| Title : Structure-activity relationship, in vitro and in vivo evaluation of novel dienyl sulphonyl fluorides as selective BuChE inhibitors for the treatment of Alzheimer's disease - Wu_2021_J.Enzyme.Inhib.Med.Chem_36_1860 |
| Author(s) : Wu C , Zhang G , Zhang ZW , Jiang X , Zhang Z , Li H , Qin HL , Tang W |
| Ref : J Enzyme Inhib Med Chem , 36 :1860 , 2021 |
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Abstract :
To discover novel scaffolds as leads against dementia, a series of delta-aryl-1,3-dienesulfonyl fluorides with alpha-halo, alpha-aryl and alpha-alkynyl were assayed for ChE inhibitory activity, in which compound A10 was identified as a selective BuChE inhibitor (IC(50) = 0.021 microM for eqBChE, 3.62 microM for hBuChE). SAR of BuChE inhibition showed: (i) o- > m- > p-; -OCH(3) > -CH(3) > -Cl (-Br) for delta-aryl; (ii) alpha-Br > alpha-Cl, alpha-I. Compound A10 exhibited neuroprotective, BBB penetration, mixed competitive inhibitory effect on BuChE (K(i) = 29 nM), and benign neural and hepatic safety. Treatment with A10 could almost entirely recover the Abeta(1-42)-induced cognitive dysfunction to the normal level, and the assessment of total amount of Abeta(1-42) confirmed its anti-amyloidogenic profile. Therefore, the potential BuChE inhibitor A10 is a promising effective lead for the treatment of AD. |
| PubMedSearch : Wu_2021_J.Enzyme.Inhib.Med.Chem_36_1860 |
| PubMedID: 34425715 |
Wu C, Zhang G, Zhang ZW, Jiang X, Zhang Z, Li H, Qin HL, Tang W (2021)
Structure-activity relationship, in vitro and in vivo evaluation of novel dienyl sulphonyl fluorides as selective BuChE inhibitors for the treatment of Alzheimer's disease
J Enzyme Inhib Med Chem
36 :1860
Wu C, Zhang G, Zhang ZW, Jiang X, Zhang Z, Li H, Qin HL, Tang W (2021)
J Enzyme Inhib Med Chem
36 :1860