Aporphine and phenanthrene alkaloids with antioxidant activity from the roots of Stephania tetrandra

doi:10.1016/j.fitote.2020.104551

Fitoterapia

Volume 143, June 2020, 104551

https://doi.org/10.1016/j.fitote.2020.104551 Get rights and content

Abstract

Five new alkaloids (1–5), including three new aporphine alkaloids and two new phenanthrene alkaloids, together with 10 known compounds (6–15) were obtained from the roots of Stephania tetrandra. Their structures were elucidated by spectroscopic methods, single-crystal X-ray diffraction, and electronic circular dichroism analyses. Compounds 7–10, and 13 showed antioxidant activities with malondialdehyde (MDA) inhibitory rates of 62.50 ± 1.91 to 98.44 ± 0.34% at the concentration of 10 μM.

Graphical abstract

Introduction

Stephania tetrandra S. Moore (Menispermaceae) is a traditional Chinese medicinal plant, and its roots are used for treatment of rheumatalgia, dropsy, dysuria, and eczema [1]. Previous phytochemical investigations on this plant revealed that alkaloids were the main constituents [[2], [3], [4], [5], [6], [7]], including bisbenzylisoquinoline alkaloids, aporphine alkaloids, phenanthrene alkaloids, and protoberberine alkaloids. Some of these compounds showed the anti-acetylcholinesterase [6], anti-inflammatory [8], anti-hyperglycemic [9], antioxidant [10], and anticancer activities [11,12]. As part of our work to study traditional Chinese medicine, an investigation was performed on the roots of Stephania tetrandra. The crude extract exhibited significant antioxidant activity. Therefore, the chemical constituents in the active portions and their antioxidant activity were investigated. This led to the isolation of 15 alkaloids (Fig. 1), including three new aporphine alkaloids, two new phenanthrene alkaloids and 10 known analogues. Herein, the isolation, structural elucidation, and bioactivity evaluation of these compounds are reported.

Section snippets

General experimental procedures

UV spectra were obtained in MeOH on a JASCO V-650 spectrophotometer (JASCO, Japan). Optical rotations were measured using a JASCO P-2000 automatic digital polarimeter (JASCO, Japan). ECD spectra were tested on a JASCO J-815 spectrometer (JASCO, Japan). Melting points were recorded on an XT5B microscope melting point apparatus (Beijing Keyi Electro-optical Instrument Factory, China). IR spectra were measured by a Nicolet 5700 spectrometer (Thermo Fisher Scientific, USA). The NMR data were

Results and discussion

Compound 1 was obtained as colorless crystals. The IR spectrum suggested the presence of amidic (1641 cm⁻¹) functionality. Its molecular formula was determined to be C₂₁H₂₁O₅N by the HRESIMS ion at m/z 368.1486 [M + H]⁺ (calcd for C₂₁H₂₂O₅N, 368.1492), implying 12 degrees of unsaturation. In addition, a weak ion peak at m/z 309.1117 was observed due to loss of (N-COCH₃ + H) from the molecular. These data indicated that the amidic functionality was in the shape of N-acetyl group. The 1D NMR data

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

This work was financially supported by Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine [CAMS-12M-1-010], the State Key Laboratory of Bioactive Substance and Function of Natural Medicines [No. GTZA201803], and the Drug Innovation Major Project [2018ZX09711001-008-009].

References (26)

H.S. Choi et al.
J. Ethnopharmacol.
(2000)
H.S. Lee et al.
Toxicol. Appl. Pharmacol.
(2017)
J. Frelek et al.
Tetrahedron Asymmetry
(1999)
M. Gerards et al.
Tetrahedron Asymmetry
(1990)
S.T. Lu et al.
Phytochemistry
(1985)
National Pharmacopoeia Committee
Pharmacopoeia of Peoples Republic of China [M]. Part 1
(2015)
T.M. Hu et al.
Acta Pharm. Sin.
(1986)
T. Ogino et al.
Heterocycles
(1988)
J.Z. Deng et al.
J. Nat. Prod.
(1990)
D.Y. Si et al.
J. Nat. Prod.
(1992)

T. Ogino et al.

Heterocycles

(1997)

T. Ogino et al.

Heterocycles

(1998)

T. Tsutsumi et al.

Biol. Pharm. Bull.

(2003)

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An integrated strategy for characterization of chemical constituents in Stephania tetrandra using LC–QTOF–MS/MS and the target isolation of two new biflavonoids
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Natural source: Stephania tetrandra85Unlabelled Image 13C NMR (150 MHz, CDCl3)85: (E): 142.9 (C-1), 126.6 (C-1a), 126.2 (C-1b), 152.0 (C-2), 111.9 (C-3), 130.9 (C-3a), 29.8 (C-4), 36.2 (C-5), 54.2 (C-6a), 38.7 (C-7), 129.0 (C-7a), 119.8 (C-8), 111.5 (C-9), 150.0 (C-10), 144.5 (C-11), 119.7 (C-11a), 62.1 (1-OCH3), 56.3 (2-OCH3), 56.2 (10-OCH3), 162.0 (CHO). 13C NMR (150 MHz, CDCl3)85: (Z): 143.2 (C-1), 127.0 (C-1a), 126.7 (C-1b), 151.8 (C-2), 111.6 (C-3), 129.8 (C-3a), 31.1 (C-4), 42.1 (C-5), 49.9 (C-6a), 35.2 (C-7), 129.7 (C-7a), 120.1 (C-8), 111.6 (C-9), 149.7 (C-10), 144.4 (C-11), 119.6 (C-11a), 62.1 (1-OCH3), 56.3 (2-OCH3), 56.2 (10-OCH3), 162.2 (CHO).
This study involves aporphine alkaloids identified through ¹³C Nuclear Magnetic Resonance (NMR) spectroscopic data. For the present publication, articles were selected from several databases on aporphine alkaloids from 1994 to 2021. In this class, more than 700 compounds have been registered, with 221 were included in this section, among which 122 were characterized for the first time in the investigated period. The study also addresses their biosynthetic pathways, classifying substances according to their structural characteristics based on established literature. Furthermore, pharmacological activities related to the aporphine alkaloids highlighted in this section are also presented, giving an overview of the various applications of these compounds.

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Aporphine and phenanthrene alkaloids with antioxidant activity from the roots of Stephania tetrandra

Abstract

Graphical abstract

Introduction

Section snippets

General experimental procedures

Results and discussion

Declaration of Competing Interest

Acknowledgments

J. Ethnopharmacol.

Toxicol. Appl. Pharmacol.

Tetrahedron Asymmetry

Tetrahedron Asymmetry

Phytochemistry

Pharmacopoeia of Peoples Republic of China [M]. Part 1

Acta Pharm. Sin.

Heterocycles

J. Nat. Prod.

J. Nat. Prod.

Heterocycles

Heterocycles

Biol. Pharm. Bull.