Comprehensive Overview of β-Methoxyacrylate Derivatives as Cytochrome bc₁ Inhibitors for Novel Pesticide Discovery

Abstract

β-Methoxyacrylate derivatives represent a new class of pesticides, which have attracted increasing attention owing to their unique structure, broad biological activity, and unique mechanisms of action. They inhibit mitochondrial respiration via preventing electron transfer at the Qo site of the cytochrome bc 1 complex and thus are identified as cyt bc 1 inhibitors. A variety of βmethoxyacrylate derivatives have been reported by many research groups for discovery of novel pesticides with improved expected activities. This review focuses on development of β-methoxyacrylate derivatives with great significance as pesticides such as fungicides, acaricides, insecticides, herbicides, and antiviral agents. In addition, the structure−activity relationships (SARs) of βmethoxyacrylate derivatives are summarized. Moreover, the cause of resistance to β-methoxyacrylate fungicides and some solutions are also introduced. Finally, the development trend of β-methoxyacrylate derivatives as pesticides is explored. We hope the review will give a guide to develop novel β-methoxyacrylate pesticides in the future.

Discovery of Novel Pyrazole Acyl Thiourea Skeleton Analogue as Potential Herbicide Candidates

“…Rational molecular design approaches in pharmaceutical and agrochemical studies, in conjunction with structure–activity relationship studies, can facilitate lead scaffold optimization, thereby enabling the development of novel compounds with intellectual property rights. Among them, common strategies include bioisostere replacement, scaffold hopping, pro-pesticide strategy, intermediate derivatization, computer-aided drug design, − and others. − For example, various types of strobilurin pharmacophores were discovered based on the β-methoxyacrylate structure, employing bioisosterism principles . The novel herbicide tetflupyrolimet, which targets dihydroorotate dehydrogenase (DHODH) was derived from scaffold hopping .…”

“…23−25 For example, various types of strobilurin pharmacophores were discovered based on the β-methoxyacrylate structure, employing bioisosterism principles. 26 The novel herbicide tetflupyrolimet, which targets dihydroorotate dehydrogenase (DHODH) was derived from scaffold hopping. 23 Pro-pesticides such as pyrazolinate, pyrazoxyfen, and benzofenap underwent in vivo metabolization, transforming into biologically active 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) inhibitors.…”

Novel Pyrazole-4-Carboxamide Derivatives Containing Oxime Ether Group as Potential SDHIs to Control Rhizoctonia solani

“…11 Pyraclostrobin (depicted in Figure 1), a QoI fungicide that possesses a pyrazole ring, has gained immense popularity as one of the most extensively utilized and highest-selling agricultural fungicides since its launch into the market in 2003, and the widespread sales of pyraclostrobin have played a pivotal role in advancing the market growth of chemical fungicides. 23 Oxathiapiprolin (Figure 1), another approved fungicide bearing a pyrazole ring and with a novel mode of action, exhibits remarkable antifungal efficacy against various crop diseases such as downy mildew and late blight. 24 Oximes are a nitrogen-containing functional group that are abundant in plant metabolites and serve as precursors to the synthesis of oxime ethers and oxime esters.…”

Bioactivity-Guided Subtraction of MIQOX for Easily Available Isoquinoline Hydrazides as Novel Antifungal Candidates

“…Inspired by the physiological importance of coenzyme Q (ubiquinone-ubiquinol) in the electron transport chain, its binding pocket and related electron-transport process have initiated increasing attention in the discovery of new pharmaceutically important molecules . Great success has been achieved especially in the innovation of fungicides for crop protection, exemplified by the commercially available succinate dehydrogenase inhibitors (SDHIs) and quinone outside inhibitors (QoIs) fungicides. − According to FRAC, SDHI fungicides showed medium to high risk in resistance management over the past several decades. − The discovery of novel and easily available models or leads with promising antifungal potentials is highly desirable.…”