Optimization of important early ADME(T) parameters of NADPH oxidase-4 inhibitor molecules

Gábor Borbély, Mónika Huszár, Attila Varga, Krisztina Futosi, Attila Mócsai, László Orfi, Miklós Idei, József Mandl, György Kéri, Tibor Vántus

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Through their reactive oxygen species (ROS) producing function, NADPH oxidase (NOX) enzymes have been linked to several oxidative stress related diseases. In our recently published paper [1] we have already shown the NOX4 inhibitory effect of diverse, molecule sub-libraries and their biological importance. We also presented our work connected to potential anti-tumour molecules and the relationship between their biological activity and physico-chemical properties [2]. As an extension of these studies further physico-chemical and biological investigation has been carried out on a molecule group included NOX4 inhibitory chromanone compounds. Here we describe the optimization of early ADME(T) parameters determining lipophilicity, phospholipophilicity and permeability linked to structure-activity relationship. We prove that optimal lipo-and phospholipophilicty can be also determined in case of NOX4 inhibitors and a comparison will be made between the chemically similar isochromanone and chromanone molecular libraries. It will be also shown how to predict the effect of different substituents on permeability, lipo-and phospholipophilicity and also the biological differences between anti-tumour molecules and NOX4 inhibitors according to their penetration ability.

Original languageEnglish
Pages (from-to)174-181
Number of pages8
JournalMedicinal Chemistry
Volume8
Issue number2
DOIs
Publication statusPublished - Mar 2012

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Keywords

  • ADME(T)
  • Characterization
  • Compounds
  • Disease
  • Inhibitor
  • NADPH oxidase 4
  • Relationship

ASJC Scopus subject areas

  • Drug Discovery

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