scholarly journals Novel Liver-targeted conjugates of Glycogen Phosphorylase Inhibitor PSN-357 for the Treatment of Diabetes: Design, Synthesis, Pharmacokinetic and Pharmacological Evaluations

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Liying Zhang ◽  
Chengjun Song ◽  
Guangxin Miao ◽  
Lianzhi Zhao ◽  
Zhiwei Yan ◽  
...  
Keyword(s):  
Glycogen Phosphorylase ◽  
Design Synthesis ◽  
Treatment Of Diabetes ◽  
Glycogen Phosphorylase Inhibitor

scholarly journals Glycogen Phosphorylase-a is a Common Target for Anti-Diabetic Effect of Iridoid and Secoiridoid Glycosides

2013 ◽  
Vol 16 (4) ◽  
pp. 530 ◽  
Author(s):  
Hitesh B Vaidya ◽  
Abeer A Ahmed ◽  
Ramesh K Goyal ◽  
Sukhinder K Cheema
Keyword(s):  
Diabetes Mellitus ◽  
Medicinal Plants ◽  
Glycogen Phosphorylase ◽  
Docking Studies ◽  
Chemical Components ◽  
Active Components ◽  
Active Chemical ◽  
Treatment Of Diabetes ◽  
Secoiridoid Glycosides ◽  
Common Target

Purpose. Diabetes mellitus is characterized by hyperglycemia resulting from defects in insulin secretion, action or both. The use of medicinal plants for the treatment of diabetes mellitus dates back from the Ebers papyrus of about 1550 B.C. One of the major problems with herbal drugs is that the active ingredients are not well defined. It is important to know the active components and their molecular interactions which will help to analyze their therapeutic efficacy and also to standardize the product. There are a number of medicinal plants known for their anti-diabetic effect that possess similarities in their active chemical components, e.g. iridoid and secoiridoid glycosides. Methods. In this study, we have compared the structure of various iridoid and secoiridoid glycosides to design a novel pharmacophore. We further developed a structure-activity relationship for the inhibition of glycogen phosphorylase-a. Conclusion. By using docking studies, we are proposing, for the first time, that inhibition of glycogen phosphorylase-a activity is a common target for iridoids and secoiridoids to elicit anti-diabetic effects. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

ChemInform Abstract: Synthesis and Glycogen Phosphorylase Inhibitor Activity of Functionalized 1,4-Benzodioxanes.

ChemInform ◽  
2010 ◽  
Vol 41 (31) ◽  
pp. no-no
Author(s):  
Z. Czako ◽  
T. Docsa ◽  
P. Gergely ◽  
L. Luhasz ◽  
S. Antus
Keyword(s):  
Glycogen Phosphorylase ◽  
Inhibitor Activity ◽  
Glycogen Phosphorylase Inhibitor

Hepatic glycogen breakdown is implicated in the maintenance of plasma mannose concentration

2005 ◽  
Vol 288 (3) ◽  
pp. E534-E540 ◽  
Author(s):  
T. Taguchi ◽  
E. Yamashita ◽  
T. Mizutani ◽  
H. Nakajima ◽  
M. Yabuuchi ◽  
...  
Keyword(s):  
Glycogen Phosphorylase ◽  
Diabetic Rats ◽  
Hepatic Glycogen ◽  
Perfused Liver ◽  
Diabetes Model ◽  
Gluconeogenic Substrates ◽  
Glycogen Phosphorylase Inhibitor ◽  
Fasted Rats ◽  
Glycogen Breakdown

d-Mannose is an essential monosaccharide constituent of glycoproteins and glycolipids. However, it is unknown how plasma mannose is supplied. The aim of this study was to explore the source of plasma mannose. Oral administration of glucose resulted in a significant decrease of plasma mannose concentration after 20 min in fasted normal rats. However, in fasted type 2 diabetes model rats, plasma mannose concentrations that were higher compared with normal rats did not change after the administration of glucose. When insulin was administered intravenously to fed rats, it took longer for plasma mannose concentrations to decrease significantly in diabetic rats than in normal rats (20 and 5 min, respectively). Intravenous administration of epinephrine to fed normal rats increased the plasma mannose concentration, but this effect was negated by fasting or by administration of a glycogen phosphorylase inhibitor. Epinephrine increased mannose output from the perfused liver of fed rats, but this effect was negated in the presence of a glucose-6-phosphatase inhibitor. Epinephrine also increased the hepatic levels of hexose 6-phosphates, including mannose 6-phosphate. When either lactate alone or lactate plus alanine were administered as gluconeogenic substrates to fasted rats, the concentration of plasma mannose did not increase. When lactate was used to perfuse the liver of fasted rats, a decrease, rather than an increase, in mannose output was observed. These findings indicate that hepatic glycogen is a source of plasma mannose.

scholarly journals High Consistency of Structure-Based Design and X-Ray Crystallography: Design, Synthesis, Kinetic Evaluation and Crystallographic Binding Mode Determination of Biphenyl-N-acyl-β-d-Glucopyranosylamines as Glycogen Phosphorylase Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1322 ◽  
Author(s):  
Thomas Fischer ◽  
Symeon M. Koulas ◽  
Anastasia S. Tsagkarakou ◽  
Efthimios Kyriakis ◽  
George A. Stravodimos ◽  
...  
Keyword(s):  
Glycogen Phosphorylase ◽  
Catalytic Mechanism ◽  
Liver Glycogen ◽  
Binding Mode ◽  
Structural Water ◽  
Design Synthesis ◽  
Kinetic Evaluation ◽  
X Ray ◽  
X Ray Crystallography ◽  
Design And Synthesis

Structure-based design and synthesis of two biphenyl-N-acyl-β-d-glucopyranosylamine derivatives as well as their assessment as inhibitors of human liver glycogen phosphorylase (hlGPa, a pharmaceutical target for type 2 diabetes) is presented. X-ray crystallography revealed the importance of structural water molecules and that the inhibitory efficacy correlates with the degree of disturbance caused by the inhibitor binding to a loop crucial for the catalytic mechanism. The in silico-derived models of the binding mode generated during the design process corresponded very well with the crystallographic data.

Design, synthesis and SAR of novel sulfonylurea derivatives for the treatment of Diabetes mellitus in rats

2021 ◽  
Author(s):  
Farid M. Sroor ◽  
Wahid M. Basyouni ◽  
Hanan F. Aly ◽  
Sanaa A. Ali ◽  
Azza F. Arafa
Keyword(s):  
Diabetes Mellitus ◽  
Design Synthesis ◽  
Treatment Of Diabetes

Cardioprotective effect of the glycogen phosphorylase inhibitor CP-380867

2001 ◽  
Vol 33 (6) ◽  
pp. A178 ◽  
Author(s):  
J.L. Treadway ◽  
W.P. Magee ◽  
D.J. Hoover ◽  
R.K. McPherson ◽  
W.H. Martin ◽  
...  
Keyword(s):  
Glycogen Phosphorylase ◽  
Cardioprotective Effect ◽  
Glycogen Phosphorylase Inhibitor

scholarly journals Discovery of a human liver glycogen phosphorylase inhibitor that lowers blood glucose in vivo

1998 ◽  
Vol 95 (4) ◽  
pp. 1776-1781 ◽  
Author(s):  
W. H. Martin ◽  
D. J. Hoover ◽  
S. J. Armento ◽  
I. A. Stock ◽  
R. K. McPherson ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Human Liver ◽  
Glycogen Phosphorylase ◽  
Liver Glycogen ◽  
Glycogen Phosphorylase Inhibitor
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