期刊
TOXINS
卷 7, 期 11, 页码 4507-4518出版社
MDPI
DOI: 10.3390/toxins7114507
关键词
Peganum harmala; indole alkaloids; cytotoxicity; anti-leukemia; mitochondrial pathway
资金
- National Natural Science Foundation of China [U1203103, 81573303]
- Natural Science Foundation of Guangdong province [2014A030313588]
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--l-rhamnopyranosyl-(1 6)--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 mol/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.
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