title: Synthesis, Biological Evaluation, and Molecular Modeling Studies of New Oxadiazole-Stilbene Hybrids against Phytopathogenic Fungi.
abstract: Natural stilbenes (especially resveratrol) play important roles in plant protection by acting as both constitutive and inducible defenses. However, their exogenous applications on crops as fungicidal agents are challenged by their oxidative degradation and limited availability. In this study, a new class of resveratrol-inspired oxadiazole-stilbene hybrids was synthesized via Wittig-Horner reaction. Bioassay results indicated that some of the compounds exhibited potent fungicidal activity against Botrytis cinerea in vitro. Among these stilbene hybrids, compounds 11 showed promising inhibitory activity with the EC50 value of 144.6 μg/mL, which was superior to that of resveratrol (315.6 μg/mL). Remarkably, the considerably abnormal mycelial morphology was observed in the presence of compound 11. The inhibitory profile was further proposed by homology modeling and molecular docking studies, which showed the possible interaction of resveratrol and oxadiazole-stilbene hybrids with the cytochrome P450-dependent sterol 14α-demethylase from B. cinerea (BcCYP51) for the first time. Taken together, these results would provide new insights into the fungicidal mechanism of stilbenes, as well as an important clue for biology-oriented synthesis of stilbene hybrids with improved bioactivity against plant pathogenic fungi in crop protection.
authors.affiliation: School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, Guangdong 510640, People's Republic of China.
authors.forename: Weilin
authors.initials: W
authors.lastname: Jian
authors.affiliation: School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, Guangdong 510640, People's Republic of China.
authors.forename: Daohang
authors.initials: D
authors.lastname: He
authors.affiliation: State Key Lab of Biocontrol, Sun Yat-sen University, Guangzhou, Guangdong 510006, People's Republic of China.
authors.forename: Shaoyun
authors.initials: S
authors.lastname: Song
mesh_terms: D020171:Botrytis / Q000187:drug effects* / Q000502:physiology; D005659:Fungicides, Industrial / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D050296:Microbial Viability / Q000187:drug effects; D062105:Molecular Docking Simulation; D025282:Mycelium / Q000187:drug effects / Q000502:physiology; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D058886:Sterol 14-Demethylase / Q000737:chemistry; D013267:Stilbenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D005659:Fungicides, Industrial; D010069:Oxadiazoles; D013267:Stilbenes; D058886:Sterol 14-Demethylase