Design, Synthesis, Biological Evaluation, and Molecular Modeling of Novel 4H-Chromene Analogs as Potential Succinate Dehydrogenase Inhibitors.

Abstract

Thirty-one new 4H-chromene derivatives were designed and synthesized. Their structures were identified with IR, 1H NMR, 13C NMR, and HRMS. The crystal structure of compound 2a was determined by single-crystal X-ray diffraction. Their antifungal activities were evaluated against Pyricularia oryzae, Erysiphe graminis, Coniella diplodiella, Pseudoperonospora cubensis, and Sclerotinia sclerotiorum. These results demonstrated that most compounds exhibited remarkable inhibitory activities at 20 μg/mL. Compounds 4b and 4c displayed excellent antifungal activity against S. sclerotiorum and possessed better efficacy than fluopyram. At the same time, the inhibitory activity of the bioactive compounds was evaluated against succinate dehydrogenase (SDH). The results showed that these compounds possessed outstanding activity. Compounds 4b and 4c displayed better inhibitory activity than fluopyram. The molecular modeling results revealed that compound 4c had stronger affinity to SDH than fluopyram. It is the first time that the inhibitory activity of 4H-chromene analogs against SDH has been reported.