Discovery, mode of action, resistance mechanisms, and plan of action for sustainable use of Group 14 herbicides

Abstract

Protoporphyrinogen oxidase (PPO) inhibiting herbicides remain an important and useful chemistry 60 years after their first introduction. In this review, based on topics introduced at the WSSA 2021 symposium titled “A History, Overview, and Plan of Action on PPO Inhibiting Herbicides”, we discuss the current state of PPO inhibiting herbicides. Renewed interest in the PPO inhibiting herbicides in recent years, due to increased use and increased resistance cases, has led to refinements in knowledge regarding the mechanism of action of PPO inhibitors. Herein we discuss the importance of the two isoforms of PPO in plants, compile a current knowledge of target site resistance mechanisms, discuss non target site resistance cases and review crop selectivity mechanisms. To effectively study and compare PPO inhibitor resistance cases, consistent and reproducible greenhouse screening and target site mutation assays are necessary. To this end we cover best practices in screening to accurately identify resistance ratios and properly interpret common screens for point mutations. The future of effective and sustainable PPO inhibitor use relies on development of new chemistries that maintain activity on resistant biotypes and the promotion of responsible stewardship of PPO inhibitors both new and old. We present the biorational design of the new PPO inhibitor trifludimoxazin to highlight the future of PPO inhibitor development and discuss the elements of sustainable weed control programs using PPO inhibitors as well as how responsible stewardship can be incentivized. The sustained use of PPO inhibitors in future agriculture relies on the effective and timely communication from mode of action and resistance research to agronomists, extension workers, and farmers themselves.

Molecular Targets of Herbicides and Fungicides─Are There Useful Overlaps for Fungicide Discovery?

“…PPO is also essential for chlorophyll synthesis, and 22 commercial herbicides from six chemical groups (HRAC group 14) inhibit this enzyme. In plants, high levels of ProtoIX accumulate outside the plastid when PPO is inhibited. , ProtoIX is a photosensitizer, producing high levels of reactive oxygen species (ROS) in the presence of light and molecular oxygen. PPO inhibitor herbicides act more rapidly than almost all other herbicides because of this mechanism of action.…”

Design, Synthesis, and Biological Activity of Novel Phenyltriazolinone PPO Inhibitors Containing Five-Membered Heterocycles

“…Among them, chemical weeding still plays an important role in increasing crop yield. , For example, the use of herbicides with different modes of action can damage 90–99% of target weeds, which is also the most effective weed control method at present. However, the long-term use and abuse of herbicides will cause environmental pollution and pose potential risks to human health. − At the same time, weed species that are resistant to herbicide-active ingredients are also increasing year by year, which has become a problem that cannot be ignored. − Therefore, it is necessary to develop new environmentally friendly herbicides with high activity, low dose, broad spectrum, and low toxicity.…”

Synthesis and Biological Activity Evaluation of Benzoxazinone-Pyrimidinedione Hybrids as Potent Protoporphyrinogen IX Oxidase Inhibitor

“…This lack of bioselectivity has led to a range of neurological and dermatological issues . As a result, the research and development (R&D) of bioselective PPO inhibitors have been considered a pivotal scientific research direction in the global pesticide field in recent years. , …”

“…25 As a result, the research and development (R&D) of bioselective PPO inhibitors have been considered a pivotal scientific research direction in the global pesticide field in recent years. 26,27 To date, approximately 30 PPO inhibitors have been commercialized to control weeds in fields. Based on their structural features, PPO-inhibiting herbicides can be classified into four types: diphenyl ethers, N-phenyl-imides, N-phenyltriazolinones, and N-phenyl-oxadiazolones (Figure 1).…”