| Title : Novel multipotent phenylthiazole-tacrine hybrids for the inhibition of cholinesterase activity, beta-amyloid aggregation and Ca(2+) overload - Wang_2012_Bioorg.Med.Chem_20_6513 |
| Author(s) : Wang Y , Wang F , Yu JP , Jiang FC , Guan XL , Wang CM , Li L , Cao H , Li MX , Chen JG |
| Ref : Bioorganic & Medicinal Chemistry , 20 :6513 , 2012 |
| Abstract : In this study, a series of multipotent phenylthiazole-tacrine hybrids (7a-7e, 8, and 9a-9m) were synthesized and biologically evaluated. Screening results showed that phenylthiazole-tacrine hybrids were potent cholinesterase inhibitors with pIC(50) (-logIC(50)) value ranging from 5.78+/-0.05 to 7.14+/-0.01 for acetylcholinesterase (AChE), and from 5.75+/-0.03 to 10.35+/-0.15 for butyrylcholinesterase (BCHE). The second series of phenylthiazole-tacrine hybrids (9a-9m) could efficiently prevent Abeta(1-42) self-aggregation. The structure-activity relationship revealed that their inhibitory potency relied on the type of middle linker and substitutions at 4'-position of 4-phenyl-2-aminothiazole. In addition, 7a and 7c also displayed the Ca(2+) overload blockade effect in the primary cultured cortical neurons. Consequently, these compounds emerged as promising molecules for the therapy of Alzheimer's disease. |
| ESTHER : Wang_2012_Bioorg.Med.Chem_20_6513 |
| PubMedSearch : Wang_2012_Bioorg.Med.Chem_20_6513 |
| PubMedID: 23000296 |
Wang Y, Wang F, Yu JP, Jiang FC, Guan XL, Wang CM, Li L, Cao H, Li MX, Chen JG (2012)
Novel multipotent phenylthiazole-tacrine hybrids for the inhibition of cholinesterase activity, beta-amyloid aggregation and Ca(2+) overload
Bioorganic & Medicinal Chemistry
20 :6513
Wang Y, Wang F, Yu JP, Jiang FC, Guan XL, Wang CM, Li L, Cao H, Li MX, Chen JG (2012)
Bioorganic & Medicinal Chemistry
20 :6513