Journal
PROCESSES
Volume 9, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/pr9020383
Keywords
protoporphyrinogen oxidase; inhibitors; herbicides
Categories
Funding
- Czech Health Research Council [17-32727A]
- CAS [RVO: 86652036]
Ask authors/readers for more resources
The study found that some PPO herbicides showed significant inhibition of hPPO, while the newly synthesized compounds did not exhibit significant activity. However, a designed model based on determined IC50 values can 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available