title: Copper(II/I) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline: synthesis, crystal structure, antitumor activity and DNA interaction.
abstract: Three new copper(II) complexes of 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline (PYP), i.e. [Cu₂(PYP)₂Cl₄] (1), [Cu₄(PYP)₄(ClO₄)₂(H₂O)₂](ClO₄)₂·2H₂O (2), and [Cu₂(PYP)2Cl4]n (3), were synthesized and fully characterized. In comparison to free PYP, complexes 1-3 exhibited enhanced cytotoxicity against tested human tumor cell lines BEL-7404, SK-OV-3, A549, A375, MGC-803 and NCI-H460, with IC₅₀ values ranging from 0.31 to 30.76 μM. Complexes 1-3 exhibited lower cytotoxicity to HL-7702 than them to cancer cells. Complex 1 induced apoptotic death of BEL-7404, which involved mitochondria in the process. Caspase-3 activation assay indicated that 1 could be an efficient activator of caspase-3. DNA binding studies by UV-vis, DNA-melting, competitive binding, CD, viscosity measurement and agarose gel electrophoresis, revealed that intercalation might be the most likely binding mode of 1 with DNA.
authors.affiliation: Guangxi Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy of Guangxi Normal University, Guilin 541004, PR China; School of Chemistry of Nankai University, Tianjin 300071, PR China.
authors.forename: Ke-Bin
authors.initials: KB
authors.lastname: Huang
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Chen
authors.forename: Yan-Cheng
authors.initials: YC
authors.lastname: Liu
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Wei
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Xie
authors.forename: Jian-Lian
authors.initials: JL
authors.lastname: Zhang
authors.forename: Kun
authors.initials: K
authors.lastname: Hu
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D004273:DNA, Neoplasm / Q000737:chemistry / Q000187:drug effects*; D004149:Dioxoles / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C000591489:5-pyridin-2-yl-(1,3)dioxolo(4,5-g)isoquinoline; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D004149:Dioxoles; D007546:Isoquinolines; D009942:Organometallic Compounds; D003300:Copper
keywords: Copper(II) complexes; Crystal structure; Cytotoxicity; Isoquinoline; Synthesis