title: 18β-Glycyrrhetinic Acid Derivatives Possessing a Trihydroxylated A Ring Are Potent Gram-Positive Antibacterial Agents.
abstract: The oleanane-type triterpene 18β-glycyrrhetinic acid (1) was modified chemically through the introduction of a trihydroxylated A ring and an ester moiety at C-20 to enhance its antibacterial activity. Compounds 22, 23, 25, 28, 29, 31, and 32 showed more potent inhibitory activity against Streptomyces scabies than the positive control, streptomycin. Additionally, the inhibitory activity of the most potent compound, 29, against Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus was greater than that of the positive controls. The antibacterial mode of action of the active derivatives involved the regulation of the expression of genes associated with peptidoglycans, the respiratory metabolism, and the inherent virulence factors found in bacteria, as determined through a quantitative real-time reverse transcriptase PCR assay.
authors.affiliation: Ministry of Education Key Laboratory of Green Pesticide and Ago-Bioengineering, Center for Research and Development of Fine Chemicals of Guizhou University , Guiyang 550025, People's Republic of China.|The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences , Guiyang 550002, People's Republic of China.
authors.forename: Li-Rong
authors.initials: LR
authors.lastname: Huang
authors.affiliation: Ministry of Education Key Laboratory of Green Pesticide and Ago-Bioengineering, Center for Research and Development of Fine Chemicals of Guizhou University , Guiyang 550025, People's Republic of China.|The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences , Guiyang 550002, People's Republic of China.
authors.forename: Xiao-Jiang
authors.initials: XJ
authors.lastname: Hao
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences , Guiyang 550002, People's Republic of China.
authors.forename: Qi-Ji
authors.initials: QJ
authors.lastname: Li
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences , Guiyang 550002, People's Republic of China.
authors.forename: Dao-Ping
authors.initials: DP
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences , Guiyang 550002, People's Republic of China.
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Zhang
authors.affiliation: The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences , Guiyang 550002, People's Republic of China.
authors.forename: Heng
authors.initials: H
authors.lastname: Luo
authors.affiliation: Ministry of Education Key Laboratory of Green Pesticide and Ago-Bioengineering, Center for Research and Development of Fine Chemicals of Guizhou University , Guiyang 550025, People's Republic of China.|The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences , Guiyang 550002, People's Republic of China.
authors.forename: Xiao-Sheng
authors.initials: XS
authors.lastname: Yang
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006035:Glycyrrhiza / Q000737:chemistry; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D060888:Real-Time Polymerase Chain Reaction; D013302:Streptomyces / Q000187:drug effects; D013307:Streptomycin / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; C119129:18alpha-glycyrrhetinic acid; D014640:Vancomycin; D000667:Ampicillin; D006034:Glycyrrhetinic Acid; D013307:Streptomycin