title: Design, synthesis and biological evaluation of novel 1-hydroxyl-3-aminoalkoxy xanthone derivatives as potent anticancer agents.
abstract: A series of novel 1-hydroxyl-3-aminoalkoxy xanthone derivatives were designed, synthesized and evaluated for in vitro anticancer activity against four selected human cancer cell lines (nasopharyngeal neoplasm CNE, liver cancer BEL-7402, gastric cancer MGC-803, lung adenocarcinoma A549). Most of the synthesized compounds exhibit effective cytotoxic activity against the four tested cancer cell lines with the IC50 values at micromolar concentration level. Some preliminary structure-activity relationships were also discussed. In this series of derivatives, compound 3g shows excellent broad spectrum anticancer activity with IC50 values ranging from 3.57 to 20.07 μM. The in vitro anticancer activity effect and action mechanism of compound 3g on human gastric carcinoma MGC-803 cell were further investigated. The results showed that compound 3g exhibits dose- and time-dependent anticancer effects on MGC-803 cells through apoptosis, which might be associated with its decreasing intracellular calcium and the mitochondrial membrane potential.
authors.affiliation: Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, PR China.
authors.forename: Zheng-Min
authors.initials: ZM
authors.lastname: Yang
authors.affiliation: Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, PR China. Electronic address: jiangkeq@sina.com.
authors.forename: Jiang-Ke
authors.initials: JK
authors.lastname: Qin
authors.affiliation: Department of Pharmacology, Guilin Medical University, Guilin 541004, PR China. Electronic address: dzhk110@126.com.
authors.forename: Zhi-Kai
authors.initials: ZK
authors.lastname: Dai
authors.affiliation: Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, PR China.
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Lan
authors.affiliation: Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, PR China.
authors.forename: Gui-Fa
authors.initials: GF
authors.lastname: Su
authors.affiliation: Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, PR China.
authors.forename: Huang
authors.initials: H
authors.lastname: Tang
authors.affiliation: Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D013329:Structure-Activity Relationship; D044004:Xanthones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D044004:Xanthones
keywords: Anticancer activity; Apoptosis; Intracellular calcium; Mitochondrial membrane potential; Structure–activity relationships; Synthesis; Xanthone