Pyrimidine-fused heterocycle derivatives as a novel class of inhibitors for α-glucosidase. (December 2013)

• Record Type: Journal Article
• Authors: Yousefi, Reza; Alavian-Mehr, Mohammad-Mehdi; Mokhtari, Fatemeh; Panahi, Farhad; Mehraban, Mohammad H.; Khalafi-Nezhad, Ali
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 28:Number 6(2013:Dec.)
• Page Start: 1228
• Page End: 1235
• Publication Date: 2013-12
• Subjects: Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2012.727812
• Languages: English
• ISSNs: 1475-6366

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>The needs for diverse inhibitors of α-glucosidase (α-Gls) encouraged us to synthesize five different poly-hydroxy functionalized pyrimidine-fused heterocyclic (PHPFH) molecules, having either aliphatic or aromatic side chains (<bold>C</bold><sub><bold>1</bold></sub><bold>–C</bold><sub><bold>5</bold></sub>) and their inhibitory activities were examined spectroscopically against yeast and mouse intestinal α-Gls. The results revealed that aromatic substitution of the synthetic compounds has significant impact on their inhibitory properties. Moreover <bold>C</bold><sub><bold>3</bold></sub> with the substituted moiety as 4-(4-aminophenylsulfonyl) phenyl (4-APSP) revealed strong inhibitory activity with non-competitive and competitive inhibition modes against yeast and mouse α-Gls, respectively. Furthermore, in the presence of increasing concentration of <bold>C</bold><sub><bold>3</bold></sub>, both Trp and 1-anilinonaphthalene-8-sulfonic acid (ANS) fluorescence intensities of yeast α-Gls were gradually decreased, suggesting that <bold>C</bold><sub><bold>3</bold></sub> binding induced significant structural alteration which was accompanied with the reduction of hydrophobic surfaces. Also, the interaction between yeast α-Gls and <bold>C</bold><sub><bold>3</bold></sub> was proved to be spontaneous and driven mainly by hydrophobic forces. Overall, this study suggests that aromatic substitution on pyrimidine-fused heterocyclic (PFH) scaffold may represent a novel class of promising inhibitors of α-Gls.</p> </abstract>