title: Synthesis and antitumor activities of novel α-aminophosphonate derivatives containing an alizarin moiety.
abstract: A series of novel α-aminophosphonate derivatives containing an alizarin moiety (6-7) was designed and synthesized as antitumor agents. MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) assay results indicated that most compounds exhibited moderate to high inhibitory activity against KB, NCI-H460, HepG 2, A549, MGC-803, Hct-116, CNE and Hela tumor cell lines. The action mechanism of representative compounds 7h, 7j and 7n were investigated by fluorescence staining assays, flow cytometric analysis and real-time polymerase chain reaction (PCR) assays, which indicated that these compounds induced apoptosis and involved G1 phase arrest by increasing the production of intracellular Ca(2+) and reactive oxygen species (ROS) and affecting associated enzymes and genes. The results demonstrated that these compounds may induce apoptosis through a mitochondrion-dependent pathway.
authors: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China.
authors: Man-Yi
authors: MY
authors: Ye
authors: Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China.
authors: Gui-Yang
authors: GY
authors: Yao
authors: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China.
authors: Ying-Ming
authors: YM
authors: Pan
authors: Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China.
authors: Zhi-Xin
authors: ZX
authors: Liao
authors: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China; Department of Chemistry & Pharmaceutical Science, Guilin Normal College, Xinyi Road 15, Guangxi 541001, PR China. Electronic address: zhangye81@126.com.
authors: Ye
authors: Y
authors: Zhang
authors: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Science of Guangxi Normal University, Yucai Road 15, Guilin 541004, Guangxi, PR China. Electronic address: whengshan@163.com.
authors: Heng-Shan
authors: HS
authors: Wang
mesh_terms: D000880:Anthraquinones / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010710:Phosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; D010710:Phosphates; D017382:Reactive Oxygen Species; C010078:alizarin; D020169:Caspases; D002118:Calcium
keywords: Alizarin; Apoptosis; Cytotoxicity; Mitochondrial pathway; α-Aminophosphonate