title: Synthesis and biological evaluation of novel inhibitors against 1,3,8-trihydroxynaphthalene reductase from Magnaporthe grisea.
abstract: 1,3,8-Trihydroxynaphthalene reductase (3HNR) is an essential enzymes that is involved in fungal melanin biosynthesis. Based on the structural informations of active site of 3HNR, a series of β-nitrostyrene compounds were rationally designed and synthesized. The enzymatic activities of these compounds showed that most of them exhibited high inhibitory activities (<5.0 μM) against 3HNR; compound 3-2 exhibit the highest inhibitory activity (IC50=0.29 μM). In particular, some of these compounds had moderate fungicidal activity against Magnaporthe grisea. Compound 3-4 showed high in vivo activities against M. grisea (EC50=9.5 ppm). Furthermore, compound 3-2 was selected as a representative molecule, and the probable binding mode of this compound and the surrounding residues in the active site of 3HNR was elucidated by using molecular dock. The positive results suggest that β-nitrostyrene derivatives are most likely to be promising leads toward the discovery of novel agent of rice blast.
authors: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, PR China; Ocean College, Qinzhou University, Qinzhou 535099, Guangxi, PR China.
authors: Haifeng
authors: H
authors: Chen
authors: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, PR China.
authors: Xinya
authors: X
authors: Han
authors: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, PR China.
authors: Nian
authors: N
authors: Qin
authors: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, PR China.
authors: Lin
authors: L
authors: Wei
authors: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, PR China.
authors: Yue
authors: Y
authors: Yang
authors: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, PR China.
authors: Li
authors: L
authors: Rao
authors: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, PR China.
authors: Bo
authors: B
authors: Chi
authors: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, PR China.
authors: Lingling
authors: L
authors: Feng
authors: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, PR China. Electronic address: renyl@mail.ccnu.edu.cn.
authors: Yanliang
authors: Y
authors: Ren
authors: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, PR China. Electronic address: jianwan@mail.ccnu.edu.cn.
authors: Jian
authors: J
authors: Wan
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020082:Magnaporthe / Q000187:drug effects* / Q000201:enzymology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013343:Styrenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D013343:Styrenes; C011955:beta-nitrostyrene; C086024:tetrahydroxynaphthalene reductase; D044925:Oxidoreductases Acting on CH-CH Group Donors
keywords: 1,3,8-Trihydroxynaphthalene reductase; Magnaporthe grisea; Novel inhibitors