<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="6.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Brás, Natércia F.</style></author><author><style face="normal" font="default" size="100%">Neves, Rui P.P.</style></author><author><style face="normal" font="default" size="100%">Lopes, Filipa A.A.</style></author><author><style face="normal" font="default" size="100%">Correia, Márcia A. S.</style></author><author><style face="normal" font="default" size="100%">Palma, Angelina S.</style></author><author><style face="normal" font="default" size="100%">Sousa, Sérgio F.</style></author><author><style face="normal" font="default" size="100%">Ramos, Maria J.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Combined in silico and in vitro studies to identify novel antidiabetic flavonoids targeting glycogen phosphorylase</style></title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Biophysical chemistry</style></keyword><keyword><style  face="normal" font="default" size="100%">Enzyme inhibition</style></keyword><keyword><style  face="normal" font="default" size="100%">Free-energy calculations</style></keyword><keyword><style  face="normal" font="default" size="100%">Microscale thermophoresis</style></keyword><keyword><style  face="normal" font="default" size="100%">Prenylflavonoids</style></keyword><keyword><style  face="normal" font="default" size="100%">Type 2 diabetes</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2021</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2021</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">https://www.sciencedirect.com/science/article/pii/S0045206820318502</style></url></web-urls></urls><volume><style face="normal" font="default" size="100%">108</style></volume><pages><style face="normal" font="default" size="100%">104552</style></pages><isbn><style face="normal" font="default" size="100%">0045-2068</style></isbn><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">&lt;p&gt;Novel pharmacological strategies for the treatment of diabetic patients are now focusing on inhibiting glycogenolysis steps. In this regard, glycogen phosphorylase (GP) is a validated target for the discovery of innovative antihyperglycemic molecules. Natural products, and in particular flavonoids, have been reported as potent inhibitors of GP at the cellular level. Herein, free-energy calculations and microscale thermophoresis approaches were performed to get an in-depth assessment of the binding affinities and elucidate intermolecular interactions of several flavonoids at the inhibitor site of GP. To our knowledge, this is the first study indicating genistein, 8-prenylgenistein, apigenin, 8-prenylapigenin, 8-prenylnaringenin, galangin and valoneic acid dilactone as natural molecules with high inhibitory potency toward GP. We identified: i) the residues Phe285, Tyr613, Glu382 and/or Arg770 as the most relevant for the binding of the best flavonoids to the inhibitor site of GP, and ii) the 5-OH, 7-OH, 8-prenyl substitutions in ring A and the 4′-OH insertion in ring B to favor flavonoid binding at this site. Our results are invaluable to plan further structural modifications through organic synthesis approaches and develop more effective pharmaceuticals for Type 2 Diabetes treatment, and serve as the starting point for the exploration of food products for therapeutic usage, as well as for the development of novel bio-functional food and dietary supplements/herbal medicines.&lt;/p&gt;
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