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Toxins 2015, 7(11), 4507-4518; doi:10.3390/toxins7114507

Cytotoxic Indole Alkaloids against Human Leukemia Cell Lines from the Toxic Plant Peganum harmala

1
School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China
2
College of Chemical Engineering, Shenyang University of Chemical Technology, Shenyang 110142, China
*
Author to whom correspondence should be addressed.
Academic Editor: Kevin Welch
Received: 21 August 2015 / Revised: 24 September 2015 / Accepted: 16 October 2015 / Published: 3 November 2015
(This article belongs to the Collection Toxicity of Natural Alkaloids)
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Abstract

Bioactivity-guided fractionation was used to determine the cytotoxic alkaloids from the toxic plant Peganum harmala. Two novel indole alkaloids, together with ten known ones, were isolated and identified. The novel alkaloids were elucidated to be 2-(indol-3-yl)ethyl-α-L-rhamnopyranosyl-(1 → 6)-β-D-glucopyranoside (2) and 3-hydroxy-3-(N-acetyl-2-aminoethyl)-6-methoxyindol-2-one (3). The cytotoxicity against human leukemia cells was assayed for the alkaloids and some of them showed potent activity. Harmalacidine (compound 8, HMC) exhibited the highest cytotoxicity against U-937 cells with IC50 value of 3.1 ± 0.2 μmol/L. The cytotoxic mechanism of HMC was targeting the mitochondrial and protein tyrosine kinase signaling pathways (PTKs-Ras/Raf/ERK). The results strongly demonstrated that the alkaloids from Peganum harmala could be a promising candidate for the therapy of leukemia. View Full-Text
Keywords: Peganum harmala; indole alkaloids; cytotoxicity; anti-leukemia; mitochondrial pathway Peganum harmala; indole alkaloids; cytotoxicity; anti-leukemia; mitochondrial pathway
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MDPI and ACS Style

Wang, C.; Zhang, Z.; Wang, Y.; He, X. Cytotoxic Indole Alkaloids against Human Leukemia Cell Lines from the Toxic Plant Peganum harmala. Toxins 2015, 7, 4507-4518.

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