Activity-guided isolation of the chemical constituents of Muntingia calabura using a quinone reductase induction assay

doi:10.1016/S0031-9422(03)00112-2

Phytochemistry

Volume 63, Issue 3, June 2003, Pages 335-341

https://doi.org/10.1016/S0031-9422(03)00112-2 Get rights and content

Abstract

Activity-guided fractionation of an EtOAc-soluble extract of the leaves of Muntingia calabura collected in Peru, using an in vitro quinone reductase induction assay with cultured Hepa 1c1c7 (mouse hepatoma) cells, resulted in the isolation of a flavanone with an unsubstituted B-ring, (2R,3R)-7-methoxy-3,5,8-trihydroxyflavanone (5), as well as 24 known compounds, which were mainly flavanones and flavones. The structure including absolute stereochemistry of compound 5 was determined by spectroscopic (HRMS, 1D and 2D NMR, and CD spectra) methods. Of the isolates obtained, in addition to 5, (2S)-5-hydroxy-7-methoxyflavanone, 2′,4′-dihydroxychalcone, 4,2′,4′-trihydroxychalcone, 7-hydroxyisoflavone and 7,3′,4′-trimethoxyisoflavone were found to induce quinone reductase activity.

A flavanone with an unsubstituted B ring, (2R,3R)-7-methoxy-3,5,8-trihydroxyflavanone, as well as 24 known compounds, were isolated from an EtOAc-soluble extract of the leaves of Multingia calabura. All isolates were evaluated for their potential cancer chemopreventive properties using a quinone reductase induction assay.

Introduction

Induction of Phase 2 drug-metabolizing enzymes such as quinone reductase (QR) is considered an effective strategy for achieving protection against the toxic and neoplastic effects of many carcinogens (Gerhauser et al., 1997, Talalay, 2000). As part of our continuing search for novel, plant-derived cancer chemopreventive agents (Pezzuto, 1997, Kinghorn et al., 1998, Pezzuto et al., 1999), the leaves of Muntingia calabura L. (Elaeocarpaceae), collected in Peru, were chosen for detailed investigation since their EtOAc-soluble extract significantly induced QR with cultured Hepa 1c1c7 (mouse hepatoma) cells. Various parts of this tree have several documented medicinal uses in both Southeast Asia and tropical America (Kaneda et al., 1991, Nshimo et al., 1993). The roots have been employed as an emmenogogue in Vietnam and as an abortifacient in Malaysia. In the Philippines, the flowers of this species have been used to treat headaches, and as an antidyspeptic, antispasmodic, and diaphoretic. Infusions of the flowers of this plant are drunk as a tranquillizer and tonic in Colombia (Perez-Arbelaez, 1975, Kaneda et al., 1991).

In our previous work, several cytotoxic flavonoids and chalcones were isolated from the roots (Kaneda et al., 1991) and the leaves and stems (Nshimo et al., 1993) of this species collected in the Philippines and in Thailand, respectively. Other phytochemical investigations on this plant have resulted in the isolation of flavones and ellagic acid (Seetharaman, 1990). The volatile phenolic, sesquiterpene and furanoid constituents of the ripe fruits of M. calabura have been analyzed by GC–MS (Wong et al., 1996). This paper describes the isolation and structure elucidation of 24 known compounds, (1–4, 6–14), and a new flavanone, (2R,3R)-7-methoxy-3,5,8-trihydroxyflavanone (5), obtained using the QR induction assay to monitor fractionation (Chang et al., 1997, Dinkova-Kostova & Talalay, 2000). The purified isolates from M. calabura were individually evaluated for their effects on QR induction.

Section snippets

Results and discussion

Fractionation of an EtOAc-soluble extract of the leaves of M. calabura with the QR induction assay led to the purification of a new flavanone, (2R,3R)-7-methoxy-3,5,8-trihydroxyflavanone (5), as well as 24 known compounds, (2S)-7-hydroxyflavanone (1) (Tansrisever et al., 1987, Hsieh et al., 1998a), (2S)-5,7-dihydroxyflavanone (pinocembrin, 2) (Ichino et al., 1988, Hsieh et al., 1998b), (2R,3R)-3,5,7-trihydroxyflavanone (pinobanksin, 3) (Kuroyanagi et al., 1982), (2S

General

Melting points were determined on a Fisher-Johns melting point apparatus and are uncorrected. Optical rotations were measured with a Perkin-Elmer 241 automatic polarimeter. The UV spectrum was obtained with a Beckman DU-7 spectrometer. The IR spectrum was run on an ATI Mattson Genesis Series FT-IR spectrophotometer. CD measurements were performed using a JASCO-710 CD spectropolarimeter. NMR spectral data were recorded at room temperature on a Bruker Avance DPX-300, NCM-360, or DRX-500 MHz

Acknowledgements

This work was supported by Program Project P01 CA48112 funded by the National Cancer Institute, NIH, Bethesda, MD. We are grateful to Drs. J. A. (Art) Anderson, Research Resources Center, University of Illinois at Chicago, and K. Fagerquist, Mass Spectrometry Facility, Department of Chemistry, University of Minnesota, Minneapolis, MN, for mass spectral data.

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Activity-guided isolation of the chemical constituents of Muntingia calabura using a quinone reductase induction assay

Abstract

Introduction

Section snippets

Results and discussion

General

Acknowledgements

Phytochemistry

Free Radical Biol. Med.

Phytochemistry

Phytochemistry

Determination of aglycone chirality in flavanone glycosides. Tetrahedron

Phytochemistry

Phytochemistry

Tetrahedron Lett.

Tetrahedron

Phytochemistry

Tetrahedron

Bioorg. Med. Chem. Lett.

Phytochemistry

Biochem. Pharmacol.

Phytochemistry

Phytochemistry

Cancer Lett.

Studies on cancer chemoprevention by traditional folk medicines. XXV. Inhibitory effect of isoliquiritigenin on azoxymethane-induced murine colon aberrant crypt focus formation and carcinogenesis

Biol. Pharm. Bull.

Resorcinol derivatives and flavonoids of Ononis natrix subspecies ramosissima

J. Nat. Prod.

Additional flavonoids from the leaves of Larrea tridentata

Planta Med.

Activity-guided isolation of constituents of Tephrosia purpurea with the potential to induce the phase II enzyme, quinone reductase

J. Nat. Prod.

Two antimicrobial flavanones from the leaves of Glycyrrhiza glabra

Chem. Pharm. Bull.

Cancer chemopreventive potential of sulforamate, a novel analogue of sulforaphane that induces phase 2 drug-metabolizing enzymes

Cancer Res.

Activity-guided isolation of constituents of Renealmia nicolaioides with the potential to induce the phase II enzyme quinone reductase

J. Nat. Prod.

B-ring unsubstituted flavones from Gnaphalium obtusifolium

Tetrahedron Lett.