Reduction and anticancer activity of platinum(IV) complexes

被引：253

作者：

Choi, S ^{[1
]}

Filotto, C ^{[1
]}

Bisanzo, M ^{[1
]}

Delaney, S ^{[1
]}

Lagasee, D ^{[1
]}

Whitworth, JL ^{[1
]}

Jusko, A ^{[1
]}

Li, CR ^{[1
]}

Wood, NA ^{[1
]}

Willingham, J ^{[1
]}

Schwenker, A ^{[1
]}

Spaulding, K ^{[1
]}

机构：

[1] Middlebury Coll, Dept Chem & Biochem, Middlebury, VT 05753 USA

来源：

INORGANIC CHEMISTRY | 1998年 / 37卷 / 10期

关键词：

D O I：

10.1021/ic971047x

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

A series of pt(IV) anticancer complexes with chloro leaving groups have been investigated for the effects of axial and carrier ligands on the reduction and cytotoxicity. The reduction rates of the Pt-IV complexes such as Pt(d,l)-(1,2-(NH2)(2)C6H10)Cl-4 (tetraplatin, Pt(dach)Cl-4; dach=diaminocyclohexane), cis,trans,cis-[Pt((CH3)(2)CHNH2)(2)(OH)(2)-Cl-2] (iproplatin, Pt(ipa)(OH)(2)Cl-2; ipa=isopropylamine), cis,trans,cis-[Pt(NH3)(CaH11NH2)(OCOCH3)(2)Cl-2] (JM-216, Pr(a,cha)(OCOCH3)(2)Cl-2.; a=ammine, cha=cyclohexylamine), cis,trans,cis-[Pt(NH3)(C6H11NH2)(OCOC3H7)(2)Cl-2] (JM-221, Pt(a,cha)(OCOC3H7)(2)Cl-2), cis,trans,cis-[Pt(en)(OH)(2)Cl-2], Pt(en)Cl-4 (en=ethylenediamine), cis,trans,cis-[Pt(en)(OCOCF3)(2)Cl-2], and cis,trans,cis-[Pt(en)(OCOCF3)(2)Cl-2] by ascorbate and cathodic reduction potentials strongly depend on the electron-withdrawing power and the steric hindrance of the axial and carrier ligands. Beginning with Pt-IV complexes bearing en carrier ligands, reduction races and reduction potentials increase in the following order of axial ligand substitutions: OH < OCOCH3 < Cl < OCOCF3, coinciding with increasing electron-withdrawing power of the axial ligand. Pt-IV complexes with en carrier ligands tend to show slower reduction rates than the corresponding complexes with ipa or cha carrier ligands. Ascorbic acid does not reduce Pt(en)(OH)(2)Cl-2, but reduces Pt(ipa)(OH)(2)Cl-2. The reduction rate of Pt(a,cha)(OCOCH3)(2)Cl-2 is about 12 times higher than that of Pt(en)(OCOCH3)(2)Cl-2. Overall, there is no strong correlation between reduction rate and cytotoxicity toward cisplatin-sensitive L1210/0 cells among the eight complexes studied. However, when the four compounds with en carrier ligands were compared with one another, the one with the fastest reduction rate exhibited the highest cytotoxicity. The cytotoxicity increases with axial ligand substitution in the order OH < OCOCH3 < Cl < OCOCF3, following the same tend as reduction rate. Comparing complexes having different carrier ligands but the same axial ligands reveals that the compound with the faster reduction rate exhibits the higher cytotoxicity. Reduction rate. and cytotoxicity increase in the order Pt(en)(OH)(2)Cl-2 < Pt(ipa)(OH)(2)Cl-2,Pt(en)(OCOCH3)(2)Cl-2 < Pt(a,cha)(OCOCH3)(3)Cl-2, Pt(en)Cl-4 < Pt(dach)Cl-4.

引用

页码：2500 / 2504

页数：5

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