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 of ivesinol (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 ROESY experiments, 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 μg/mL and 0.05/0.31/>20 μg/mL, respectively (vs. IC₅₀/MIC/MBC 0.13/0.5/1.0 μg/mL and 0.13/0.5/1.0 μg/mL of ciprofloxacin), while the corresponding monomer 2 was found to be less active. Compound 1 also demonstrated strong activity against vancomycin-resistant Enteococcus faecium (VRE) with IC₅₀/MIC/MBC values of 0.22/1.25/>20 μg/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 μg/mL, respectively, while 4 was inactive.