Elsevier

Phytochemistry

Volume 89, May 2013, Pages 104-113
Phytochemistry

Minor C-geranylated flavanones from Paulownia tomentosa fruits with MRSA antibacterial activity

https://doi.org/10.1016/j.phytochem.2013.01.002Get rights and content

Abstract

Exhaustive chromatographic separation of the chloroform portion of the ethanolic extract obtained from Paulownia tomentosa (Thunb). Steud. (Paulowniaceae) fruits has led to isolation of ten C-6 geranylated flavanones tomentodiplacone C–I and mimulone C–E, featured by 3′-methoxy and 4′-hydroxy or 4′-hydroxy substitution of the B-ring of the flavonoid, respectively. The structures of these compounds were determined by using mass spectrometry (including HRMS) and 1D and 2D NMR spectroscopy. The absolute configurations of the compounds at C-2 were determined using circular dichroism. The obtained compounds showed the presence of a geranyl moiety functionalized by a carbonyl, hydroxyl or methoxyl group, or by formation of tetrahydrofuran or fused-pyrane ring, respectively. All of the flavanones described were isolated for the first time from a natural source. The antibacterial activities of selected compounds isolated along with the previously isolated geranylated flavanones were evaluated against a common panel of microbes and MRSA strains. The selected isolated compounds were tested for their ability to affect eukaryotic translation initiation via dual-luciferase reporter assay (firefly and renilla).

Graphical abstract

Paulownia tomentosa (Thunb). Steud. (Paulowniaceae) fruits analysis has led to discovery of 10 C-6 geranylated flavanones tomentodiplacone C–I and mimulone C–E.

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Highlights

► Isolation of 10 C-6 geranyl substituted flavanones. ► Their structural elucidation including the configuration at C-2. ► Analysis of artifacts formation. ► Analysis of anti-MRSA activity of selected compounds. ► Analysis of the ability to affect eukaryotic translation of chosen compounds.

Introduction

Prenylation plays an important role in the diversification of aromatic natural products, contributing to the description of more than 1000 prenylated polyphenols obtained from plants. The occurrence of prenylated flavonoids is rather limited in plant families such as Asteraceae, Berberidaceae, Cannabaceae, Capparaceae, Euphorbiaceae, Fabaceae, Guttiferae, Moraceae, Myrsinaceae, Rutaceae or Umbellifereae (Yazaki et al., 2009). The most frequent type of prenyl substitution of flavonoids is a 3,3-dimethylallyl side chain. Compounds with a C5 (isopentenyl) or C10 (geranyl) side chain are quite abundant compared to those with a C15 (farnesyl) or with a further modified (e.g., by oxidation, reduction, dehydration, cyclization, or hydroxylation) prenyl moiety which are not common in nature (Barron and Ibrahim, 1996, Epifano et al., 2007, Yazaki et al., 2009). The addition of an isoprenoid chain renders the derivate molecule more effective than the parent compound from a pharmacological point of view, probably because a prenyl group increases the lipophilicity and confers on the molecule a strong affinity for biological membranes (Botta et al., 2005, Epifano et al., 2007).

Paulownia tomentosa (Thunb.) Steud. (Paulowniaceae) is a deciduous tree, about 10–20 m tall, native to China. The leaves are large and heart-shaped; the flowers are pale violet, blossoming before leaves appear. The fruits are dry, reddish-brown capsules approximately 3–4 cm long, containing numerous tiny winged seeds that are dispersed by wind and water (Erbar and Gülden, 2011) Previous publications have reported the content of phenolic glycosides, acylglycerols, furanquinones, naphthoquinones, iridoids, lignans, and phytosterols in MeOH and EtOH extracts obtained from P. tomentosa (Damtoft and Jensen, 1999, Franzyk et al., 1999, Babula et al., 2006, Kobayashi et al., 2008, Si et al., 2008, Asai et al., 2009). Furthermore, P. tomentosa (Thunb). Steud. (Paulowniaceae) is a rich source of prenylated flavonoids. More than 20, mostly novel compounds with a prenyl or geranyl side chain at C-6 of the flavonoid skeleton have been isolated from the flowers, fruits and leaves of P. tomentosa (Jiang et al., 2004, Šmejkal et al., 2007, Šmejkal et al., 2008b, Asai et al., 2008, Kobayashi et al., 2008, Schneiderová et al., 2012). Only two compounds showed the presence of a five carbon side chain (Šmejkal et al., 2007, Asai et al., 2008); for the others a 10-carbon side chain was typical. Further, only a few compounds showed a geranyl moiety modified by hydroxylation at C-6″ or C-7″ (Šmejkal et al., 2007, Šmejkal et al., 2008b, Asai et al., 2008, Schneiderová et al., 2012).

