title: Structure-activity relationship of new trans-platinum(II) and (IV) complexes with cyclohexylamine. Interference with cell cycle progression and induction of cell death.
abstract: The new trans-Pt complexes, derived from trans-[PtCl2(amine)(dimethylamine)] and trans-[PtCl2(OH)2(amine)(dimethylamine)], were synthesized and characterized studying the structure-activity relationship and testing their antiproliferative activity. Their evaluation as cytotoxic agents towards different cancer and normal cell lines is presented. These compounds are active in a panel of tumor cell lines at low micromolar range. Compounds seems to be more active in tumoral than in normal primary human cell lines. Cytotoxic activity is closely related to the amine ligand. Cyclohexylamine ligand was the most active among the amine-ligands tested. Cytotoxic activity correlates with an increase in annexin V positive cells indicating an apoptotic effect of the compounds. Mechanistically, the antitumor activity correlates with a blockade of the cell cycle in S phase and a complete abolishment of G2/M checkpoint arrest suggesting physical interaction of compound with DNA inhibiting S phase transition.
authors.affiliation: Departamento de Química Inorgánica, Facultad de Ciencias, Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: González-Vadillo
authors.forename: Amparo
authors.initials: A
authors.lastname: Alvarez-Valdés
authors.forename: Victoria
authors.initials: V
authors.lastname: Moneo
authors.forename: Fernando
authors.initials: F
authors.lastname: Blanco
authors.forename: Raquel G
authors.initials: RG
authors.lastname: Díaz
authors.forename: Amancio
authors.initials: A
authors.lastname: Carnero
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro-Ranninger
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D003514:Cyclohexylamines / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology*; D010984:Platinum / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003514:Cyclohexylamines; D009942:Organometallic Compounds; D009944:Organoplatinum Compounds; C525438:dichloro(cyclohexylamine)(dimethylamine)platinum(II); C525439:dihydroxo(cyclohexylamine)(dimethylamine)platinum(II); D010984:Platinum