Biological activity of 2-methylbenzimidazole derivatives with heterocyclic rings on development of Bombyx mori

Derivatives of 1-heterocyclic 2-methylbenzimidazoles (HMBIs), prepared from previously reported 1-benzyl-2-methylbenzimidazoles, were synthesized to assess their larvicidal activity against the silkworm, Bombyx mori. Among the series, 2-methyl-1-(thiophen-2-yl)-methylbenzimidazole (SGH2) produces a distinctive biological phenotype characterized by growth retardation arising from epidermal abnormalities, together with defects in molting and pupation. To explore the basis of these effects, we examined the potential disruption of endocrine signaling as a causal mechanism. Specifically, we evaluated the binding of SGH2 to lepidopteran hemolymph juvenile hormone (JH)-binding protein (JHBP), an important modulator of insect hormone function, using a fluorescence-based ligand-sensor system that couples JHBP to two reporter fluorophores. SGH2 exhibited binding to JHBP with an EC50 of 2.13±0.34 µM, a potency comparable to that of JH. These findings indicate that HMBI derivatives, such as SGH2, can interfere with JH-mediated developmental processes in Lepidoptera and identify a promising scaffold for the design of novel insect growth regulators aimed at controlling lepidopteran pests.