title: Isoquinoline derivatives Zn(II)/Ni(II) complexes: Crystal structures, cytotoxicity, and their action mechanism.
abstract: Three transition metal complexes with isoquinoline derivatives: [(MPDQ)2Zn(C2H5OH)ClO4]ClO4 (1) (MPDQ = 4,5-methylenedioxy-1-pyridinedihydroisoquinoline), [(PYP)2Zn(H2O)](ClO4)2 (2) (PYP = 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline) and [(MPDQ)2Ni(CH3OH)ClO4]ClO4 (3) were synthesized and fully characterized. All complexes exhibited strong proliferation inhibition activity against various tested cancer cells with high selectivity to tumour and normal cells. BEL-7404 cells were found most sensitive to complex 2 by inducing apoptosis. The process involved the mitochondrial membrane potential depolarization, PARP-proteins cleavage, Bcl-2, p53, p21 expression and caspase family members' activation. Taking these findings into account, it can propose that complex 2 induce cancer cell apoptosis via mitochondrial pathways. The interaction of complex 2 with DNA investigated by fluorescence, CD and viscosity indicated that complex 2 interact with DNA mainly via intercalation.
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.
authors.forename: Ke-Bin
authors.initials: KB
authors.lastname: Huang
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.
authors.forename: Hui-Yan
authors.initials: HY
authors.lastname: Mo
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. Electronic address: chenzf@gxnu.edu.cn.
authors.forename: Zhen-Feng
authors.initials: ZF
authors.lastname: Chen
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.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Wei
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.
authors.forename: Yan-Cheng
authors.initials: YC
authors.lastname: Liu
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. Electronic address: hliang@gxnu.edu.cn.
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; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D009532:Nickel / Q000737:chemistry / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D015032:Zinc / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007546:Isoquinolines; D009942:Organometallic Compounds; D009532:Nickel; D015032:Zinc; C039109:isoquinoline
keywords: Crystal structure; Cytotoxicity; Isoquinoline derivatives; Mitochondria-mediated apoptosis; Zn(II)/Ni(II) complexes