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Shu Zhen Mu
Guizhou University
Corresponding Author
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Zanthoxylum nitidium (Roxb.) DC (Rutaceae) is well known for inhibiting the proliferation of human gastric, liver, kidney and lung cancer cells, though research on its potential use in treating leukaemia is relatively rare. Twenty-six compounds were isolated from the chloroform and petroleum ether extracts of the roots and leaves of Z. nitidium. They were (+)-9′-O-transferuloyl-5, 5′-dimethoxylaricriresinol (1), 8-(3′-oxobut-1′-en-1′-yl)-5, 7-trimethoxy-coumarin (2), 5, 7, 8-trimethoxy-coumarin (3), 5-(3′, 3′-dimethyl-2′-butenyloxy)-7, 8-dimethoxy-coumarin (4), 2-(5-methoxy-2-methyl-1H-indol-3-yl) methyl acetate (5), 2′-(5,6-dihydrochleletrythrine-6-yl) ethyl acetate (6), 6-acetonyldi-hydrochelerythrine (7), 6β-hydroxymethyldihydronitidine (8), bocconoline (9), zanthoxyline (10), O-methylzanthoxyline (11), rhoifoline B (12), N-nornitidine (13), nitidine (14), chelerythrine (15), 4-hydroxyl-7,8-dimethoxy-furoquinoline (16), dictamnine (17), γ-fagarine (18), skimmianine (19), robustine (20), R-(+)-platydesmine (21), 4-O-methyl-1-methyl-quinoline-2-one (22), 4-methoxy-2-quinolone (23), liriodenine (24), aurantiamide acetate (25), 10-O-demethyl-12-O-methylarnottianamide (26). Four among them, compounds 4-6 and 16, were first confirmed in this study by UV, IR, 1D, 2D NMR and HR-ESI-MS spectra. Compounds 1-2 and 11 were isolated from Z. nitidium for the first time. Of the assayed compounds, 1, 2, 9, 10, 14, 15 and 24, exhibited good inhibitory activities in the leukaemia cell line HEL, whereas compound 14 (IC50: 3.59 µM) and compound 24 (IC50: 15.95 µM) exhibited potent inhibitory activities. So, to further investigate the possible mechanisms, cell cycle and apoptosis assays were performed, which indicated that compound 14 causes obvious S-phase arrest in HEL cells and induced apoptosis, whereas compound 24 only induced apoptosis. The present results suggested both compounds 14 and 24 are promising potential anti-leukaemia drug candidates.
Keywords
Zanthoxylum nitidium, alkaloids, benzophenanthrene, leukaemia, HEL cell, cell cycle, cell apoptosis
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Received 22 Mar, 2020
Editorial decision: Major revision
On 22 Mar, 2020
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Received 17 Mar, 2020
Reviewer #4 agreed
On 11 Mar, 2020
Reviewer #3 agreed
On 09 Mar, 2020
Reviewer #2 agreed
On 09 Mar, 2020
Reviewer #1 agreed
On 24 Feb, 2020
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This preprint is under consideration at BMC Chemistry. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Shu Zhen Mu
Guizhou University
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Review
No community comments so far
Editor assigned
On 14 Dec, 2020
Submission checks complete
On 14 Dec, 2020
Editor invited
On 14 Dec, 2020
No comments provided
Editorial decision: Minor revision
On 29 Nov, 2020
Editor assigned
On 06 Nov, 2020
Submission checks complete
On 06 Nov, 2020
Editor invited
On 06 Nov, 2020
Version 4
Posted 16 Aug, 2020
No comments provided
Editorial decision: Major revision
On 08 Sep, 2020
Review #2 received
Received 07 Sep, 2020
Review #1 received
Received 21 Aug, 2020
Reviewer #2 agreed
On 18 Aug, 2020
Reviewers invited
Invitations sent on 17 Aug, 2020
Reviewer #1 agreed
On 17 Aug, 2020
Editor assigned
On 13 Aug, 2020
Submission checks complete
On 12 Aug, 2020
Editor invited
On 12 Aug, 2020
