The binding of C5-alkynyl and alkylfurano[2,3-d]pyrimidine glucopyranonucleosides to glycogen phosphorylase b: Synthesis, biochemical and biological assessment

Synthesis of Novel Thiopurine Pyranonucleosides: Evaluation of Their Bioactivity

“…[12,13] In recent years, pyranosyl nucleosides are viewed as important modifications of natural nucleosides, offering promising avenues in the development of novel bioactive agents with promising therapeutic potential. [14][15][16][17][18][19][20][21][22][23][24] In our previous investigations, we demonstrated that base-modified pyranonucleosides rank among the most potent glycogen phosphorylase (GP) [25,26] and thymidylate synthase (TS) [27] inhibitors, and were endowed with a pronounced cytostatic and antiviral action. [28] As a continuation of this research and based on the pharmacological properties of thiopurine analogues, we now report the synthesis and biology of new thiopurine pyranonucleosides via glycosylation of mercaptopurine and thioguanine pyranonucleosides bearing D-glucose, D-galactose, D-xylose, D-mannose, and D-lyxose as sugar moiety.…”

Structure based inhibitor design targeting glycogen phosphorylase b. Virtual screening, synthesis, biochemical and biological assessment of novel N-acyl-β-d-glucopyranosylamines

“…Thus, it seems that the presence of the R group of the two inhibitors induces the between the phenyl rings of Phe285 and Tyr613, two residues that constitute the inhibitor site at the entrance of the catalytic site in GPb, resulting in its disruption. This rearrangement of the 280s loop is in the direction of the R to T allosteric conversion and has been also observed in other GPb ligand complexes with bulky benzoyl moieties [48][49][50] .…”

Synthesis of novel N-acyl-β-d-glucopyranosylamines and ureas as potential lead cytostatic agents

“…In view of the above observations and as a continuation of our long-term interest in glucopyranosyl analogues as antitumor/antiviral agents and potent enzyme inhibitors (Parmenopoulou et al, 2014;Dimopoulou et al, 2013;Manta et al, 2012;Kantsadi et al, 2012), it was envisaged that compounds bearing a glucopyranosyl moiety linked with various aralkyl and aralkenyl groups (Somsák et al, 2008a, b) via the pharmacophore linkers NHCO and NHCONHCO would be endowed with pronounced antitumor activity. We hereby report the facile synthesis and biological properties of novel acetylated as well as fully deprotected N-acyl-b-D-glucopyranosylamines (3a-f, 4af) and ureas (6a-f, 7a-f), respectively.…”