title: Methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis and Enterococcus faecium active dimeric isobutyrylphloroglucinol from Ivesia gordonii.
abstract: Bioassay-guided fractionation of the chloroform soluble fraction of stem, leaf, and flower extracts of the American plant Ivesia gordonii led to the isolation of a new dimeric acylphloroglucinol, 3,3'-diisobutyryl-2,6'-dimethoxy-4,6,2',4'-tetrahydroxy-5,5'dimethyldiphenyl methane (1), to which we have assigned the trivial name ofivesinol (1), together with a known monomeric acylphloroglucinol, 1,5-dihydroxy-2-(2'-methylpropionyl)-3-methoxy-6-methylbenzene (2). The structures of the isolated compounds were characterized using 1D- and 2D- NMR spectroscopy, including COSY, HMQC, HMBC, and ROESYexperiments, as well as mass spectrometry. Ivesinol (1) showed potent activity against Staphylococcus aureus (SA) and methicillin-resistant S. aureus (MRSA) with IC50/MIC/MBC values of 0.10/1.25/>20 microg/mL and 0.05/0.31/>20 microg/mL, respectively (vs. IC50/MIC/MBC 0.13/0.5/1.0 microg/mL and 0.13/0.5/1.0 microg/mL of ciprofloxacin), while the corresponding monomer 2 was found to be less active. Compound 1 also demonstrated strong activity against vancomycin-resistant Enterococcus faecium (VRE) with IC50/MlC/MBC values of 0.22/1.25/>20 microg/mL, whereas the reference standard ciprofloxacin was found to be inactive against this strain. In addition, compound 2 showed moderate activity against two species of Candida and Cryptococcus neoformans, while 1 was inactive against these fungi. In order to evaluate the influence of the acyl group(s) in phloroglucinol (3) as a ligand, the mono- (4) and diacetylphloroglucinol (5) were prepared from 3, and evaluated for their in vitro SA, MRSA, and VRE activities; 2,4-diacetylphloroglucinol (5) showed potent activity, like 1, against SA, MRSA, and VRE (ATCC 700221) with IC50/MIC values of 0.3/2.5, 0.23/2.5, and 0.86/2.5 microg/mL, respectively, while 4 was inactive.
authors.forename: Marwa H
authors.initials: MH
authors.lastname: Ahmed
authors.forename: Mohamed Ali
authors.initials: MA
authors.lastname: Ibrahim
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Farouk R
authors.initials: FR
authors.lastname: Melek
authors.forename: Seham S
authors.initials: SS
authors.lastname: El-Hawary
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Jacob
authors.forename: Ilias
authors.initials: I
authors.lastname: Muhammad
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D013293:Enterococcus faecalis / Q000187:drug effects*; D016984:Enterococcus faecium / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D027824:Rosaceae / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014640:Vancomycin / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D010696:Phloroglucinol