Intracellular targeting and pharmacological activity of the superoxide dismutase mimics MnTE-2-PyP5+ and MnTnHex-2-PyP5+ regulated by their porphyrin ring substituents.

Published

Journal Article

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-PyP(5+) and MnTnHex-2-PyP(5+), 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-PyP(5+) superior in augmenting menadione toxicity. These findings establish that both catalytic activity and intracellular distribution determine drug action.

Full Text

Duke Authors

Cited Authors

  • Aitken, JB; Shearer, EL; Giles, NM; Lai, B; Vogt, S; Reboucas, JS; Batinic-Haberle, I; Lay, PA; Giles, GI

Published Date

  • April 15, 2013

Published In

Volume / Issue

  • 52 / 8

Start / End Page

  • 4121 - 4123

PubMed ID

  • 23551184

Pubmed Central ID

  • 23551184

Electronic International Standard Serial Number (EISSN)

  • 1520-510X

Digital Object Identifier (DOI)

  • 10.1021/ic300700g

Language

  • eng

Conference Location

  • United States