Synthesis and analysis of the anticancer activity of platinum(II) complexes incorporating dipyridoquinoxaline variants

• Published in: Dalton transactions : an international journal of inorganic chemistry 2014-11, Vol.43 (41), p.15566-15575
• Main Authors: Pages, Benjamin J, Li, Feng, Wormell, Paul, Ang, Dale L, Clegg, Jack K, Kepert, Cameron J, Spare, Lawson K, Danchaiwijit, Supawich, Aldrich-Wright, Janice R
• Format: Article
• Language: English
• Subjects: Affinity; Animals; Anticancer properties; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Binding; Biotechnology; Cattle; Cell Line, Tumor; Crystal structure; Crystallography, X-Ray; Cyclohexylamines - chemical synthesis; Cyclohexylamines - chemistry; Cyclohexylamines - pharmacology; Deoxyribonucleic acid; Displacement; DNA - metabolism; Humans; Intercalating Agents - chemical synthesis; Intercalating Agents - chemistry; Intercalating Agents - pharmacology; Models, Molecular; Neoplasms - drug therapy; Organoplatinum Compounds - chemical synthesis; Organoplatinum Compounds - chemistry; Organoplatinum Compounds - pharmacology; Quinoxalines - chemical synthesis; Quinoxalines - chemistry; Quinoxalines - pharmacology; X-rays
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/c4dt02133a

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.