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Design, synthesis, and biological evaluation of chrysin derivatives as potential FabH inhibitors
Author(s) -
Li HongXia,
Wang ZhongChang,
Qian YuMei,
Yan XiaoQiang,
Lu YaDong,
Zhu HaiLiang
Publication year - 2017
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12839
Subject(s) - chrysin , chemistry , combinatorial chemistry , computational biology , pharmacology , biochemistry , biology , flavonoid , antioxidant
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 IC 50 values of 5.78 ± 0.24 μ m 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 μ g/mL, respectively, comparing to the control positive drugs penicillin G (7.56 ± 0.30 μ m ). 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.