No comments provided
Review #1 received
Received 23 Jul, 2020
Editorial decision: Major revision
On 23 Jul, 2020
Review #3 received
Received 22 Jul, 2020
Review #2 received
Received 22 Jul, 2020
Reviewer #3 agreed
On 14 Jul, 2020
Reviewer #2 agreed
On 13 Jul, 2020
Reviewer #1 agreed
On 03 Jul, 2020
Editor assigned
On 30 Jun, 2020
Reviewers invited
Invitations sent on 30 Jun, 2020
Submission checks complete
On 29 Jun, 2020
Editor invited
On 29 Jun, 2020
No comments provided
Editorial decision: Major revision
On 09 Jun, 2020
Review #1 received
Received 29 May, 2020
Review #2 received
Received 20 May, 2020
Reviewer #2 agreed
On 04 May, 2020
Reviewer #1 agreed
On 03 May, 2020
Editor assigned
On 16 Apr, 2020
Reviewers invited
Invitations sent on 16 Apr, 2020
Submission checks complete
On 15 Apr, 2020
Editor invited
On 15 Apr, 2020
No comments provided
Review #2 received
Received 22 Mar, 2020
Editorial decision: Major revision
On 22 Mar, 2020
Review #1 received
Received 17 Mar, 2020
Reviewer #4 agreed
On 11 Mar, 2020
Reviewer #3 agreed
On 09 Mar, 2020
Reviewer #2 agreed
On 09 Mar, 2020
Reviewer #1 agreed
On 24 Feb, 2020
Reviewers invited
Invitations sent on 29 Jan, 2020
Editor assigned
On 28 Jan, 2020
Submission checks complete
On 27 Jan, 2020
Editor invited
On 27 Jan, 2020
First submitted
On 23 Jan, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Organic Chemistry
License:
This work is licensed under a CC BY 4.0 License. Read Full License
The most recent version of this article is available here.
Zanthoxylum nitidium (Roxb.) DC (Rutaceae) is well known for inhibiting the proliferation of human gastric, liver, kidney and lung cancer cells, though research on its potential use in treating leukaemia is relatively rare. Twenty-six compounds were isolated from the chloroform and petroleum ether extracts of the roots and leaves of Z. nitidium. They were (+)-9′-O-transferuloyl-5, 5′-dimethoxylaricriresinol (1), 8-(3′-oxobut-1′-en-1′-yl)-5, 7-trimethoxy-coumarin (2), 5, 7, 8-trimethoxy-coumarin (3), 5-(3′, 3′-dimethyl-2′-butenyloxy)-7, 8-dimethoxy-coumarin (4), 2-(5-methoxy-2-methyl-1H-indol-3-yl) methyl acetate (5), 2′-(5,6-dihydrochleletrythrine-6-yl) ethyl acetate (6), 6-acetonyldi-hydrochelerythrine (7), 6β-hydroxymethyldihydronitidine (8), bocconoline (9), zanthoxyline (10), O-methylzanthoxyline (11), rhoifoline B (12), N-nornitidine (13), nitidine (14), chelerythrine (15), 4-hydroxyl-7,8-dimethoxy-furoquinoline (16), dictamnine (17), γ-fagarine (18), skimmianine (19), robustine (20), R-(+)-platydesmine (21), 4-O-methyl-1-methyl-quinoline-2-one (22), 4-methoxy-2-quinolone (23), liriodenine (24), aurantiamide acetate (25), 10-O-demethyl-12-O-methylarnottianamide (26). Four among them, compounds 4-6 and 16, were first confirmed in this study by UV, IR, 1D, 2D NMR and HR-ESI-MS spectra. Compounds 1-2 and 11 were isolated from Z. nitidium for the first time. Of the assayed compounds, 1, 2, 9, 10, 14, 15 and 24, exhibited good inhibitory activities in the leukaemia cell line HEL, whereas compound 14 (IC50: 3.59 µM) and compound 24 (IC50: 15.95 µM) exhibited potent inhibitory activities. So, to further investigate the possible mechanisms, cell cycle and apoptosis assays were performed, which indicated that compound 14 causes obvious S-phase arrest in HEL cells and induced apoptosis, whereas compound 24 only induced apoptosis. The present results suggested both compounds 14 and 24 are promising potential anti-leukaemia drug candidates.
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