Characterization of Oxygenated Propenylbenzene Derivatives Binding to MAO-A Using Isothermal Titration Calorimetry and Molecular Modeling

Monoamine oxidase A (MAO-A) is the main enzyme that deaminates serotonin. Correct serotonin concentration regulates appetite, improves well-being, reduces symptoms of depression, but also improves memory and heart function. In this study, the use of new compounds chemo-enzymatically synthesized from...

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Main Authors: Joanna Grzelczyk, Horacio Pérez-Sánchez, Miguel Carmena-Bargueño, Ilona Gałązka-Czarnecka, Grażyna Budryn, Dawid Hernik, Elisabetta Brenna, Filip Boratyński
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Applied Sciences
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Online Access:https://www.mdpi.com/2076-3417/14/23/10856
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author Joanna Grzelczyk
Horacio Pérez-Sánchez
Miguel Carmena-Bargueño
Ilona Gałązka-Czarnecka
Grażyna Budryn
Dawid Hernik
Elisabetta Brenna
Filip Boratyński
author_facet Joanna Grzelczyk
Horacio Pérez-Sánchez
Miguel Carmena-Bargueño
Ilona Gałązka-Czarnecka
Grażyna Budryn
Dawid Hernik
Elisabetta Brenna
Filip Boratyński
author_sort Joanna Grzelczyk
collection DOAJ
description Monoamine oxidase A (MAO-A) is the main enzyme that deaminates serotonin. Correct serotonin concentration regulates appetite, improves well-being, reduces symptoms of depression, but also improves memory and heart function. In this study, the use of new compounds chemo-enzymatically synthesized from propenylbenzene derivatives as MAO-A inhibitors was proposed. Isothermal titration calorimetry analysis and molecular modeling were used to determine the inhibitory effect of MAO-A. The main compounds such as propenylbenzenes were observed to have no inhibitory effect. However, in the case of diols and hydroxy ketones, the compounds showed MAO-A inhibitory effects. In particular, 1-(4-hydroxy-3-methoxyphenyl)propane-1,2-diol, both in isothermal titration calorimetry (ITC) and molecular modeling, showed high affinity for the MAO-A enzyme, thus protecting serotonin from deamination. The results suggest that propenylbenzene derivatives, such as diols and hydroxy ketones, bind to MAO-A at the active site. This suggests their potential to be used as drugs or food supplements to prevent depression. These studies may constitute a new tool for further in vivo and in vitro studies.
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institution Kabale University
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spelling doaj-art-0c6cec98f8434285acbdcf64844072f72024-12-13T16:21:57ZengMDPI AGApplied Sciences2076-34172024-11-0114231085610.3390/app142310856Characterization of Oxygenated Propenylbenzene Derivatives Binding to MAO-A Using Isothermal Titration Calorimetry and Molecular ModelingJoanna Grzelczyk0Horacio Pérez-Sánchez1Miguel Carmena-Bargueño2Ilona Gałązka-Czarnecka3Grażyna Budryn4Dawid Hernik5Elisabetta Brenna6Filip Boratyński7Institute of Food Technology and Analysis, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, 90-537 Lodz, PolandStructural Bioinformatics and High-Performance Computing Research Group (BIO-HPC), Computer Engineering Department, Universidad Católica de Murcia (UCAM), Guadalupe, 30107 Murcia, SpainStructural Bioinformatics and High-Performance Computing Research Group (BIO-HPC), Computer Engineering Department, Universidad Católica de Murcia (UCAM), Guadalupe, 30107 Murcia, SpainInstitute of Food Technology and Analysis, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, 90-537 Lodz, PolandInstitute of Food Technology and Analysis, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, 90-537 Lodz, PolandDepartment of Food Chemistry and Biocatalysis, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, PolandDipartimento di Chimica, Materiali ed Ingegneria Chimica “Giulio Natta”, Politecnico di Milano, I-20133 Milan, ItalyDepartment of Food Chemistry and Biocatalysis, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, PolandMonoamine oxidase A (MAO-A) is the main enzyme that deaminates serotonin. Correct serotonin concentration regulates appetite, improves well-being, reduces symptoms of depression, but also improves memory and heart function. In this study, the use of new compounds chemo-enzymatically synthesized from propenylbenzene derivatives as MAO-A inhibitors was proposed. Isothermal titration calorimetry analysis and molecular modeling were used to determine the inhibitory effect of MAO-A. The main compounds such as propenylbenzenes were observed to have no inhibitory effect. However, in the case of diols and hydroxy ketones, the compounds showed MAO-A inhibitory effects. In particular, 1-(4-hydroxy-3-methoxyphenyl)propane-1,2-diol, both in isothermal titration calorimetry (ITC) and molecular modeling, showed high affinity for the MAO-A enzyme, thus protecting serotonin from deamination. The results suggest that propenylbenzene derivatives, such as diols and hydroxy ketones, bind to MAO-A at the active site. This suggests their potential to be used as drugs or food supplements to prevent depression. These studies may constitute a new tool for further in vivo and in vitro studies.https://www.mdpi.com/2076-3417/14/23/10856MAO-Aserotonindocking simulationpropenylbenzenesisothermal titration calorimetry
spellingShingle Joanna Grzelczyk
Horacio Pérez-Sánchez
Miguel Carmena-Bargueño
Ilona Gałązka-Czarnecka
Grażyna Budryn
Dawid Hernik
Elisabetta Brenna
Filip Boratyński
Characterization of Oxygenated Propenylbenzene Derivatives Binding to MAO-A Using Isothermal Titration Calorimetry and Molecular Modeling
Applied Sciences
MAO-A
serotonin
docking simulation
propenylbenzenes
isothermal titration calorimetry
title Characterization of Oxygenated Propenylbenzene Derivatives Binding to MAO-A Using Isothermal Titration Calorimetry and Molecular Modeling
title_full Characterization of Oxygenated Propenylbenzene Derivatives Binding to MAO-A Using Isothermal Titration Calorimetry and Molecular Modeling
title_fullStr Characterization of Oxygenated Propenylbenzene Derivatives Binding to MAO-A Using Isothermal Titration Calorimetry and Molecular Modeling
title_full_unstemmed Characterization of Oxygenated Propenylbenzene Derivatives Binding to MAO-A Using Isothermal Titration Calorimetry and Molecular Modeling
title_short Characterization of Oxygenated Propenylbenzene Derivatives Binding to MAO-A Using Isothermal Titration Calorimetry and Molecular Modeling
title_sort characterization of oxygenated propenylbenzene derivatives binding to mao a using isothermal titration calorimetry and molecular modeling
topic MAO-A
serotonin
docking simulation
propenylbenzenes
isothermal titration calorimetry
url https://www.mdpi.com/2076-3417/14/23/10856
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