Fan Hailing, Chen Huiyin, Chen Quanjia, Pan Le, Jin Lu
College of Chemistry and Chemical Engineering, Xinjiang Agricultural University, Urumqi, China.
Engineering Research Centre of Cotton, Ministry of Education, College of Agriculture, Xinjiang Agricultural University, Urumqi, China.
Chem Biodivers. 2025 Aug;22(8):e202500386. doi: 10.1002/cbdv.202500386. Epub 2025 Apr 1.
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.
开发新型杀菌剂对于保护作物和确保农业可持续发展至关重要。共合成了33种5H-色烯并[4,3-b]吡啶-5-酮衍生物，并评估了这些衍生物对四种致病真菌（链格孢、茄链格孢、灰葡萄孢和尖孢镰刀菌）的抗真菌活性。结构-性质关系表明，在羟基位置引入侧链基团对抗真菌活性起显著作用，抑制率提高了3至4倍。结果表明，与阳性对照蛇床子素和嘧菌酯相比，化合物1i表现出优异的抗真菌活性。在浓度为100μg/mL时，1i对链格孢的抑制率为68.90%，半数有效浓度值为15.72μg/mL。此外，发现1i在400μg/mL时对梨上链格孢的体内抑制率在7天后保持在56.4%，比阳性对照（嘧菌酯为37.3%，蛇床子素为42.3%）更有效。基于同源建模的分子对接显示，化合物1i位于由琥珀酸脱氢酶（SDH）的Pro-380、Thr-307、Leu-305、Gln-103、Gly-104、Thr-266、His-406、Ala-101、Ala-102、Arg-451、His-98、Leu-457和Thr-99等氨基酸残基构成的口袋中，结合能为-7.16 kcal/mol。表明化合物1i可被视为SDH的潜在抑制剂以发挥抗真菌活性。
