| Title : Design, synthesis and evaluation of novel tacrine-multialkoxybenzene hybrids as dual inhibitors for cholinesterases and amyloid beta aggregation - Luo_2011_Bioorg.Med.Chem_19_763 |
| Author(s) : Luo W , Li YP , He Y , Huang SL , Tan JH , Ou TM , Li D , Gu LQ , Huang ZS |
| Ref : Bioorganic & Medicinal Chemistry , 19 :763 , 2011 |
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Abstract :
A new series of tacrine-multialkoxybenzene hybrids (9a-9n) were designed, synthesized and evaluated as dual inhibitors of cholinesterases (ChEs) and self-induced beta-amyloid (Abeta) aggregation. All the synthesized compounds had high acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity with IC(5)(0) values at the nanomolar range, which were much better than tacrine alone. A Lineweaver-Burk plot and molecular modeling study showed that these hybrids targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, compounds 9a-9f with methylenedioxybenzene moiety showed higher self-induced Abeta aggregation inhibitory activity than a reference compound, curcumin. These compounds could be selected as multi-potent agents for further investigation to treat AD. |
| PubMedSearch : Luo_2011_Bioorg.Med.Chem_19_763 |
| PubMedID: 21211982 |
Luo W, Li YP, He Y, Huang SL, Tan JH, Ou TM, Li D, Gu LQ, Huang ZS (2011)
Design, synthesis and evaluation of novel tacrine-multialkoxybenzene hybrids as dual inhibitors for cholinesterases and amyloid beta aggregation
Bioorganic & Medicinal Chemistry
19 :763
Luo W, Li YP, He Y, Huang SL, Tan JH, Ou TM, Li D, Gu LQ, Huang ZS (2011)
Bioorganic & Medicinal Chemistry
19 :763