New N-(phenoxydecyl)phthalimide derivatives displaying potent inhibition activity towards alpha-glucosidase.
Several members of a new family of non-sugar-type alpha-glucosidase inhibitors, bearing a phthalimide moiety connected to a variously substituted phenoxy ring by an alkyl chain, were synthesized and their activities were investigated. The efficacy of the inhibition activity appeared to be governed by the chain length of the substrate. Substrates possessing 10 carbons afforded the highest levels of activity, which were one to two orders of magnitude more potent than the known inhibitor 1-deoxynojirimycin (dNM). Furthermore, structure-activity relationship studies indicated a critical role of electron-withdrawing substituents at the phenoxy group for the activity. Derivatives bearing a chlorine atom along with a strong electron-withdrawing group, such as a nitro group, were the most potent of the series.
Pascale
Rossana
R
Dipartimento Farmaco-Chimico, Università degli Studi di Bari, 70126 Bari, Italy.
Carocci
Alessia
A
Catalano
Alessia
A
Lentini
Giovanni
G
Spagnoletta
Anna
A
Cavalluzzi
Maria Maddalena
MM
De Santis
Francesco
F
De Palma
Annalisa
A
Scalera
Vito
V
Franchini
Carlo
C
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D010797:Phthalimides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism
D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D010797:Phthalimides; D000520:alpha-Glucosidases