作者: Ben A. Chetter , Efthimios Kyriakis , Daniel Barr , Aikaterini G. Karra , Elisabeth Katsidou
DOI: 10.1016/J.BIOORG.2020.104003
关键词:
摘要: Abstract Glycogen phosphorylase (GP) is an important target for the development of new anti-hyperglycaemic agents. Flavonoids are novel inhibitors GP, but their mode action unspecific in terms GP binding sites involved. Towards design synthetic flavonoid analogues acting specifically at inhibitor site and to exploit site’s hydrophobic pocket, chrysin has been employed as a lead compound silico screening 1169 with different B ring substitutions. QM/MM-PBSA free energy calculations guided final selection eight compounds, subsequently synthesised using Baker-Venkataraman rearrangement-cyclisation approach. Kinetics experiments against rabbit muscle GPa GPb together human liver GPa, revealed three these compounds (11, 20 43) among most potent that bind (Ki s