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Amplification of the Inhibitory Activity and Reversal of the Selectivity of Miglitol by C(2′)‐Monofluorination
Author(s) -
Prell Erik,
Korb Claudia,
Kluge Ralph,
Ströhl Dieter,
Csuk René
Publication year - 2010
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200900256
Subject(s) - chemistry , substituent , cytotoxicity , selectivity , stereochemistry , glycoside hydrolase , enzyme , inhibitory postsynaptic potential , lead compound , enzyme inhibitor , cell culture , biochemistry , in vitro , biology , catalysis , neuroscience , genetics
Selective monofluorination of the α‐glycosidase inhibitor and antidiabetic agent miglitol at positions C(2′) or C(6) creates competitive inhibitors of glycosidases. Introducing a fluorine substituent at position C(6) results in a reduced binding to the enzyme whereas fluorination at C(2′) produces an inhibitor with an activity four times higher than the parent compound. This compound is selective for the α‐galactosidase from green coffee beans. Its screening against a panel of human cell lines showed a low cytotoxicity, therefore, making this compound an interesting candidate for further clinical investigations.