title: Cytotoxic platinum(II) intercalators that incorporate 1R,2R-diaminocyclopentane.
abstract: Twelve metallointercalators of the type [Pt(I(L))(A(L))](2+), where A(L) is either the R,R or S,S enantiomer of 1,2-diaminocyclopentane (DACP) and I(L) is either 1,10-phenathroline, 4-methyl-1,10-phenanthroline, 5-methyl-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 5,6-dimethyl-1,10-phenanthroline or 3,4,7,8-tetramethyl-1,10-phenanthroline, were synthesised, characterised and the cytotoxicity to the L1210 cell line was determined. The crystal structures of PHENRRDACP and PHENSS were obtained as monoclinic with a space group of P2(1) (a/Å = 11.4966, b/Å = 6.6983, c/Å = 12.0235) and P2(1) (a/Å = 11.5777, b/Å = 7.0009, c/Å = 12.5079), respectively. The R,R enantiomer of 1,2-diaminocyclopentane (RRDACP) produced the most cytotoxic metallointercalators. The most cytotoxic metallointercalators were 56MERRDACP and 47MERRDACP with IC(50) values of 0.16 and 0.17 μM, respectively, in comparison to cisplatin (1 μM).
authors.affiliation: Nanoscale Organisation and Dynamics Group, School of Science and Health, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 2751, Australia.
authors.forename: K Benjamin
authors.initials: KB
authors.lastname: Garbutcheon-Singh
authors.forename: Peter
authors.initials: P
authors.lastname: Leverett
authors.forename: Simon
authors.initials: S
authors.lastname: Myers
authors.forename: Janice R
authors.initials: JR
authors.lastname: Aldrich-Wright
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D018360:Crystallography, X-Ray; D003517:Cyclopentanes / Q000737:chemistry*; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D051379:Mice; D008968:Molecular Conformation; D010618:Phenanthrolines / Q000737:chemistry; D010984:Platinum / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D056831:Coordination Complexes; D003517:Cyclopentanes; D007364:Intercalating Agents; D010618:Phenanthrolines; C027290:3,4,7,8-tetramethyl-1,10-phenanthroline; C017518:5-methyl-1,10-phenanthroline; D010984:Platinum; C025205:1,10-phenanthroline