Discovery of 3-Formyl-N-(un)Substituted Benzylindole Pyrimidines as an Acaricidal Agent and Their Mechanism of Action

Abstract

To discover the pronounced acaricide candidate, herein, a series of 3-formyl-N-(un)­substituted benzylindole pyrimidines were prepared by structural modification of indoles at the N-1 and C-3 positions via the successive Vilsmeier–Haack–Arnold (VHA), aldol condensation, and cyclization reactions. The steric structures of nine compounds were undoubtedly confirmed by X-ray single-crystallography. Against Tetranychus cinnabarinus Boisduval, compounds V-15, V-31, V-34, V-42, V-44, and V-60 exhibited promising acaricidal activity with LC50 values of 0.299–0.481 mg/mL. In particular, compound V-34 displayed 4.2 times the acaricidal activity of its precursor 6-methylindole. Scanning electron microscopy (SEM) imaging revealed that the construction of the cuticle layer of V-34-treated T. cinnabarinus was seriously destroyed. Furthermore, RNA-Seq analysis indicated that compound V-34 could regulate the homeostasis metabolism of T. cinnabarinus through arachidonic acid and linoleic acid metabolism and lysosome pathways. These results suggested that compound V-34 can be further studied as a lead acaricidal agent.

Construction and Single-Crystal Structures of N-Isoxazolin-5-ylcarbonylindole Derivatives, and Their Pesticidal Activities and Toxicology Study

“…The acaricidal activity of compounds 1a – c , 2a – c , and 3a – x was evaluated against female adults of T. cinnabarinus …”

“…Control effects of compounds 1a , 1b , 3b , and 3l were tested against female adults of T. cinnabarinus in the glasshouse …”