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, leave, 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 spectrometery. 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 0.133/0.5/1.0 µg/mL and 0.128/0.5/1.0 µg/mL of ciprofloxacin), while the corresponding monomer 2 was found to be less active. Compound 1 also demonstrated strong activity against vancomycin-resistant Enterococcus faecium (VRE) with IC50/MIC/MBC values 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 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, where 2,4-diacetylphloroglucinol (5) showed potent activity, like 1, against SA, MRSA, and VRE (ATCC 700221) with IC50/ MIC values of 0.27/2.5 µg/mL, 0.23/2.5 µg/mL, and 0.86/2.5 µg/mL, respectively, while 4 was inactive.

Anti-Vancomycin-resistant Enterococcus faecium and E. faecalis Activities of (-)-Gossypol and Derivatives from Thespesia garckeana

“…However, mono-methoxylation substantially improved the antimicrobial selectivity of these compounds against C. glabrata, as exhibited by 2, which showed the highest antifungal activity. The antibacterial activities tend to be attributed to the hydrophilicity of gossypol (1) and derivatives (2,3), while the antifungal activities require some degree of lipophilicity, as observed in 2, which is in agreement with previous studies [29,30]. This appears to be the first report of (-)-gossypol (1) from the genus Thespesia.…”

“…The use of antibiotics inevitably leads to the emergence and rapid spread of multi-drug resistance in microbes. These strains that are resistant to almost all current antibiotic agents of choice compromise the treatment of bacterial, viral, fungal and parasitic infections posing potential threats to human health [1][2][3]. This phenomenon is exemplified by vancomycin-resistant Enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) strains which have developed resistance to most first-line antibiotics and currently there are very few antibiotics that can be used to combat infections caused by these microbes [2,3].…”

“…Bacteria of the genus Enterococcus are considered part of the normal flora of the gastrointestinal and genitourinary tracts of humans, and have emerged as one of the most important nosocomial pathogens, causing 12% of all hospital acquired infections [4]. E. faecalis and E. faecium are responsible for the majority of human enterococcal infections [3,5]. Colonization and infection by vancomycin-resistant Enterococci are associated with multidrug resistance and up to 75% mortality rate of those infected [6].…”

“…These strains that are resistant to almost all current antibiotic agents of choice compromise the treatment of bacterial, viral, fungal and parasitic infections posing potential threats to human health [1][2][3]. This phenomenon is exemplified by vancomycin-resistant Enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA) strains which have developed resistance to most first-line antibiotics and currently there are very few antibiotics that can be used to combat infections caused by these microbes [2,3]. Bacteria of the genus Enterococcus are considered part of the normal flora of the gastrointestinal and genitourinary tracts of humans, and have emerged as one of the most important nosocomial pathogens, causing 12% of all hospital acquired infections [4].…”

Saturated Fatty Acid-Based In Situ Forming Matrices for Localized Antimicrobial Delivery

“…[ 28 ]. The half maximal inhibitory concentration (IC 50 )/minimum inhibition concentration(MIC) of vancomycin HCl against S. aureus , MRSA, and E. faecalis were 0.37/0.625, 0.67/0.125, and 0.73/1.25 µg/mL, respectively [ 29 ]. While the MIC values of vancomycin HCl against beta-hemolytic streptococci, which include S. pyogenes , S. agalactiae , S. dysgalactiae , S. anginosus group, Group C streptococci, and Group G streptococci, were in the range of ≤0.015 to 1 µg/mL [ 30 ].…”