Comprehensive Overview of Diamide Derivatives Acting as Ryanodine Receptor Activators

Abstract

The world’s hunger is continuously rising due to conflicts, climate change, pandemics (such as the recent COVID-19), and crop pests and diseases. It is widely accepted that zero hunger is impossible without using agrochemicals to control crop pests and diseases. Diamide insecticides are one of the widely used green insecticides developed in recent years and play important roles in controlling lepidopteran pests. Currently, eight diamine insecticides have been commercialized, which target the insect ryanodine receptors. This review summarizes the development and optimization processes of diamide derivatives acting as ryanodine receptor activators. The review also discusses pest resistance to diamide derivatives and possible solutions to overcome the limitations posed by the resistance. Thus, with reference to structural biology, this study provides an impetus for designing and developing diamide insecticides with improved insecticidal activities.

Discovery of Novel Diamides Scaffold Containing Monofluoro-acrylamides Activating the Insect Ryanodine Receptor

“…When R 4 were methyl and tert-butyl, the mortality of compounds B10, B12, B14, B17, B19, B22, B24, and B27 was less than 43.3%. Interestingly, the effect of the N-substituents R 4 of the amide on the biological activity was amplified when the substituents on benzene were R 2 = Cl and R 3 = Cl. For example, the activity of compound R 4 = t-butyl) was only 30% lethal at 50 mg•L −1 , while B12 (R 2 = Me, R 3 = Cl, R 4 = t-butyl) and B17 (R 2 = Me, R 3 = Br, R 4 = tbutyl) was 100%.…”

“…B11, B13, B16, B18, B21, B23, B26, and B28 with cyclopropyl and (1-cyclopropy) ethyl in R 4 exhibited excellent activity (mortality ≥90%). When R 4 were methyl and tert-butyl, the mortality of compounds B10, B12, B14, B17, B19, B22, B24, and B27 was less than 43.3%. Interestingly, the effect of the N-substituents R 4 of the amide on the biological activity was amplified when the substituents on benzene were R 2 = Cl and R 3 = Cl.…”

“…Besides, when R 2 = Me, R 3 = Br, both compounds B16 and B18 exhibited moderate activity at 1 mg• L −1 . A commonality is that these compounds exhibiting high biological activity have the structure of cycloalkane in R 4 . Thus, we fixed substituents combination on the benzene ring (R 2 = Me, R 3 = Br and R 2 = Cl, R 3 = Cl) and proceeded to investigate the influence of steric groups and synthesize compounds B29− B44 with cyclic alkanes in R 4 .…”

“…RyR in insects is very different from that in mammals and has been verified to be the target of diamide insecticides . The anthranilic diamides represented by chlorantraniliprole (CHL) are the most significant class of insecticides to reduce losses caused by Lepidoptera and Coleoptera agricultural pests. , Since the diamide insecticides were commercialized, a huge market success (annual sales > USD 2.3 billion) has been witnessed, and the research on diamide insecticides continues to attract companies and research institutions. − Insecticides acting on this target do not have cross-resistance with other commonly used insecticides . However, due to its excellent control efficacy, the widespread and frequent use of diamide insecticide around the world has led to the emergence of resistance in some districts. − …”

“…The anthranilic diamides are characterized by the structures of anthranilic moiety and pyridine-pyrazole carboxylic moiety, and these two moieties exist in currently six commercial anthranilic diamide insecticides . Therefore, most of the resistant lepidopteran populations showed cross-resistance among these anthranilic diamides insecticides. , Point mutations in the amino acid sequence of RyR are the main cause of diamide resistance.…”