Novel Thiazole Phenoxypyridine Derivatives Protect Maize from Residual Pesticide Injury Caused by PPO-Inhibitor Fomesafen

Abstract

The herbicide fomesafen has the advantages of low toxicity and high selectivity, and the target of this compound is protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4). However, this herbicide has a long residual period and can have phytotoxic effects on succeeding crops. To protect maize from fomesafen, a series of thiazole phenoxypyridines were designed based on structure–activity relationships, active substructure combinations, and bioisosterism. Bioassays showed that thiazole phenoxypyridines could improve maize tolerance under fomesafen toxicity stress to varying degrees at a dose of 10 mg·kg−1. Compound 4i exhibited the best effects. After being treated by compound 4i, average recovery rates of growth index exceeded 72%, glutathione content markedly increased by 167% and glutathione S-transferase activity was almost 163% of fomesafen-treated group. More importantly, after being treated by compound 4i, the activity of PPO, the main target enzyme of fomesafen, recovered to 93% of the control level. The molecular docking result exhibited that the compound 4i could compete with fomesafen to bind with the herbicide target enzyme, which consequently attained the herbicide detoxification. The present work suggests that compound 4i could be developed as a potential safener to protect maize from fomesafen.

Pharmacological SARM1 inhibition protects axon structure and function in paclitaxel-induced peripheral neuropathy

“…The isothiazole motif is present in a number of pharmacological agents that include kinase inhibitors, 24 antivirals, 25 herbicides and fungicides 26 , 27 and others. 28 Based on the reported mechanism of action of this class of compounds against other targets, which involves covalent modification of cysteine residues to form a disulphide adduct, 29 , 30 we investigated the possibility that these may inhibit SARM1 through a similar mechanism.…”

Research Progress in the Design and Synthesis of Herbicide Safeners: A Review

“…The diphenyl ether group was removed and substituted by Zhao et al through a bioisosteric strategy. 82 Furilazole is a wellestablished safener with good biological activity, among which the oxazolidine group may have good safener activity. According to bioelectronic properties, thiazolidine and isosteric oxazolidine may have similar activities.…”

Design, Synthesis, and Herbicidal Activity of Diphenyl Ether Derivatives Containing a Five-Membered Heterocycle

“…28,36 First, bioisosterism design is very important in the search for bioactive materials, and it has been continuously used in the development of novel herbicides. 37 In addition, substructure splicing is a common means for inventing new drugs. 38 Therefore, in this article, the pyridine ring is first used to replace one of the benzene rings in the diphenyl ether through bioisosterism design, and then the oxime ester and fivemembered heterocyclic ring are linked through substructure splicing.…”

“…First, bioisosterism design is very important in the search for bioactive materials, and it has been continuously used in the development of novel herbicides . In addition, substructure splicing is a common means for inventing new drugs .…”