Synthesis of Novel\nChromene Derivatives Bearing Hydrazide/Thiazol/Oxazol/Oxime\nMoieties as Potential Antifungal Agents

Four series of novel hydrazide/thiazol/oxazol/oxime ester\nhybrids\nof chromene derivatives were designed and synthesized to explore natural-product-based\nfungicide candidates. Preliminary antifungal activity assay results\ndemonstrated that hydrazide-chromene and thiazol-chromene derivatives\nexhibited excellent and broad-spectrum inhibitory activity against\nten phytopathogenic fungi. Among them, six compounds <b>4b</b>, <b>4c</b>, <b>4d</b>, <b>4e</b>, <b>4h</b>, and <b>4l</b> displayed the most remarkable antifungal effects.\nNotably, compounds <b>4e</b> and <b>4l</b> showed comparable\nprotective and curative effects with chlorothalonil against potatoes\nand cherry tomatoes infected by Fusarium solani and Botrytis cinerea, respectively.\nMeanwhile, compound <b>4e</b> also exerted potential protective\nand curative effects against rice and pepper leaves infected by Pyricularia oryzae and Phytophthora\ncapsici, respectively. Additionally, a preliminary\nantifungal mechanism study revealed that compound <b>4e</b> could\nsignificantly inhibit the germination of spores and promote increased\nmycelium permeability and content leakage by disrupting the fungal\nmembrane structure. The in vitro cytotoxicity results indicated that\nalmost all of the hydrazide-chromene derivatives possessed relatively\nlow cytotoxicity. These findings provide the foundation for the application\nof chromene-based derivatives as novel fungicide candidates.