%0 Journal Article
%T Thio-汕-D-glucosides: Synthesis and Evaluation as Glycosidase Inhibitors and Activators
%A Andrey V. Samoshin
%A Irina A. Dotsenko
%A Nataliya M. Samoshina
%A Andreas H. Franz
%A Vyacheslav V. Samoshin
%J International Journal of Carbohydrate Chemistry
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/941059
%X Structurally simple 1-thio-汕-D-glucopyranosides were synthesized and tested as potential inhibitors toward several fungal glycosidases from Aspergillus oryzae and Penicillium canescens. Significant selective inhibition was observed for 汐- and 汕-glucosidases, while a weak to moderate activation for 汐- and 汕-galactosidases. 1. Introduction Thioglycosides are the hydrolysis- and metabolism-resistant synthetic S-analogs of natural O-glycosides. They attracted recently a rapidly increasing attention as competitive inhibitors of glycosidases and other enzymes involved in a variety of biochemical processes [1, 2] related in particular to metabolic disorders and diseases, such as diabetes [1, 3], to inflammations [2, 4] and viral or bacterial infections [5每17], including tuberculosis [9, 10], and to cancer [2, 18每20]. However, surprisingly little is known about the inhibition of glucosidases by 1-thio-汕-D-glucosides so far [21每24] (see the discussion). In a search for simple, readily accessible, and efficient glycosidase inhibitors [25每27], we designed, prepared, and assayed a series of structurally simple 1-thio-汕-D-glucosides. 2. Results and Discussion 2.1. Synthesis of 1-Thio-汕-D-glucopyranosides A series of aryl and alkyl 1-thio-汕-D-glucopyranosides 2a每2i was synthesized according to Scheme 1. In addition to the model compounds 2a每2f with simple aryl and alkyl aglycones, we included the phenanthroline derivative 2g, which was found to possess activity towards some glycosidases [27]. Compounds 2h每2iˋˋwere designed as disaccharide analogues in view of the significant inhibitory activity of the 1,2-cyclohexanedicarboxylic acid derivatives towards fungal glycosidases [25, 26]. Scheme 1: Preparation of 1-thio- 汕-D-glucopyranosides 2a每2i. The structures of all products and intermediates were determined from the data of 1H NMR and 13C NMR, including COSY and HMQC techniques. Thanks to a bias of the conformational equilibria towards the all-equatorial form of the pyranose ring, the configurational assignment was rather straightforward: large spin-spin coupling constants (9每11ˋHz) indicated a trans-diaxial orientation of the corresponding vicinal protons, while all other relative positions (axial-equatorial and equatorial-equatorial) resulted in small couplings between them (2每4ˋHz). 2.2. Glycosidase Inhibitory Activity The synthesized compounds have been assayed for enzyme inhibitory activity against several glycosidases in multienzyme complexes isolated from fungi Penicillium canescens and Aspergillus oryzae [28每32]. The multienzyme complex from P. canescens
%U http://www.hindawi.com/journals/ijcc/2014/941059/