Phytochemical and Antibacterial Studies on the Genius Hypericum

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Phytochemical and antibacterial studies on the genus Hypericum, with synthesis of antibacterial acylphloroglucinol derivatives

This thesis is part of an ongoing project to characterize the antibacterial constituents of the genus Hypericum and to investigate their antibacterial activity. Bioassay-guided fractionation using various chromatography techniques was carried out on six plants in this study. Fifteen natural products were isolated. Their structures were characterized by extensive 1- and 2-dimentional NMR experiments. A panel of Staphylococcus aureus strains was used in minimum inhibitory concentration (MIC) assays to evaluate the antibacterial properties of the plant extracts and isolated compounds. 2,5-dihydroxy-1-methoxyxanthone was isolated from the dichloromethane (DCM) extract of H. forrestii. Fractionation of the DCM extract of H. moserianum and H. revolutum ssp. revolutum yielded 1,7-dihydroxyxanthone and the new 3-hydroxy-1,4,7-trimethoxydibenzofuran respectively. All three compounds were active against various S. aureus strains with MIC values ranging from 128 to 256 μg/ml. Stigmasterol was isolated from the hexane extract of H. beanii. Fractionation of the DCM extract of this plant led to the isolation of 1,7-dihydroxyxanthone and a mixture of two new acylphloroglucinols. (+)-catechin and (-)-shikimic acid were isolated from the methanol extract. The acylphloroglucinol mixture showed MIC values of 16-32 μg/ml. Stigmasterol, (+)-catechin and (-)-shikimic acid were inactive at 512 μg/ml. Fractionation of the hexane extract of H. olympicum L. cf. uniflorum yielded β-sitosterol (inactive at 512 μg/ml) and a new acylphloroglucinol (WS-09; MIC = 0.5 to 1 μg/ml). Fractionation of the DCM extract of this plant yielded four other closely related acylphloroglucinols, with MIC values ranging from 64 to 128 μg/ml. A new pyranone and lupeol were isolated from the hexane and DCM extracts of H. choisianum respectively. Both compounds were inactive at 512 μg/ml. Due to the excellent activity of WS-09, a four-step synthesis method was designed and patented. Twenty-five compounds were synthesized and the structure-activity relationship of various acylphloroglucinol derivatives was investigated

Dibenzofuran and pyranone metabolites from Hypericum revolutum ssp. revolutum and Hypericum choisianum

In a project to isolate and characterise anti-staphylococcal compounds from members of the genus Hypericum, a dibenzofuran and a pyranone were isolated from the dichloromethane and hexane extracts of Hypericum revolutum ssp. revolutum Vahl (Guttiferae) and Hypericum choisianum Wall. ex. N. Robson (Guttiferae), respectively. The structures of these compounds were elucidated by 1- and 2D-NMR spectroscopy and mass spectrometry as 3-hydroxy-1,4,7-trimethoxydibenzofuran (1) and 4-(3-O-3″)-3″-methylbutenyl-6-phenyl-pyran-2-one (2). The metabolites were evaluated against a panel of multidrug-resistant strains of Staphylococcus aureus. Compound 1 exhibited a minimum inhibitory concentration (MIC) of 256 μg/ml, whereas compound 2 was inactive at a concentration of 512 μg/ml

Anti-staphylococcal acylphloroglucinols from Hypericum beanii

As part of an ongoing project to investigate the anti-staphylococcal properties of the Hypericum genus, an acylphloroglucinol, 1,5-dihydroxy-2-(2′-methylpropionyl)-3-methoxy-6-methylbenzene (1), was isolated from the dichloromethane extract of the aerial parts of H. beanii (Guttiferae), together with a minor related acylphloroglucinol 1,5-dihydroxy-2-(2′-methylbutanoyl)-3-methoxy-6-methylbenzene (2) as a mixture in a 5:2 ratio. The known compounds 1,7-dihydroxyxanthone (3), stigmasterol, catechin and shikimic acid were also isolated from this plant. The structures of the compounds were characterized by extensive 1- and 2D NMR spectroscopy and mass spectrometry. The minimum inhibitory concentration (MIC) values the acylphloroglucinol mixture and (3) against a panel of multidrug-resistant strains of Staphylococcus aureus ranged from 16–32 μg/ml to 128–256 μg/ml, respectively

Polyisoprenylated Benzoylphloroglucinol Derivatives from Hypericum sampsonii

Bioassay-directed fractionation using multidrug-resistant (MDR) Staphylococcus aureus resulted in the isolation of four new polyprenylated benzophloroglucinol derivatives, sampsoniones N–Q (1–4), and four known compounds, 7-epiclusianone (5) and sampsoniones B, L, and R, from the roots of Hypericum sampsonii. The structures of these compounds were established by analysis of spectroscopic data, and the structures of 4 and 5 were determined by single-crystal X-ray diffraction crystallography. In the bioassay, 7-epiclusianone (5) showed promising activity with a minimum inhibitory concentration (MIC) of 7.3 µM against the NorA overexpressing MDR S. aureus strain SA-1199B; the positive control antibiotic norfloxacin showed activity at MIC 100 µM

Prenylated benzophenone peroxide derivatives from Hypericum sampsonii

Two new prenylated benzophenone peroxide derivatives, peroxysampsones A and B (1 and 2, resp.), together with a known compound, plukenetione C (3), were isolated from the roots of the Chinese medicinal plant Hypericum sampsonii, and their structures were elucidated by detailed spectral analysis. These compounds are the unusual peroxides of polyprenylated benzophenone derivatives, containing the unique caged moiety of 4,5-dioxatetracyclo[9.3.1.19,13.0 1,7]hexadecane-12,14,15-trione. In the biological test, peroxysampsone A (1) showed comparable activity with norfloxacin against a NorA over-expressing multidrug-resistant (MDR) strain of Staphylococcus aureus SA-1199B

A Naturally Occurring Inhibitory Agent from Hypericum sampsonii. with Activity Against Multidrug-Resistant Staphylococcus aureus .

Bioassay-directed fractionation employing a multidrug-resistant (MDR) strain of Staphylococcus aureus. resulted in the isolation of an antibacterial prenyl substituted xanthone derivative (1) named hyperixanthone A from the root of Hypericum sampsonii. Hance (Hyperiaceae). Compound 1 showed promising inhibitory activity against the norfloxacin-resistant S. aureus. strain SA-1199B at a minimum inhibitory concentration (MIC) of 2 μ g/mL (4.3 μ M), wheres the positive standard antibacterial drug norfloxacin showed an MIC of 32 μ g/mL (100 μ M). This strain overexpresses the NorA multidrug efflux transporter, the major characterized drug pump in Staphylococcus aureus.. The activity of this compound against an effluxing strain of S. aureus. is reported here for the first time. Compound 1, together with 1,7-dihydroxyxanthone (2) and 2-hydroxyxanthone (3), were obtained by silica gel column chromatography, and their structures were determined by means of extensive NMR and MS spectra