Novel multipotent phenylthiazole-tacrine hybrids for the inhibition of cholinesterase activity, ß-amyloid aggregation and Ca²âº overload.
Bioorg Med Chem
; 20(21): 6513-22, 2012 Nov 01.
Article
em En
| MEDLINE
| ID: mdl-23000296
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 (BuChE). The second series of phenylthiazole-tacrine hybrids (9a-9m) could efficiently prevent Aß(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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Tacrina
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Tiazóis
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Cálcio
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Inibidores da Colinesterase
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Colinesterases
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Peptídeos beta-Amiloides
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article