. Additionally, the in vivo inhibition rate of 1i against A. alternata on pears was found to keep 56.4% at 400 µg/mL after 7 days, which is more effective than those of the positive controls (37.3% for azoxystrobin and 42.3% for osthole). Molecular docking based on homology modeling reveals that the compound 1i is placed in a pocket constructed from amino acid residues including Pro-380, Thr-307, Leu-305, Gln-103, Gly-104, Thr-266, His-406, Ala-101, Ala-102, Arg-451, His-98, Leu-457, and Thr-99 of succinic dehydrogenase (SDH) with the binding energy of -7.16 kcal/mol. It was suggested that the compound 1i can be considered a potential inhibitor of SDH to exhibit antifungal activity.