title: Synthesis, SAR and pharmacological characterization of novel anthraquinone cation compounds as potential anticancer agents.
abstract: Emodin, a natural anthraquinone derivative isolated from Rheum palmatum L., has been demonstrated to exhibit good anti-cancer effect. In this study, a series of novel quaternary ammonium salts of emodin, anthraquinone and anthrone were synthesized and their anticancer activities were tested in vitro. The effects of emodin quaternary ammonium salts on cell viability, apoptosis, intracellular ROS, and mitochondrial membrane potential were investigated in A375, BGC-823, HepG2 and HELF cells. The results demonstrated that compound 4a induced morphological changes and decreased cell viability. Apoptosis triggered by compound 4a was visualized using DAPI staining and Annexin V-FITC/PI staining. Compound 4a-induced apoptosis of A375 cells were showed to be associated with the dissipation of mitochondrial membrane potential (ΔΨm) as a result of the up-regulation of P53 and Caspase-3. When cancer cells were treated with emodin derivative, their ability to generate reactive oxygen species (ROS) rose significantly and the mitochondrial membrane potential decreased. Additionally, confocal microscopy assay confirmed that compound 4a was primarily located in the mitochondria of A375 cells. These results suggested that compound 4a has the potential for use in cancer therapy.
authors: College of Chemistry, Fuzhou University, 350108, PR China.
authors: Yanyan
authors: Y
authors: Zheng
authors: College of Chemistry, Fuzhou University, 350108, PR China.
authors: Li
authors: L
authors: Zhu
authors: College of Chemistry, Fuzhou University, 350108, PR China.
authors: Lulu
authors: L
authors: Fan
authors: College of Chemistry, Fuzhou University, 350108, PR China.
authors: Wenna
authors: W
authors: Zhao
authors: College of Chemistry, Fuzhou University, 350108, PR China.
authors: Jianlong
authors: J
authors: Wang
authors: College of Chemistry, Fuzhou University, 350108, PR China.
authors: Xianxiao
authors: X
authors: Hao
authors: College of Chemistry, Fuzhou University, 350108, PR China.
authors: Yunhui
authors: Y
authors: Zhu
authors: College of Chemistry, Fuzhou University, 350108, PR China.
authors: Xiufang
authors: X
authors: Hu
authors: College of Chemistry, Fuzhou University, 350108, PR China.
authors: Yaofeng
authors: Y
authors: Yuan
authors: College of Chemistry, Fuzhou University, 350108, PR China. Electronic address: shaojingwei@fzu.edu.cn.
authors: Jingwei
authors: J
authors: Shao
authors: College of Chemistry, Fuzhou University, 350108, PR China. Electronic address: wangwf@fzu.edu.cn.
authors: Wenfeng
authors: W
authors: Wang
mesh_terms: D000880:Anthraquinones / Q000138:chemical synthesis / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002412:Cations / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D004642:Emodin / Q000494:pharmacology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; D002412:Cations; D017382:Reactive Oxygen Species; D004642:Emodin
keywords: Anticancer activity; Quaternary ammonium salt; Quinoid structure; Reactive oxygen species; Synthesis