title: Cytotoxicity of platinum(IV) and platinum(II) complexes containing 1R,2R-cyclohexanediamine as a ligand.
abstract: Several Pt(IV) and Pt(II) complexes containing 1R,2R-cyclohexanediamine (1R,2R-dach) as a carrier ligand were synthesized. The cytotoxicities and the uptake of the platinum complexes by leukemia L1210 cells were compared in order to study the correlation between their structures and cytotoxicities. [Pt(II)Cl2(1R,2R-dach)], [(Pt(II)(oxalato)(1R,2R-dach)], and [Pt(II)(malonato)(1R,2R-dach)], which have excellent anticancer properties, exhibited very high cytotoxicities and were easily taken up by leukemia L1210 cells. [Pt(IV)Cl4(1R,2R-dach)], trans(Cl)-[Pt(IV)Cl2(oxalato)(1R,2R-dach)], and trans(Cl)-[Pt(IV)Cl2(malonato)(1R,2R-dach)] also had high cytotoxicities. After a short incubation time, the uptake of [Pt(II)Cl2(1R,2R-dach)], [Pt(II)(oxalato)(1R,2R-dach)], and [Pt(II)(malonato)(1R,2R-dach)] by leukemia L1210 cells were respectively very similar to those of [Pt(IV)Cl4(1R,2R-dach)], trans(Cl)-[Pt(IV)Cl2(oxalato)(1R,2R-dach)], and trans(Cl)-[Pt(IV)Cl2(malonato)(1R,2R-dach)]. In addition, trans(OH)-[Pt(IV)(OH)2Y2(1R,2R-dach)] (Y2: oxalato or malonato) did not exhibit cytotoxicity towards leukemia L1210 cells, whereas trans(Cl)-[Pt(IV)Cl2Y2(1R,2R-dach)] (Y2: oxalato or malonato) were highly cytotoxic. The accumulation of trans(OH)-[Pt(IV)(OH)2Y2(1R,2R-dach)] in leukemia L1210 cells was much lower than that of trans(Cl)-[Pt(IV)Cl2Y2(1R,2R-dach)]. Platinum(IV) complexes, in which leaving groups are replaced by hydroxide groups, have decreased cytotoxic activity, because the hydroxide groups of the platinum(IV) complex reduce the uptake of platinum by the cells. trans(OH),cis(Cl)-[Pt(IV)(OH)2Cl2(1R,2R-dach)], which has hydroxide and chloride groups, was easily incorporated into the cells and exhibited the high cytotoxic activity. This behavior indicates that the chloride group apparently overcomes the ameliorating effect of the hydroxide group.
authors.affiliation: Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: J
authors.initials: J
authors.lastname: Hirose
authors.forename: M
authors.initials: M
authors.lastname: Noji
authors.forename: R
authors.initials: R
authors.lastname: Saito
authors.forename: H
authors.initials: H
authors.lastname: Tomida
authors.forename: Y
authors.initials: Y
authors.lastname: Kidani
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D003514:Cyclohexylamines / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D007939:Leukemia L1210 / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D003514:Cyclohexylamines; D009944:Organoplatinum Compounds; D004247:DNA; C030435:1,2-cyclohexanediamine