Elsevier

Fitoterapia

Volume 145, September 2020, 104628
Fitoterapia

Tunicyclin L, a cyclic peptide from Psammosilene tunicoides: Isolation, characterization, conformational studies and biological activity

https://doi.org/10.1016/j.fitote.2020.104628Get rights and content

Highlights

  • A new cyclic peptide and eleven known compounds were isolated from Psammosilene tunicoides.

  • The single crystal X-ray diffraction study revealed the stereochemistry of the 24-membered ring cyclic peptide (1).

  • Compound 6 was a new natural product,and compounds 3, 4, and 11 were isolated from this plant for the first time.

  • Compounds 1, 3, 4, 7, and 9 showed moderate anti-acetylcholinesterase (AChE) activity.

Abstract

Tunicyclin L (1), cyclo (L-Pro1-Gly-L-Phe1-L-Ile-L-Pro2-L-Phe2 -L-Thr-L-Val), and 11 known compounds, including one cyclic peptide (2), eight carboline alkaloids (310), one lignan (11) and one flavone (12) were isolated from the roots of Psammosilene tunicoides. Their structures were elucidated on the basis of extensive UV, IR, MS, NMR spectroscopic data and comparison with literature. Single-crystal X-ray diffraction results revealed the stereochemistry of the 24-membered ring cyclic peptide (1). Among these known compounds, compound 6 was found to be a new natural product, and compounds 3, 4, and 11 were isolated from this plant for the first time. Five compounds (1, 3, 4, 7, and 9) showed moderate anti-acetylcholinesterase (AChE) activity.

Introduction

Psammosilene tunicoides (W. C. Wu et C. Y. Wu) is a monotype genus plant of the Caryophyllaceae family and is a well-known medicinal herb used as an analgesic and hemostatic agent in the southwest of China. Currently, this plant is one of the ingredients used in a famous Chinese traditional medicine formulation “Yunnan Baiyao” [1]. Phytochemical studies on P. tunicoides have led to the isolation and identification of triterpenoid saponins [2], β-carboline alkaloids [3,4] and cyclic peptides [5,6], which exhibit diverse biological activities, such as antibacterial [7] and immunomodulator [8] properties. At present, about 20 cyclic peptides have been isolated and identified, such as cyclo (Pro-Val), cyclo (Pro-Ala), cyclo (Pro-Pro) [9], cyclo (Ala-Ala), cyclo (Ala-Val), cyclo (Ala-Leu), cyclo (Ala-Ile) [10], psammosilenin A, psammosilenin B [11], and tunicyclin A-K [12,13]. Among them, a few have shown excellent biological profiles including tunicyclin D and psammosilenin A. Tunicyclin D showed a broad spectrum of antifungal activity against Candida albicans (SC5314), Candida albicans (Y0109), Candida tropicalis, Candida parapsilosis, and Cryptococcus neoformans (BLS108) with MIC80 values of 4.0, 16.0, 0.25, 1.0, and 1.0 μg·mL−1, respectively [7]. Psammosilenin A was found to possess potent cytotoxic activity against DLA and EAC cell with IC50 value of 7.93 and 17.06 μM, respectively. Furthermore, good anthelmintic activity against earthworms M. konkanensis and Eudrilus species at 1 and 2 mg·mL−1 [14]. For the sake of searching novel bioactive constituents from this herb, phytochemical investigations were conducted in the present study. In this paper, 12 compounds were isolated and characterized, including an undescribed cyclic peptide and eleven known components (Fig. 1). AChE plays a vital role in the treatment of Alzheimer's disease. Cyclic peptides as a potential sources of novel compounds, exhibit AChE inhibitory property like beauvericin and cyclo (L-Phe-L-Leu-L-Val-L-Leu-L-Leu), with IC50 values of 3.09 and 5.87 μΜ, respectively [15]. The anti-acetylcholinesterase (AChE) activities of compounds 112 were evaluated. Molecular docking research was applied to predict the possible mechanism of some active compounds.

Section snippets

General experimental procedures

1H (600 MHz), 13C (150 MHz), and 2D (1H-1H COSY, HSQC, and HMBC) NMR spectra were recorded using a Bruker AV 600 spectrometer (Bruker Corporation, Fallanden, Switzerland) with TMS as an internal reference and using DMSO d6 as solvents. The IR spectra (KBr) were recorded by an Equinox 55 FT-IR spectrometer (Bruker Optics Inc., MA, USA). The TOF-MS-ES data were obtained using a Waters ACQUITY™ UPLC-Q-TOF-MS (Waters Corp., Milford, USA). UPLC-Q-TOF-MS/MS data were obtained using a Bruker Agilent

Structure determination of new and known compounds

Chromatographic separation the EtOAc extract of the roots of P. tunicoides yielded one new cyclopeptide (1) and 11 known compounds (211). By comparing the NMR spectroscopic data obtained from these compounds with values reported in the literature, these known compounds were identified as tunicyclin E (2) [6], 9H-pyrido [3,4-β] indole-3-carboxamide (3) [18], stellarine A (4) [19], stellarine C (5) [8], 1-acetyl-3-ethoxycarbonyl-β-carboline (6) [20],

Conclusions

In conclusion, the present work reported an undescribed cyclic peptide 1 along with eleven known compounds all obtained from P. tunicoides. The structures of these compounds were elucidated by analysis of NMR, MS spectroscopic data. Single crystal X-ray diffraction study revealed the stereochemistry of the 24-membered ring cyclic peptide (1). Biological studies demonstrated that compounds 1, 3, 4, 7, and 9 showed moderate inhibitory activity against AChE in vitro. The molecular docking results

Declaration of Competing Interest

The authors declare no conflict of interest.

Acknowledgments

Authors are thankful for Dr. Bona Dai and Dr. Lingling Li at Instrumental Analysis Center of Shanghai Jiao Tong University for spectral measurements and X-ray spectral measurements, respectively.

References (29)

  • J.M. Tian et al.

    Carboline alkaloids from Psammosilene tunicoides and their cytotoxic activities

    Planta Med.

    (2012)
  • J.M. Tian et al.

    Tunicyclin A, the first plant tricyclic ring cycloheptapeptide from Psammosilene tunicoides

    Org. Lett.

    (2009)
  • J.M. Tian et al.

    Experimental and computational insights into the conformations of tunicyclin E, a new cycloheptapeptide from Psammosilene tunicoides

    RSC Adv.

    (2012)
  • J.M. Tian et al.

    Antifungal cyclic peptides from Psammosilene tunicoides

    J. Nat. Prod.

    (2010)
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