Paper Report for: Wang_2012_Bioorg.Med.Chem_20_6513
Reference
Title: Novel multipotent phenylthiazole-tacrine hybrids for the inhibition of cholinesterase activity, beta-amyloid aggregation and Ca(2+) overload 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 : PubMed
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.
        
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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 Chemistry20: 6513-22
Wang Y, Wang F, Yu JP, Jiang FC, Guan XL, Wang CM, Li L, Cao H, Li MX, Chen JG (2012) Bioorganic & Medicinal Chemistry20: 6513-22