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.