title: Synthesis and analysis of the anticancer activity of platinum(II) complexes incorporating dipyridoquinoxaline variants.
abstract: Eight platinum(II) complexes with anticancer potential have been synthesised and characterised. These complexes are of the type [Pt(I(L))(A(L))](2+), where I(L) is either dipyrido[3,2-f:2',3'-h]quinoxaline (dpq) or 2,3-dimethyl-dpq (23Me2dpq) and A(L) is one of the R,R or S,S isomers of either 1,2-diaminocyclohexane (SS-dach or RR-dach) or 1,2-diaminocyclopentane (SS-dacp or RR-dacp). The CT-DNA binding of these complexes and a series of other complexes were assessed using fluorescent intercalator displacement assays, resulting in unexpected trends in DNA binding affinity. The cytotoxicity of the eight synthesised compounds was determined in the L1210 cell line; the most cytotoxic of these were [Pt(dpq)(SS-dach)]Cl2 and [Pt(dpq)(RR-dach)]Cl2, with IC50 values of 0.19 and 0.80 μM, respectively. The X-ray crystal structure of the complex [Pt(dpq)(SS-dach)](ClO4)2·1.75H2O is also reported.
authors.affiliation: Nanoscale Organisation and Dynamics Group, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 2751, Australia. j.aldrich-wright@uws.edu.au.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Pages
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Paul
authors.initials: P
authors.lastname: Wormell
authors.forename: Dale L
authors.initials: DL
authors.lastname: Ang
authors.forename: Jack K
authors.initials: JK
authors.lastname: Clegg
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Kepert
authors.forename: Lawson K
authors.initials: LK
authors.lastname: Spare
authors.forename: Supawich
authors.initials: S
authors.lastname: Danchaiwijit
authors.forename: Janice R
authors.initials: JR
authors.lastname: Aldrich-Wright
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002417:Cattle; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D003514:Cyclohexylamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011810:Quinoxalines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003514:Cyclohexylamines; D007364:Intercalating Agents; D009944:Organoplatinum Compounds; D011810:Quinoxalines; D004247:DNA; C427203:calf thymus DNA; C030435:1,2-cyclohexanediamine