Antibacterial and Cytotoxic Activity of Prenylated Bicyclic Acylphloroglucinol Derivatives from Hypericum amblycalyx

Abstract

Two new bicyclic acylphloroglucinol derivatives, hypercalyxone A (1-[5,7-dihydroxy-2-methyl-3-(3-methyl-but-2-enyl)-2-(4-methyl-pent-3-enyl)-chroman-8-yl]-2-methyl-propan-1-one, 1) and B (1-[5,7-dihydroxy-2-methyl-3-(3-methyl-but-2-enyl)-2-(4-methyl-pent-3-enyl)-chroman-8-yl]-2-methyl-butan-1-one, 2), have been isolated from the petroleum ether extract of the aerial parts of Hypericum amblycalyx, together with two further compounds (1-[5,7-dihydroxy-2-methyl-2-(4-methyl-pent-3-enyl)-chroman-8-yl]-2-methyl-propan-1-one, 3 and 1-[5,7-dihydroxy-2-methyl-2-(4-methyl-pent-3-enyl)-chroman-8-yl]-2-methyl-butan-1-one, 4), which have been described only as semi-synthetic products. In addition, the known triterpene lup-20(29)-en-3-one was obtained. Structure elucidation was based on 1D and 2D NMR studies, as well as on data derived from mass spectrometry. The four acylphloroglucinol derivatives were evaluated for their cytotoxic and antibacterial activity. All compounds showed moderate cytotoxic activity against KB and Jurkat T cancer cells. Especially compounds 3 and 4 exhibited a strong antibacterial activity against different Gram-positive strains.

Bioactive acylphloroglucinols from Hypericum densiflorum

“…Phytochemical studies of St John's wort and other Hypericum species have resulted in the isolation of a wide range of natural products with anti-HIV, antiinflammatory, antitumor, antibacterial and antioxidant activities. These compounds include acylphloroglucinol derivatives, flavonoids and xanthones (Albert et al, 2002;Athanasas et al, 2004;Tanaka et al, 2005;Verotta, 2002;Winkelmann et al, 2003).…”

Inhibition of Bacterial Growth and Biofilm Production by Constituents from Hypericum spp.

“…Winkelmann et al . reported modest antistaphylococcal activity (32 µg/mL) for a related acylphloroglucinol lacking one of the additional isoprene units of 7 , further demonstrating the detrimental effects of the cyclization and/or increased lipophilicity (Winkelmann et al ., ).…”

“…The results of these studies add to growing knowledge of the antimicrobial properties of acylphloroglucinol metabolites. Other studies have reported acylphloroglucinol derivatives possessing antimicrobial activity against staphylococci (Ishiguro et al ., ; Schempp et al ., ; Winkelmann et al ., , ; Gibbons et al ., ; Pecchio et al ., ; Henry et al ., ). A study by Socolsky et al .…”

Bi-, Tri-, and Polycyclic Acylphloroglucinols from Hypericum empetrifolium

“…The signal patterns and shift values of the remaining carbon and proton signals were similar to those of the bicyclic compound 1-[5,7-dihydroxy-2-methyl-2-(4-methylpent-3-enyl)chroman-8-yl]-2-methylpropan-1-one (7) previously isolated from H. amblycalyx. 12 The main difference between the two compounds was an additional C-3−C-4 double bond evident from the resonances of two methine carbons (δ C 123.2, C-3; 116.8, C-4) rather than two methylene carbons and of the corresponding protons H-3 (δ H 5.41, d, J = 10.0 Hz) and H-4 (δ H 6.59, d, J = 10.0 Hz). Compound 1 was determined to be 1-[5,7-dihydroxy-2-methyl-2-(4-methylpent-3-enyl)chromen-8-yl]-2-methylpropan-1-one and given the trivial name empetrikarinen A.…”