Open AccessST 09, a Novel Thioester Derivative of Tacrine, Alleviates Cognitive Deficits and Enhances Glucose Metabolism in Vascular Dementia Rats
Author(s) -
Liu JianMin,
Wu PengFei,
Rao Jing,
Zhou Jun,
Shen ZuCheng,
Luo Han,
Huang JianGeng,
Liang Xiao,
Long LiHong,
Xie QingGuo,
Jiang FengChao,
Wang Fang,
Chen JianGuo
Publication year - 2016
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12495
Subject(s) - tacrine , donepezil , acetylcholinesterase , vascular dementia , pharmacology , acetylcholinesterase inhibitor , chemistry , hippocampus , morris water navigation task , dementia , biochemistry , medicine , enzyme , disease
Summary Aims Chemical entities containing mercapto group have been increasingly attractive in the therapy of central nerve system ( CNS ) diseases. In the recent study, we screened a series of mercapto‐tacrine derivatives with synergistic neuropharmacological profiles in vitro . Methods We investigated the effect and mechanism of ST 09, a thioester derivative of tacrine containing a potential mercapto group, on the vascular dementia (VaD) model of rat induced by bilateral common carotid arteries occlusion (2‐ VO ). Results ST 09 and its active metabolite ST 10 retained excellent inhibition on acetylcholinesterase ( AC hE) activity. ST 09 significantly attenuated the 2‐ VO ‐induced impairment in spatial acquisition performance and inhibited the 2‐ VO ‐induced rise of AC hE activity. In the VaD model, ST 09 attenuated the oxidative stress and decreased the apoptosis in the cortex and hippocampus. Compared with donepezil, ST 09 exhibited a better effect on the regeneration of free thiols in 2‐ VO rats. Interestingly, ST 09, not donepezil, greatly improved glucose metabolism in various brain regions of 2‐ VO rats using functional imaging of 18 F‐labeled fluoro‐deoxyglucose ( FDG ) positron emission tomography ( PET ). Conclusions ST 09 may serve as a more promising agent for the therapy of VaD than tacrine owing to the introduction of a potential mercapto group into the parent skeleton.