J 2021

PPO-Inhibiting Herbicides and Structurally Relevant Schiff Bases: Evaluation of Inhibitory Activities against Human Protoporphyrinogen Oxidase

JAKUBEK, Milan, Michal MASAŘÍK, Tomas BRIZA, Robert KAPLANEK, Katerina VESELA et. al.

Basic information

Original name

PPO-Inhibiting Herbicides and Structurally Relevant Schiff Bases: Evaluation of Inhibitory Activities against Human Protoporphyrinogen Oxidase

Authors

JAKUBEK, Milan (203 Czech Republic), Michal MASAŘÍK (203 Czech Republic, belonging to the institution), Tomas BRIZA (203 Czech Republic), Robert KAPLANEK (203 Czech Republic), Katerina VESELA (203 Czech Republic), Nikita ABRAMENKO and Pavel MARTASEK (203 Czech Republic)

Edition

Processes, Basel, MDPI, 2021, 2227-9717

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

20402 Chemical process engineering

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

Impact factor

Impact factor: 3.352

RIV identification code

RIV/00216224:14110/21:00121763

Organization unit

Faculty of Medicine

DOI

UT WoS

000623166400001

Keywords in English

protoporphyrinogen oxidase; inhibitors; herbicides

Tags

Tags

International impact, Reviewed
Změněno: 21/3/2022 07:54, Mgr. Tereza Miškechová

Abstract

V originále

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.