The antioxidant, antibacterial, antiphlogistic and cytotoxic activities of P. tomentosa geranyl flavonoids have been described recently (Šmejkal et al., 2007, Šmejkal et al., 2008a, Šmejkal et al., 2008b, Šmejkal et al., 2010, Asai et al., 2008, Hošek et al., 2010, Kollár et al., 2011). It has also been discovered that the glandular hairs on its young reproductive organs contain flavonoids at concentrations over 1000 times greater than those on the surfaces of its young leaves (Kobayashi et al., 2008). Some seasonal variations in the concentrations of C-geranyl flavonoids have also been described (Holubová and Šmejkal, 2011).

In this paper we report the isolation and structural elucidation of 10 new C-geranylated flavanones (110) (Fig. 1) substituted at position C-6 of the flavanone skeleton using 1D and 2D NMR experiments as well as MS, UV, IR, and CD. All of the isolated compounds showed a geranyl modified by formation of heterocyclic moiety (6, 8, 9), carbonyl (13, 7, 10), hydroxyl (1, 5, 6, 810), or methoxyl (1, 2, 4, 5, 10) groups, respectively. We suppose that these compounds are not isolation artifacts.

The antimicrobial activity of some of the newly isolated compounds together with some previously obtained geranylated flavanones was tested against several Gram-negative and Gram-positive bacteria species, including methicillin-resistant Staphylococcus aureus strains, and showed varying degrees of activity.

Furthermore, some of the isolated compounds were tested to determine their ability to affect eukaryotic translation initiation via dual-luciferase reporter assay. The compounds tested showed little such ability.

Section snippets

Results and discussion

Compounds 110 were isolated as amorphous yellowish solids by the extensive chromatographic separation of the chloroform portion of an ethanolic extract of P. tomentosa fruits. The MeOH-soluble portion of the CHCl3 extract was chromatographed on silica gel. On the basis of TLC and HPLC analysis, similar fractions were combined to make up 20 fractions marked alphabetically from A to T. Fractions C, D, and F were further separated using column chromatography, preparative RP-HPLC, prep. TLC or

Concluding remarks

The data presented demonstrate that P. tomentosa is a rich source of multifarious geranylated flavonoids. Compounds 110 have been obtained from a natural source for the first time and their structures have been shown to possess unusually modified geranyl side chains at position C-6 of the flavanone nucleus. The antibacterial activity of compounds 13, 5, 8, 9, and 1116 against different MRSA strains was tested, showing geranylated flavanones with unmodified side chain as compounds with

General experimental procedures

UV spectra were recorded in MeOH using a JASCO J-810 spectrometer (13, 5, 8, and 9) and a UV/Vis Spectrometer Lambda 25 (PerkinElmer Instruments) (4, 6, 7 and 10). CD spectra were recorded on a JASCO J-810 spectrometer (MeOH; the molar elipticity Θλ values are presented). IR spectra were determined by the ATR method on a Nicolet Impact 400D FT-IR spectrophotometer. NMR spectra were recorded using a Bruker Avance 400 Ultrashield spectrometer operating at a frequency of 400 MHz (1H). NMR spectra

Acknowledgement

The financial support of this work by the IGA UVPS (Grant No. 7/2010/FaF to Alice Navrátilová and No. 54/2011/FaF to Zuzana Hanáková) is gratefully acknowledged.

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