title: Design, synthesis, and biological evaluation of chrysin derivatives as potential FabH inhibitors.
abstract: New series of chrysin derivatives (4a-4t) were designed and synthesized by introducing different substituted piperazines at C-7 position. Their inhibitory effects on FabH were evaluated using two Gram-negative bacterial strains, Escherichia coli and Pseudomonas aeruginosa, and two Gram-positive bacterial strains, Bacillus subtilis and Staphylococcus aureus. To our delight, most of these compounds exhibited a dramatic increase in inhibitory potency, compared with the control positive drugs. Among them, compound 4s exhibited the most potent inhibitory activity with IC50values of 5.78 ± 0.24 μm inhibiting E. coli FabH and potent antibacterial activity against S. aureus and E. coli with MIC of 1.25 ± 0.01, 1.15 ± 0.12 μg/mL, respectively, comparing to the control positive drugs penicillin G (7.56 ± 0.30 μm). Docking simulation was performed to position compound 4s into the FabH active site, and the result showed that compound 4s could bind well with the FabH as potent FabH inhibitor.
authors.affiliation: School of Life and Food Engineering, Suzhou University, Suzhou Anhui, People's Republic of China.|State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, People's Republic of China.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Li
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, People's Republic of China.
authors.forename: Zhong-Chang
authors.initials: ZC
authors.lastname: Wang
authors.affiliation: School of Life and Food Engineering, Suzhou University, Suzhou Anhui, People's Republic of China.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, People's Republic of China.
authors.forename: Xiao-Qiang
authors.initials: XQ
authors.lastname: Yan
authors.affiliation: Neonatal Medical Center, Nanjing Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors.forename: Ya-Dong
authors.initials: YD
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, People's Republic of China.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; D000123:Acetyltransferases / Q000037:antagonists & inhibitors*; D018360:Crystallography, X-Ray; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors*; D054889:Fatty Acid Synthase, Type II / Q000037:antagonists & inhibitors; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation
chemical_list: D029968:Escherichia coli Proteins; D005419:Flavonoids; C043561:chrysin; D000123:Acetyltransferases; C557158:fabH protein, E coli; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; D054889:Fatty Acid Synthase, Type II
keywords: FabH; antibacterial activities; chrysin derivatives; docking; synthesis