title: Cytotoxic indole alkaloids against human leukemia cell lines from the toxic plant Peganum harmala.
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.
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. wangchunhua@whu.edu.cn.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Wang
authors.affiliation: College of Chemical Engineering, Shenyang University of Chemical Technology, Shenyang 110142, China. zhangzhenxue02@hotmail.com.
authors.forename: Zhenxue
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. wangyihai@whu.edu.cn.
authors.forename: Yihai
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China. hexiangjiu@163.com.
authors.forename: Xiangjiu
authors.initials: X
authors.lastname: He
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D026121:Indole Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D007938:Leukemia / Q000188:drug therapy*; D008928:Mitochondria / Q000187:drug effects; D032443:Peganum / Q000737:chemistry*; D011505:Protein-Tyrosine Kinases / Q000187:drug effects; D012639:Seeds / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D020298:U937 Cells
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D026121:Indole Alkaloids; D000255:Adenosine Triphosphate; D011505:Protein-Tyrosine Kinases
keywords: Peganum harmala; anti-leukemia; cytotoxicity; indole alkaloids; mitochondrial pathway