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, 1 H NMR, 13 C 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.

Lactobacillus plantarum ZLC‐18 fermentation improve tyrosinase inhibition activity and antioxidant capacity in soybean hulls

“…In the human body, tyrosinase overexpression can cause melanin deposition, resulting in freckles, age spots and chloasma. In fruits and vegetables, overexpression can cause browning, which greatly affects their flavour and taste and leads to a loss in nutrients (Lu, et al ., 2021). However, the existing chemosynthetic tyrosinase inhibitors have some problems, including a poor safety level, adverse reactions and a low efficiency (Obaid, et al ., 2021).…”

Design, Synthesis, and Fungicidal Evaluation of Novel 1,3-Benzodioxole-Pyrimidine Derivatives as Potential Succinate Dehydrogenase Inhibitors

“…A threedimensional (3D) structural model of SDH from S. sclerotiorum was constructed through homology modeling according to a previously reported method. 49 The energy-minimizing structure of 5c and boscalid were performed with Discovery Studio 2016. 50 Molecular docking for compound 5c and boscalid with SDH was also performed by the Discovery Studio 2016 program.…”

Comprehensive Overview of Carboxamide Derivatives as Succinate Dehydrogenase Inhibitors

“…Furthermore, compound 76 exhibited strong inhibitory effect against SDH enzymes with IC 50 values of 0.095 μg/mL, far superior to fluopyram (IC 50 = 0.356 μg/ mL). 112 The compound 77 bearing the 4,5-dihydro-1Hpyrazole scaffold exhibited significant antifungal activity against S. sclerotiorum with EC 50 value of 0.081 μg/mL, which was much better than that of control penthiopyrad (EC 50 = 0.25 μg/mL). Moreover, compound 77 displayed good inhibitory effect against SDH of S. sclerotiorum with IC 50 values of 0.104 μg/mL, comparable to that of penthiopyrad (IC 50 = 0.363 μg/ mL).…”

“…Compound 76 with a 4 H -chromene group displayed excellent antifungal activity against S. sclerotiorum with EC 50 value of 0.063 μg/mL, which was about 4-fold more potent than that of fluopyram (EC 50 = 0.244 μg/mL). Furthermore, compound 76 exhibited strong inhibitory effect against SDH enzymes with IC 50 values of 0.095 μg/mL, far superior to fluopyram (IC 50 = 0.356 μg/mL) . The compound 77 bearing the 4,5-dihydro-1 H -pyrazole scaffold exhibited significant antifungal activity against S. sclerotiorum with EC 50 value of 0.081 μg/mL, which was much better than that of control penthiopyrad (EC 50 = 0.25 μg/mL).…”