title: Phosphanegold(I) dithiocarbamates, R3PAu[SC(=S)N((i)Pr)CH2CH2OH] for R = Ph, Cy and Et: role of phosphane-bound R substituents upon in vitro cytotoxicity against MCF-7R breast cancer cells and cell death pathways.
abstract: The synthesis and characterisation of R3PAu[S2CN((i)Pr)CH2CH2OH], for R = Ph (1), Cy (2) and Et (3)4, is reported. Compounds 1-3 are cytotoxic against the doxorubicin-resistant breast cancer cell line, MCF-7R, with 1 exhibiting greater potency and cytotoxicity than either of doxorubicin and cisplatin. Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis by 1, and necrosis by 2 and 3, are demonstrated, by both extrinsic and intrinsic pathways. Compound 1 activates the p53 gene, 2 activates only the p73 gene, whereas 3 activates both the p53 and p73 genes. Compounds 1 and 3 activate NF-κB, and each inhibits topoisomerase I.
authors.affiliation: Department of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Nazzatush Shimar
authors.initials: NS
authors.lastname: Jamaludin
authors.forename: Zheng-Jie
authors.initials: ZJ
authors.lastname: Goh
authors.forename: Yoke Kqueen
authors.initials: YK
authors.lastname: Cheah
authors.forename: Kok-Pian
authors.initials: KP
authors.lastname: Ang
authors.forename: Jiun Horng
authors.initials: JH
authors.lastname: Sim
authors.forename: Chai Hoon
authors.initials: CH
authors.lastname: Khoo
authors.forename: Zainal Abidin
authors.initials: ZA
authors.lastname: Fairuz
authors.forename: Siti Nadiah Binti Abdul
authors.initials: SN
authors.lastname: Halim
authors.forename: Seik Weng
authors.initials: SW
authors.lastname: Ng
authors.forename: Hoi-Ling
authors.initials: HL
authors.lastname: Seng
authors.forename: Edward R T
authors.initials: ER
authors.lastname: Tiekink
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D050607:Organogold Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010720:Phosphines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D050607:Organogold Compounds; D010720:Phosphines; D013859:Thiocarbamates; C044646:phosphine
keywords: Cancer; Cell cycle; Chrysotherapy; Dithiocarbamate; Gold(I) complexes; Metallopharmaceuticals