3D-QSAR-Directed Synthesis of Halogenated Coumarin-3-Hydrazide Derivatives: Unveiling Their Potential as SDHI Antifungal Agents

• DOI: 10.1021/acs.jafc.4c00200
• Publication Date: 2024-05-16T11:04:55Z
• Authors: Peng Dai; Zihua Ma; Xiang Yu; Wei Chen; Peng Teng; Yufei Li; Zhaojun Xu; Qing Xia; Zewen Liu; Weihua Zhang
• Keywords: Succinate Dehydrogenase; Fungal Proteins; Molecular Docking Simulation; Hydrazines; Antifungal Agents; Molecular Structure; Halogenation; Coumarins; Colletotrichum; Quantitative Structure-Activity Relationship; Enzyme Inhibitors; Fungicides, Industrial; Rhizoctonia

The pursuit of new succinate dehydrogenase (SDH) inhibitors is a leading edge in fungicide research and development. use 3D quantitative structure–activity relationship (3D-QSAR) models significantly enhances the development compounds with potent antifungal properties. In this study, we leveraged natural product coumarin as molecular scaffold to synthesize 74 novel 3-coumarin hydrazide derivatives. Notably, 4ap (0.28 μg/mL), 6ae (0.32 6ah (0.48 μg/mL) exhibited exceptional vitro effectiveness against Rhizoctonia solani, outperforming commonly used boscalid (0.52 μg/mL). Furthermore, 4ak (0.88 (0.61 (0.65 6ak (1.11 showed significant activity Colletotrichum orbiculare, surpassing both SDHI (43.45 broad-spectrum carbendazim (2.15 Molecular docking studies SDH enzyme assays indicate that compound 4ah may serve promising fungicide. Our ongoing aims refine 3D-QSAR model further, enhance design, conduct additional bioactivity assays.