Anti-inflammatory quinoline alkaloids from the root bark of Dictamnus dasycarpus
Graphical abstract
Six undescribed quinoline alkaloids, including a pair of enantiomers of dimeric furoquinoline alkaloid, along with 18 known ones were isolated from the root bark of Dictamnus dasycarpus. Their anti-inflammatory activities were evaluated.
Introduction
The root bark of Dictamnus dasycarpus Turcz. (Rutaceae), known as “Baixianpi” in Chinese, is a traditional Chinese medicine for the treatment of skin inflammation, eczema, rubella, rheumatism, and gynecologic inflammation (China Pharmacopoeia Committee, 2015), mainly grows in northeast China and Inner Mongolia. Previous phytochemical studies have revealed quinoline alkaloids and limonoids are the main characteristic constituents of D. dasycarpus (Du et al., 2005; Zhao et al., 1998). These alkaloids in D. dasycarpus have been reported to show various bioactivity, such as anti-inflammatory (Yoon et al., 2012; Gao et al., 2019), anti-cancer (Varamini et al., 2009), hepatoprotective (Yang and Chen, 2008), and neuroprotective effect (Jeong et al., 2010). Last decade, there are few reports about phytochemical study of D. dasycarpus, meanwhile, the mechanism remains to be researched. So, we have carried out a phytochemical investigation to search for more bioactive constituents from D. dasycarpus. In our continuing effort, 24 quinoline alkaloids (Fig. 1), including six undescribed quinoline alkaloids (dasycarine A–E), were obtained from D. dasycarpus. Of these, (±)-dasycarine A is a rare type of dimeric furoquinoline alkaloid via [2 + 2] cyclization of furan. Herein, the isolation, structural elucidation, and biological evaluation on the anti-inflammatory of all the compounds are reported.
Section snippets
Structural elucidation
(±)-dasycarine A (1) was obtained as a white amorphous powder with the molecular formula C24H18N2O4 established by HRESIMS (m/z 399.1341 [M + H]+, calcd. for C24H19N2O4, 399.1345). Its UV spectrum showed absorptions at 218, 229 and 311 nm, suggesting the presence of a quinoline skeleton similar to dictamnine (Yang et al., 2011; Fauvel et al., 1981). A set of ortho-disubstituted phenyl protons [δH 8.11 (1H, d, J = 7.8 Hz, H-5), 7.74 (1H, d, J = 7.8 Hz, H-8), 7.66 (1H, t, J = 7.8 Hz, H-7) and
Conclusions
Six previously undescribed quinoline alkaloids, as well as 18 known analogues, were isolated and identified from the 95% aqueous EtOH of D. dasycarpus. The rare dimer (1) of dictamnine via [2 + 2] cycloaddition was reported for the first time here. Through biological screening, some of the isolated alkaloids showed NO inhibition, which supply the proof for the traditional use and reference for the future research and development of D. dasycarpus.
General experimental procedures
UV spectra were recorded on a Shimadzu UV-2450 spectrophotometer (Shimadzu Co., Tokyo, Japan). IR spectra were obtained on a Thermo Nicolet Nexus 470 FT-IR spectrometer (MA, USA). NMR spectra were recorded on a Varian INOVA-500 (Varian Co., USA) and a Bruker Avance-400 FT NMR spectrometer (Bruker Co., Switzerland), and the chemical shifts were referenced to the solvent residual peak. HRESIMS data were determined on a Waters Xevo G2 Q-TOF mass spectrometer (Waters Co., Milford, MA, USA). The
Declaration of competing interest
The authors declare no competing financial interest.
Acknowledgments
This work was financially supported by the National Key Technology R&D Programs “New Drug Innovation” of China (No. 2018ZX09711001-008-003), National Traditional Chinese Medicine Standardization Project (No. 2017-110108-83-03-001423) and National Key Research and Development Project (No. 2018YFC1707300). We also thank A/Prof. D.C Xiong for his kind help.
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These authors contributed equally.