Intracellular Targeting and Pharmacological Activity of the Superoxide Dismutase Mimics MnTE-2-PyP5+ and MnTnHex-2-PyP5+ Regulated by Their Porphyrin Ring Substituents

被引：25

作者：

Aitken, Jade B. ^{[1
]}

Shearer, Emily L. ^{[2
]}

Giles, Niroshini M. ^{[2
]}

Lai, Barry ^{[3
]}

Vogt, Stefan ^{[3
]}

Reboucas, Julio S. ^{[4
]}

Batinic-Haberle, Ines ^{[5
]}

Lay, Peter A. ^{[1
]}

Giles, Gregory I. ^{[2
]}

机构：

[1] Univ Sydney, Sch Chem, Sydney, NSW 2006, Australia

[2] Univ Otago, Dept Pharmacol & Toxicol, Dunedin, New Zealand

[3] Argonne Natl Lab, Xray Sci Div, Argonne, IL 60439 USA

[4] Univ Fed Paraiba, Dept Quim, BR-58059900 Joao Pessoa, Paraiba, Brazil

[5] Duke Univ, Dept Radiat Oncol, Durham, NC 27710 USA

来源：

INORGANIC CHEMISTRY | 2013年 / 52卷 / 08期

关键词：

CELL-DEATH; PEROXYNITRITE; ANTIOXIDANT; CATALYSIS;

D O I：

10.1021/ic300700g

中图分类号：

O61 [无机化学];

学科分类号：

070301 [无机化学];

摘要：

Manganese porphyrin-based drugs are potent mimics of the enzyme superoxide dismutase. They exert remarkable efficacy in disease models and are entering clinical trials. Two lead compounds, MnTE-2-PyP5+ and MnTnHex-2-PyP5+, have similar catalytic rates, but differ in their alkyl chain substituents (ethyl vs n-hexyl). Herein we demonstrate that these changes in ring substitution impact upon drug intracellular distribution and pharmacological mechanism, with MnTnHex-2-PyP5+ superior in augmenting menadione toxicity. These findings establish that both catalytic activity and intracellular distribution determine drug action.

引用

收藏

页码：4121 / 4123

页数：3

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