Combretastatin A-4 and Derivatives: Potential Fungicides Targeting Fungal Tubulin

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• 作者：Zhong-lin Ma ; Xiao-jing Yan ; Lei Zhao ; Jiu-jiu Zhou ; Wan Pang ; Zhen-peng Kai ; Fan-hong Wu
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2016
• 出版时间：February 3, 2016
• 年：2016
• 卷：64
• 期：4
• 页码：746-751
• 全文大小：317K
• ISSN：1520-5118

文摘

Combretastatin A-4, first isolated from the African willow tree Combretum caffrum, is a tubulin polymerization inhibitor in medicine. It was first postulated as a potential fungicide targeting fungal tubulin for plant disease control in this study. Combretastatin A-4 and its derivatives were synthesized and tested against Rhizoctonia solani and Pyricularia oryzae. Several compounds have EC₅₀ values similar to or better than that of isoprothiolane, which is widely used for rice disease control. Structure–activity relationship study indicated the the cis configuration and hydroxyl group in combretastatin A-4 are crucial to the antifungal effect. Molecular modeling indicated the binding sites of combretastatin A-4 and carbendazim on fungal tubulin are totally different. The bioactivity of combretastatin A-4 and its derivatives against carbendazim-resistant strains was demonstrated in this study. The results provide a new approach for fungicide discovery and fungicide resistance management.