High expression of glutaminyl cyclase (QC) contributes to the initiation of Alzheimer’s disease (AD) by catalyzing the generation of neurotoxic pyroglutamate (pE)-modified β-amyloid (Aβ) peptides. Preventing the generation of pE-Aβs by QC inhibition has been suggested as a novel approach to a disease-modifying therapy for AD. In this work, a series of diphenyl conjugated imidazole derivatives (DPCIs) was rationally designed and synthesized. Analogues with this scaffold exhibited potent inhibitory activity against human QC (hQC) and good in vitro blood–brain barrier (BBB) permeability. Further assessments corroborated that the selected hQC inhibitor 28 inhibits the activity of hQC, dramatically reduces the generation of pE-Aβs in cultured cells and in vivo, and improves the behavior of AD mice.

Glutaminyl cyclase (QC) plays an important role in the pathogenesis of Alzheimer’s disease (AD) and can be a potential target for the development of novel anti-AD agents. However, the study of QC inhibitors are still less. Here, phenol-4′ (R1-), C5-OH (R2-) and C7-OH (R3-) modified apigenin derivatives were synthesized as a new class of human QC (hQC) inhibitors. The efficacy investigation of these compounds was performed by spectrophotometric assessment and the structure–activity relationship (SAR) was evaluated. Molecular docking was also carried out to analyze the binding mode of the synthesized flavonoid to the active site of hQC.

In our effort to develop novel plant-derived acaricides, we examined the contact and fumigant toxicity of Asarum heterotropoides (Asarum sieboldii Miquel) essential oil constituents to the house dust mite Dermatophagoides farinae (Acari: Pyroglyphidae). Ten constituents, including methyl eugenol (relative amount 42.18 %), were identified by gas chromatography-mass spectroscopy (GC-MS) in the A. sieboldii Miq. essential oil. In contact toxicity tests, methyl eugenol (4.2 μg/cm2, 24 h LD50) was most toxic to D. farinae, followed by benzyl benzoate (9.1 μg/cm2), A. sieboldii Miq. essential oil (37.7 μg/cm2), and dibutyl phthalate (DBP 57.9 μg/cm2). The potency of methyl eugenol and A. sieboldii Miq. essential oil was higher than benzyl benzoate and DBP, with mortalities of 100, 100, 94.6, and 13.2 %, respectively, after 2.5 h of exposure. In the vapor phase mortality bioassay, methyl eugenol and A. sieboldii Miq. essential oil resulted in 100 % mortality in closed containers after 24-h exposure, but only 4.7 and 7.9 %, respectively, in open containers, indicating that the toxicity in these tests was largely due to the vapor phase. Methyl eugenol and A. sieboldii Miq. essential oil merit further study as potential D. farinae control compounds.