title: Combretastatin A-4 and Derivatives: Potential Fungicides Targeting Fungal Tubulin.
abstract: 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.
authors.affiliation: School of Chemical and Environmental Engineering, Shanghai Institute of Technology , Shanghai 201418, People's Republic of China.
authors.forename: Zhong-lin
authors.initials: ZL
authors.lastname: Ma
authors.affiliation: Institute of Plant Protection, China Academy of Agricultural Sciences , Beijing 100193, People's Republic of China.
authors.forename: Xiao-jing
authors.initials: XJ
authors.lastname: Yan
authors.affiliation: School of Chemical and Environmental Engineering, Shanghai Institute of Technology , Shanghai 201418, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.affiliation: School of Chemical and Environmental Engineering, Shanghai Institute of Technology , Shanghai 201418, People's Republic of China.
authors.forename: Jiu-jiu
authors.initials: JJ
authors.lastname: Zhou
authors.affiliation: School of Chemical and Environmental Engineering, Shanghai Institute of Technology , Shanghai 201418, People's Republic of China.
authors.forename: Wan
authors.initials: W
authors.lastname: Pang
authors.affiliation: School of Chemical and Environmental Engineering, Shanghai Institute of Technology , Shanghai 201418, People's Republic of China.
authors.forename: Zhen-peng
authors.initials: ZP
authors.lastname: Kai
authors.affiliation: School of Chemical and Environmental Engineering, Shanghai Institute of Technology , Shanghai 201418, People's Republic of China.|Shanghai Engineering Research Center of Pharmaceutical Progress , Shanghai 201203, People's Republic of China.
authors.forename: Fan-hong
authors.initials: FH
authors.lastname: Wu
mesh_terms: D001203:Ascomycota / Q000187:drug effects / Q000378:metabolism; D029765:Combretum / Q000737:chemistry*; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D005659:Fungicides, Industrial / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010935:Plant Diseases / Q000382:microbiology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012232:Rhizoctonia / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D005656:Fungal Proteins; D005659:Fungicides, Industrial; D010936:Plant Extracts; D014404:Tubulin; D050257:Tubulin Modulators
keywords: combretastatin; fungicide; molecular modeling; resistance; tubulin