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Planta Med 2019; 85(16): 1263-1274
DOI: 10.1055/a-1013-1417
Natural Product Chemistry and Analytical Studies
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Unusual Prenylated Stilbene Derivatives with PTP1B Inhibitory Activity from Artocarpus styracifolius

Wenyan Li
1   Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
,
Zhongji Pu
2   School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China
,
Wenfang Yi
1   Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
,
Qinge Ma
1   Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
,
Qinhua Lin
3   School of Pharmacy, Gannan Health Vocational College, Ganzhou, China
,
Guoyue Zhong
1   Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
,
Pengcheng Yao
1   Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
,
Gang Ren
1   Research Center of Natural Resources of Chinese Medicinal Materials and Ethnic Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
› Author Affiliations
Further Information

Publication History

received 29 May 2019
revised 28 August 2019

accepted 12 September 2019

Publication Date:
11 October 2019 (online)

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Abstract

In an effort to identify agents from natural products that inhibit protein tyrosine phosphatase 1B (PTP1B), 5 new prenylated stilbenes, (±)-styrastilbene A (1), styrastilbene B (2), and (±)-styrastilbenes C – E (3, 4, and 7), along with 4 known structurally related compounds (5, 6, 8, and 9), were isolated from the roots of Artocarpus styracifolius. Their structures were elucidated by spectroscopic methods, including 1D and 2D nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HRESIMS), ultraviolet (UV), and infrared (IR). Based on these isolates, a new plausible biosynthetic pathway for the unusual stilbene derivatives 3–8 with a tetracyclic ring system is proposed. Among these compounds, 1–3, 8, and 9 displayed significant PTP1B inhibitory effects with IC50 values ranging from 2.40 (95% confidence interval [CI]: 2.21 – 2.59) to 8.80 (95% CI: 8.28 – 9.32) µM. Moreover, kinetic analysis and molecular docking simulations were performed to provide insight into the inhibition type as well as the interaction and binding mode of these active isolates with PTP1B. Our results revealed mixed-type PTP1B inhibition for all compounds tested. Docking simulations of these stilbene derivatives showed negative binding energies and close proximity to residues at the allosteric and catalytic sites of PTP1B. These findings suggest that these compounds may have a potential to be further developed as agents for the management of type 2 diabetes mellitus.

Key words

Artocarpus styracifolius - Moraceae - prenylated stilbene - diabetes - PTP1B inhibitory activity - molecular docking

Supporting Information

    The spectra (1D and 2D NMR, UV, IR, and HRESIMS) of the new compounds 1 (Fig. 1S–15S), 2 (Fig. 16S–24S), 3 (Fig. 25S–34S), 4 (Fig. 35S–47S), and 7 (Fig. 48S–58S) are available as Supporting Information.

  • Supporting Information
 

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