title: Synthesis, Characterization, and Anticancer Activity of Novel Lipophilic Emodin Cationic Derivatives.
abstract: Seventeen novel emodin derivatives were synthesized, and the structures were confirmed by IR, H NMR, MS, and elemental analysis. The cytotoxic activity of the derivatives was evaluated against A375, BGC-823, HepG2, and HELF cells by MTT assay. Compound 9a with highest potency and low toxicity was selected to further investigate its detailed molecular mechanism. The lead compound 9a induced a loss of the mitochondrial transmembrane potential (▵Ψm), an increase in reactive oxygen species (ROS), release of cytochrome c and activation of caspase-3 and caspase-9. In addition, the confocal study showed that emodin derivative 9a (containing asymmetric hydrocarbon tails) was mainly localized in mitochondria, demonstrating a key role of the mitochondria-mediated apoptosis pathway in cancer cells. Taken together, the results demonstrate that embodin derivative 9a preferentially regulates the ROS-mediated apoptosis in A375 cells through the induction of cytochrome c expression and activation of caspase-3 and caspase-9 proteins.
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Yang
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108, China.
authors.forename: Wenna
authors.initials: W
authors.lastname: Zhao
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108, China.
authors.forename: Xiufang
authors.initials: X
authors.lastname: Hu
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108, China.
authors.forename: Xianxiao
authors.initials: X
authors.lastname: Hao
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Hong
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108, China.
authors.forename: Jianlong
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Xiang
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108, China.
authors.forename: Yunhui
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108, China.|Research Institute of Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou, Fujian, 350002, China.
authors.forename: Yaofeng
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108, China.|Department of Pharmaceutics, University of Washington, Seattle, WA, 98105, USA.
authors.forename: Rodney J Y
authors.initials: RJ
authors.lastname: Ho
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108, China.|Research Institute of Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou, Fujian, 350002, China.
authors.forename: Wenfeng
authors.initials: W
authors.lastname: Wang
authors.affiliation: College of Chemistry, Fuzhou University, Fuzhou, Fujian, 350108, China.|Research Institute of Photocatalysis, State Key Laboratory of Photocatalysis on Energy and Environment, Fuzhou, Fujian, 350002, China.|Department of Pharmaceutics, University of Washington, Seattle, WA, 98105, USA.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Shao
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D015195:Drug Design; D004642:Emodin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D045304:Cytochromes c; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D004642:Emodin
keywords: apoptosis; emodin derivative; reactive oxygen species; synthesis