ABSTRACT
The use of antidiabetic agents which control glycemic levels in the blood and simultaneously inhibit oxidative stress is an important strategy in the prevention of Diabetes Mellitus and its complications. In our previous study, malabaricone C (3) and its dimer, giganteone A (5) exhibited significant DPPH free radical scavenging activities which were lower than the activity of the positive control, ascorbic acid. These compounds were evaluated for their α-glucosidase inhibitory activities at different concentrations (0.02-2.5 mM) in the present study. Compounds 3 (IC50 59.61 µM) and 5 (IC50 39.52 µM) were identified as active alpha-glucosidase inhibitors, each respectively being 24 and 37 folds more potent than the standard inhibitor, acarbose. Based on the molecular docking studies, compounds 3 and 5 docked into the active site of the α-glucosidase enzyme, forming mainly hydrogen bonds in the active site.
Subject(s)
Diabetes Mellitus , Glycoside Hydrolase Inhibitors , Biphenyl Compounds , Diabetes Mellitus/drug therapy , Glycoside Hydrolase Inhibitors/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Molecular Docking Simulation , Resorcinols , Structure-Activity Relationship , alpha-Glucosidases/metabolismABSTRACT
The inhibition of carbohydrate-hydrolyzing enzymes in human digestive organs is crucial in controlling blood sugar levels, which is important in treating typeâ 2 diabetes. In the current study, pahangensin A (1), a bis-labdanic diterpene characterized previously in the rhizomes of Alpinia pahangensis Ridl., was identified as an active dual inhibitor for α-amylase (IC50 =114.80â µm) and α-glucosidase (IC50 =153.87â µm). This is the first report on the dual α-amylase and α-glucosidase inhibitory activities of a bis-labdanic diterpene. The Lineweaver-Burk plots of compound 1 indicate that it is a mixed-type inhibitor with regard to both enzymes. Based on molecular docking studies, compound 1 docked in a non-active site of both enzymes. The dual inhibitory activity of compound 1 makes it a suitable natural alternative in the treatment of typeâ 2 diabetes.
Subject(s)
Alpinia/chemistry , Diterpenes/chemistry , alpha-Amylases/metabolism , alpha-Glucosidases/metabolism , Alpinia/metabolism , Binding Sites , Catalytic Domain , Diterpenes/isolation & purification , Diterpenes/metabolism , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/metabolism , Kinetics , Molecular Docking Simulation , Plant Extracts/chemistry , alpha-Amylases/antagonists & inhibitors , alpha-Glucosidases/chemistryABSTRACT
A dimeric acylphenol and a potent α-glucosidase inhibitor, giganteone D (IC50 5.05µM), was isolated and characterized from the bark of Myristica cinnamomea King. The bark also yielded an acylphenol with an unprecedented skeleton for which the name cinnamomeone A (IC50 358.80µM) was proposed. Their structures were established by means of NMR and MS spectrometric analyses. The Lineweaver-Burk plot of giganteone D indicated that it was a mixed-type inhibitor. This is the first report on the α-glucosidase inhibiting potential of acylphenols.
