A Series of β-Carboline Alkaloids from the Seeds of Peganum harmala Show G-Quadruplex Interactions

Kai Bo Wang; Da Hong Li; Ping Hu; Wen Jing Wang; Clement Lin; Jian Wang; Bin Lin; Jiao Bai; Yue Hu Pei; Yong Kui Jing; Zhan Lin Li; Danzhou Yang; Hui Ming Hua

doi:10.1021/acs.orglett.6b01560

A Series of β-Carboline Alkaloids from the Seeds of Peganum harmala Show G-Quadruplex Interactions

Kai Bo Wang, Da Hong Li, Ping Hu, Wen Jing Wang, Clement Lin, Jian Wang, Bin Lin, Jiao Bai, Yue Hu Pei, Yong Kui Jing, Zhan Lin Li, Danzhou Yang, Hui Ming Hua

Pharmacology and Toxicology

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

In this study, we screened 17 medicinal plants for binding activity to G-quadruplex d(TTGGGTT)₄ by ¹H NMR spectroscopy and found that the crude extract of Peganum harmala L. seeds showed the most potential binding activity. Subsequently, ¹H NMR- and bioassay-guided isolation of the extract of P. harmala L. was performed to obtain four pairs of partially racemized β-carboline alkaloids, pegaharmines A-D (1-4). Their structures and absolute configurations were determined by extensive NMR analyses, X-ray crystallography, ECD calculations, and CD exciton chirality approaches. Interestingly, pegaharmine D (4), which showed the strongest G-quadruplex interaction, exhibited significant cytotoxic activity against three cancer cell lines. This work contributed a practical strategy for the discovery of novel G-quadruplex ligands from natural products and provided potential insights for using β-carboline alkaloids as anticancer lead compounds specifically targeting G-quadruplexes.

Original language	English (US)
Pages (from-to)	3398-3401
Number of pages	4
Journal	Organic Letters
Volume	18
Issue number	14
DOIs	https://doi.org/10.1021/acs.orglett.6b01560
State	Published - Jul 15 2016

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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A Series of β-Carboline Alkaloids from the Seeds of Peganum harmala Show G-Quadruplex Interactions. / Wang, Kai Bo; Li, Da Hong; Hu, Ping; Wang, Wen Jing; Lin, Clement; Wang, Jian; Lin, Bin; Bai, Jiao; Pei, Yue Hu; Jing, Yong Kui; Li, Zhan Lin; Yang, Danzhou; Hua, Hui Ming.

In: Organic Letters, Vol. 18, No. 14, 15.07.2016, p. 3398-3401.

Research output: Contribution to journal › Article › peer-review

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title = "A Series of β-Carboline Alkaloids from the Seeds of Peganum harmala Show G-Quadruplex Interactions",

abstract = "In this study, we screened 17 medicinal plants for binding activity to G-quadruplex d(TTGGGTT)4 by 1H NMR spectroscopy and found that the crude extract of Peganum harmala L. seeds showed the most potential binding activity. Subsequently, 1H NMR- and bioassay-guided isolation of the extract of P. harmala L. was performed to obtain four pairs of partially racemized β-carboline alkaloids, pegaharmines A-D (1-4). Their structures and absolute configurations were determined by extensive NMR analyses, X-ray crystallography, ECD calculations, and CD exciton chirality approaches. Interestingly, pegaharmine D (4), which showed the strongest G-quadruplex interaction, exhibited significant cytotoxic activity against three cancer cell lines. This work contributed a practical strategy for the discovery of novel G-quadruplex ligands from natural products and provided potential insights for using β-carboline alkaloids as anticancer lead compounds specifically targeting G-quadruplexes.",

author = "Wang, {Kai Bo} and Li, {Da Hong} and Ping Hu and Wang, {Wen Jing} and Clement Lin and Jian Wang and Bin Lin and Jiao Bai and Pei, {Yue Hu} and Jing, {Yong Kui} and Li, {Zhan Lin} and Danzhou Yang and Hua, {Hui Ming}",

note = "Funding Information: The work was financially supported by the National Natural Science Foundation of China (Grant No. 81172958), the China Scholarships Council, and the Basic Research Subject of Key Laboratory Supported by Educational Commission of Liaoning Province of China (No. LZ2014044). Publisher Copyright: {\textcopyright} 2016 American Chemical Society. Copyright: Copyright 2016 Elsevier B.V., All rights reserved.",

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AU - Lin, Clement

AU - Wang, Jian

AU - Lin, Bin

AU - Bai, Jiao

AU - Pei, Yue Hu

AU - Jing, Yong Kui

AU - Li, Zhan Lin

AU - Yang, Danzhou

AU - Hua, Hui Ming

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PY - 2016/7/15

Y1 - 2016/7/15

N2 - In this study, we screened 17 medicinal plants for binding activity to G-quadruplex d(TTGGGTT)4 by 1H NMR spectroscopy and found that the crude extract of Peganum harmala L. seeds showed the most potential binding activity. Subsequently, 1H NMR- and bioassay-guided isolation of the extract of P. harmala L. was performed to obtain four pairs of partially racemized β-carboline alkaloids, pegaharmines A-D (1-4). Their structures and absolute configurations were determined by extensive NMR analyses, X-ray crystallography, ECD calculations, and CD exciton chirality approaches. Interestingly, pegaharmine D (4), which showed the strongest G-quadruplex interaction, exhibited significant cytotoxic activity against three cancer cell lines. This work contributed a practical strategy for the discovery of novel G-quadruplex ligands from natural products and provided potential insights for using β-carboline alkaloids as anticancer lead compounds specifically targeting G-quadruplexes.

AB - In this study, we screened 17 medicinal plants for binding activity to G-quadruplex d(TTGGGTT)4 by 1H NMR spectroscopy and found that the crude extract of Peganum harmala L. seeds showed the most potential binding activity. Subsequently, 1H NMR- and bioassay-guided isolation of the extract of P. harmala L. was performed to obtain four pairs of partially racemized β-carboline alkaloids, pegaharmines A-D (1-4). Their structures and absolute configurations were determined by extensive NMR analyses, X-ray crystallography, ECD calculations, and CD exciton chirality approaches. Interestingly, pegaharmine D (4), which showed the strongest G-quadruplex interaction, exhibited significant cytotoxic activity against three cancer cell lines. This work contributed a practical strategy for the discovery of novel G-quadruplex ligands from natural products and provided potential insights for using β-carboline alkaloids as anticancer lead compounds specifically targeting G-quadruplexes.

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A Series of β-Carboline Alkaloids from the Seeds of Peganum harmala Show G-Quadruplex Interactions

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