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An integrated strategy for the systematic characterization and discovery of new indole alkaloids from Uncaria rhynchophylla by UHPLC/DAD/LTQ-Orbitrap-MS

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Abstract

The exploration of new chemical entities from herbal medicines may provide candidates for the in silico screening of drug leads. However, this significant work is hindered by the presence of multiple classes of plant metabolites and many re-discovered structures. This study presents an integrated strategy that uses ultrahigh-performance liquid chromatography/linear ion-trap quadrupole/Orbitrap mass spectrometry (UHPLC/LTQ-Orbitrap-MS) coupled with in-house library data for the systematic characterization and discovery of new potentially bioactive molecules. Exploration of the indole alkaloids from Uncaria rhynchophylla (UR) is presented as a model study. Initially, the primary characterization of alkaloids was achieved using mass defect filtering and neutral loss filtering. Subsequently, phytochemical isolation obtained 14 alkaloid compounds as reference standards, including a new one identified as 16,17-dihydro-O-demethylhirsuteine by NMR analyses. The direct-infusion fragmentation behaviors of these isolated alkaloids were studied to provide diagnostic structural information facilitating the rapid differentiation and characterization of four different alkaloid subtypes. Ultimately, after combining the experimental results with a survey of an in-house library containing 129 alkaloids isolated from the Uncaria genus, a total of 92 alkaloids (60 free alkaloids and 32 alkaloid O-glycosides) were identified or tentatively characterized, 56 of which are potential new alkaloids for the Uncaria genus. Hydroxylation on ring A, broad variations in the C-15 side chain, new N-oxides, and numerous O-glycosides, represent the novel features of the newly discovered indole alkaloid structures. These results greatly expand our knowledge of UR chemistry and are useful for the computational screening of potentially bioactive molecules from indole alkaloids.

A four-step integrated strategy for the systematic characterization and efficient discovery of new indole alkaloids from Uncaria rhynchophylla

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Abbreviations

DPIs:

Diagnostic product ions

ESI-CID-MSn :

Electrospray ionization–collision-induced dissociation–tandem mass spectrometric fragmentation

MDF:

Mass defect filtering

NLF:

Neutral loss filtering

pMIA:

Pentacyclic monoterpene indole alkaloids

RDBeq:

Ring double-bond equivalent

tMIA:

Tetracyclic monoterpene indole alkaloids

tMIN:

Tetracyclic monoterpene indole N-oxides

tMOA:

Tetracyclic monoterpene oxindole alkaloids

UHPLC/LTQ-Orbitrap:

Ultra-high performance liquid chromatography/linear ion-trap quadrupole/Orbitrap

UR:

Uncaria rhynchophylla

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Acknowledgments

The authors acknowledge the financial support from the Twelfth Five-Year National Science & Technology Support Program (2012BAI29B06), the National Science and Technology Major Project for Major Drug Development (2013ZX09508104 and 2014ZX09304-307-001-007), and Special Scientific Research in the Chinese Medicine Industry of State Administration of Traditional Chinese Medicine (201307002).

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    Authors and Affiliations

    1. Shanghai Research Center for Modernization of Traditional Chinese Medicine, National Engineering Laboratory for TCM Standardization Technology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Haike Road 501, Shanghai, 201203, China

      Huiqin Pan, Wenzhi Yang, Yibei Zhang, Min Yang, Ruihong Feng, Wanying Wu & Dean Guo

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    1. Huiqin Pan
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    2. Wenzhi Yang
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    3. Yibei Zhang
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    4. Min Yang
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    6. Wanying Wu
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    7. Dean Guo
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    Correspondence to Wanying Wu or Dean Guo.

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    Huiqin Pan and Wenzhi Yang contributed equally to this work.

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    Pan, H., Yang, W., Zhang, Y. et al. An integrated strategy for the systematic characterization and discovery of new indole alkaloids from Uncaria rhynchophylla by UHPLC/DAD/LTQ-Orbitrap-MS. Anal Bioanal Chem 407, 6057–6070 (2015). https://doi.org/10.1007/s00216-015-8777-0

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