title: Synthesis and biological evaluation of disubstituted amidoxanthones as potential telomeric G-quadruplex DNA-binding and apoptosis-inducing agents.
abstract: A series of disubstituted xanthones was obtained by cationic modification of xanthone's C2 and C7 with amine groups of different pKa values. Modified structures by using moieties with high pKa values had good antitumor activity according to the MTT assay, AO/EB staining and flow cytometry assay, especially bis-dimethylamine derivative (5a). Further study indicated that compound 5a had good binding activity to telomeric G-quadruplex DNA, as detected by using spectroscopy methods, melting profiles, polymerase chain reaction stop assay and molecular modeling study. The results suggested that the antitumor activity of 5a might be associated with its stabilization of G-quadruplex DNA, which could be developed as new G-quadruplex DNA stabilizer and potent antitumor agents.
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding 071002, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Shen
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding 071002, People's Republic of China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding 071002, People's Republic of China.
authors.forename: Ziqian
authors.initials: Z
authors.lastname: Li
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding 071002, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Qi
authors.affiliation: College of Pharmaceutical Sciences, Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Hebei University, Baoding 071002, People's Republic of China.
authors.forename: Yitian
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D054856:G-Quadruplexes / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D016615:Telomere / Q000187:drug effects*; D044004:Xanthones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D044004:Xanthones; C000611507:amidoxanthone
keywords: Antitumor evaluation; Apoptosis; G-quadruplex; Xanthone