Optimization of important early ADME(T) parameters of NADPH oxidase-4 inhibitor molecules
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2012 |
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| Erschienen: |
2012 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
|---|---|
| Enthalten in: |
Medicinal chemistry (Shariqah (United Arab Emirates)) - 8(2012), 2 vom: 28. März, Seite 174-81 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Borbély, Gábor [VerfasserIn] |
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| Themen: |
EC 1.6.3.- |
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| Anmerkungen: |
Date Completed 05.11.2012 Date Revised 21.10.2021 published: Print Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM215896491 |
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| 245 | 1 | 0 | |a Optimization of important early ADME(T) parameters of NADPH oxidase-4 inhibitor molecules |
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| 500 | |a Date Completed 05.11.2012 | ||
| 500 | |a Date Revised 21.10.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Enzyme Inhibitors |2 NLM | |
| 650 | 7 | |a NADPH Oxidase 4 |2 NLM | |
| 650 | 7 | |a EC 1.6.3.- |2 NLM | |
| 650 | 7 | |a NADPH Oxidases |2 NLM | |
| 650 | 7 | |a EC 1.6.3.- |2 NLM | |
| 650 | 7 | |a NOX4 protein, human |2 NLM | |
| 650 | 7 | |a EC 1.6.3.- |2 NLM | |
| 700 | 1 | |a Huszár, Ménika |e verfasserin |4 aut | |
| 700 | 1 | |a Varga, Attila |e verfasserin |4 aut | |
| 700 | 1 | |a Futosi, Krisztina |e verfasserin |4 aut | |
| 700 | 1 | |a Mócsai, Attila |e verfasserin |4 aut | |
| 700 | 1 | |a Orfi, László |e verfasserin |4 aut | |
| 700 | 1 | |a Idei, Miklós |e verfasserin |4 aut | |
| 700 | 1 | |a Mandl, József |e verfasserin |4 aut | |
| 700 | 1 | |a Kéri, György |e verfasserin |4 aut | |
| 700 | 1 | |a Vántus, Tibor |e verfasserin |4 aut | |
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