title: Synthesis and antitumor activities of novel rhein α-aminophosphonates conjugates.
abstract: Several rhein α-aminophosphonates conjugates (5a-5q) were synthesized and evaluated for in vitro cytotoxicity against HepG-2, CNE, Spca-2, Hela and Hct-116 cell lines. Some compounds showed relatively high cytotoxicity. Especially, compound 5i exhibited the strongest cytotoxicity against Hct-116 cells (IC50 was 5.32 μM). All the synthesized compounds exhibited low cytotoxicity against HUVEC cells. The mechanism of compound 5i was preliminarily investigated by Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which indicated that the compound 5i induced apoptosis in Hct-116 cancer cells. Cell cycle analysis showed that these compound 5i mainly arrested Hct-116 cells in G1 stage. The effects of 5i on the activation of caspases expression indicated that 5i might induce apoptosis via the membrane death receptor pathways. In addition, the binding properties of a model analog 5i to DNA were investigated by methods (UV-vis, fluorescence, CD spectroscopy and FRET-melting) in compare with that of rhein. Results indicated that 5i showed moderate ability to interact ct-DNA.
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Science of Guangxi Normal University, Guilin 541004, PR China; Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China.
authors.forename: Gui-yang
authors.initials: GY
authors.lastname: Yao
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Science of Guangxi Normal University, Guilin 541004, PR China.
authors.forename: Man-yi
authors.initials: MY
authors.lastname: Ye
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Science of Guangxi Normal University, Guilin 541004, PR China.
authors.forename: Ri-zhen
authors.initials: RZ
authors.lastname: Huang
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Science of Guangxi Normal University, Guilin 541004, PR China.
authors.forename: Ya-jun
authors.initials: YJ
authors.lastname: Li
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Science of Guangxi Normal University, Guilin 541004, PR China.
authors.forename: Ying-ming
authors.initials: YM
authors.lastname: Pan
authors.affiliation: College of Pharmacy, Guilin Medical University, Guilin 541004, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutical Engineering, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China. Electronic address: zxliao@seu.edu.cn.
authors.forename: Zhi-xin
authors.initials: ZX
authors.lastname: Liao
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry & Pharmaceutical Science of Guangxi Normal University, Guilin 541004, PR China. Electronic address: whengshan@163.com.
authors.forename: Heng-shan
authors.initials: HS
authors.lastname: Wang
mesh_terms: D000880:Anthraquinones / Q000138:chemical synthesis* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000502:physiology; D045325:HCT116 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; D063065:Organophosphonates; C020491:rhein
keywords: Apoptosis; Cytotoxicity; DNA binding; Rhein; Synthesis; α-Aminophosphonates