LAPSE:2023.24876
Published Article
LAPSE:2023.24876
PPO-Inhibiting Herbicides and Structurally Relevant Schiff Bases: Evaluation of Inhibitory Activities against Human Protoporphyrinogen Oxidase
March 28, 2023
Abstract
The study of human protoporphyrinogen oxidase (hPPO) inhibition can contribute significantly to a better understanding of some pathogeneses (e.g., porphyria, herbicide exposure) and the development of anticancer agents. Therefore, we prepared new potential inhibitors with Schiff base structural motifs (2-hydroxybenzaldehyde-based Schiff bases 9−13 and chromanone derivatives 17−19) as structurally relevant to PPO herbicides. The inhibitory activities (represented by the half maximal inhibitory concentration (IC50) values) and enzymatic interactions (represented by the hPPO melting temperatures) of these synthetic compounds and commercial PPO herbicides used against hPPO were studied by a protoporphyrin IX fluorescence assay. In the case of PPO herbicides, significant hPPO inhibition and changes in melting temperature were observed for oxyfluorten, oxadiazon, lactofen, butafenacil, saflufenacil, oxadiargyl, chlornitrofen, and especially fomesafen. Nevertheless, the prepared compounds did not display significant inhibitory activity or changes in the hPPO melting temperature. However, a designed model of hPPO inhibitors based on the determined IC50 values and a docking study (by using AutoDock) found important parts of the herbicide structural motif for hPPO inhibition. This model could be used to better predict PPO herbicidal toxicity and improve the design of synthetic inhibitors.
The study of human protoporphyrinogen oxidase (hPPO) inhibition can contribute significantly to a better understanding of some pathogeneses (e.g., porphyria, herbicide exposure) and the development of anticancer agents. Therefore, we prepared new potential inhibitors with Schiff base structural motifs (2-hydroxybenzaldehyde-based Schiff bases 9−13 and chromanone derivatives 17−19) as structurally relevant to PPO herbicides. The inhibitory activities (represented by the half maximal inhibitory concentration (IC50) values) and enzymatic interactions (represented by the hPPO melting temperatures) of these synthetic compounds and commercial PPO herbicides used against hPPO were studied by a protoporphyrin IX fluorescence assay. In the case of PPO herbicides, significant hPPO inhibition and changes in melting temperature were observed for oxyfluorten, oxadiazon, lactofen, butafenacil, saflufenacil, oxadiargyl, chlornitrofen, and especially fomesafen. Nevertheless, the prepared compounds did not display significant inhibitory activity or changes in the hPPO melting temperature. However, a designed model of hPPO inhibitors based on the determined IC50 values and a docking study (by using AutoDock) found important parts of the herbicide structural motif for hPPO inhibition. This model could be used to better predict PPO herbicidal toxicity and improve the design of synthetic inhibitors.
Record ID
Keywords
herbicides, inhibitors, protoporphyrinogen oxidase
Suggested Citation
Jakubek M, Masařík M, Bříza T, Kaplánek R, Veselá K, Abramenko N, Martásek P. PPO-Inhibiting Herbicides and Structurally Relevant Schiff Bases: Evaluation of Inhibitory Activities against Human Protoporphyrinogen Oxidase. (2023). LAPSE:2023.24876
Author Affiliations
Jakubek M: Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic; BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czec [ORCID]
Masařík M: Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic; BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czec
Bříza T: Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic; BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czec
Kaplánek R: Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic; BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czec [ORCID]
Veselá K: Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic; BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czec
Abramenko N: Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic [ORCID]
Martásek P: Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic
Masařík M: Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic; BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czec
Bříza T: Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic; BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czec
Kaplánek R: Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic; BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czec [ORCID]
Veselá K: Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic; BIOCEV, First Faculty of Medicine, Charles University, 252 50 Vestec, Czec
Abramenko N: Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic [ORCID]
Martásek P: Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, 121 08 Prague, Czech Republic
Journal Name
Processes
Volume
9
Issue
2
First Page
383
Year
2021
Publication Date
2021-02-19
ISSN
2227-9717
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PII: pr9020383, Publication Type: Journal Article
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LAPSE:2023.24876
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https://doi.org/10.3390/pr9020383
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Mar 28, 2023
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