Alzheimer’s disease (AD) is the most common form of dementia. The cholinesterase enzymes (ChEs), i.e., AChE and butyrylcholine esterase (BChE) inhibitors, are the most promising therapeutic strategy. Firstly, it can halt proteolytic degradation of the ACh into choline and acetic acid. Secondly, it increases ACh levels in the synaptic cleft to regulate cholinergic neurotransmission. In addition, AChE and BChE were also observed to promote Aβ-aggregation and the formation of neocortical Aβ-plaques and neurofibrillary tangles.

SD-6 is an orally active hAChE/hBChE inhibitor and can be used for research on Alzheimer’s disease.

SD-6 is an orally active inhibitor of hAChE and hBChE with IC₅₀ values of 0.907 µM and 1.579 µM, respectively. At first, it has an excellent blood-brain barrier (BBB) permeability and no neurotoxicity. In addition, SD-6 (5-80 µM; 24 h) has neuroprotective effects in SH-SY5Y cells. In vivo, First, SD-6 (100, 300, and 500 mg/kg; p.o.; single dose) has no toxic effect on nonpregnant female Wistar rats. Second, SD-6 (2.5, 5 and 10 mg/kg; p.o.; 3 times a day for 7 days) improves cognitive and memory deficits induced by Scopolamine in male Wistar rats. Third, SD-6 (2.5, 5, and 10 mg/kg; p.o.; single dose) significantly improves the abnormalities induced by Scopolamine in rats and promotes the normalization of biochemical indicators.

In short, SD-6 is an orally active inhibitor of hAChE/hBChE and can be used for the research of Alzheimer’s disease.

Reference：

[1] Waiker DK, et al. ACS Omega. 2023;8(10):9394-9414.