Modeling of ATP-sensitive inward rectifier potassium channel 11 and inhibition mechanism of the natural ligand, ellagic acid, using molecular docking.
Diabetes mellitus is a disorder in which blood sugar (glucose) levels are abnormally high because the body does not produce enough insulin to meet its needs. Post-prandial hyperglycemia (PPHG) is an independent risk factor for the development of macro vascular complications. It is now recognized that normalizing post-prandial blood glucose is more difficult than normalizing fasting glucose. Potassium channels are the most widely distributed type of ion channel and are found in virtually all living organisms. The function of KATP channels is best understood in pancreatic beta cells, the membrane potential of which is responsive to external glucose concentration. Beta cells show a remarkably complex electrical bursting behavior in response to an increase in glucose level. Nateglinide and Glimepiride are a class of insulin secretagog agents that lowers blood glucose levels by stimulating insulin secretion from the pancreas. These compounds interact with the ATP-sensitive potassium (K+ATP) channel in pancreatic beta cells. However, the side effects of these drugs overpass their uses, and the need to identify compounds with less adverse effects is exigent. In our research study, we used the natural compound ellagic acid, which is an already proven anti-carcinogen, anti-mutagen, and anticancer initiator, for its anti-diabetic activity in comparison to the two commercial drugs (Nateglinide and Glimepiride). The drugs and the compounds were docked to the ATP-dependent potassium channel and their energy value showed that the compound had higher binding value than the commercial drugs. Then an ADME/Tox analysis for the compound was carried out which showed that ellagic can be a possible lead molecule.
Mathew
Alex J
AJ
Department of Bioinformatics, Sathyabama University, Chennai, 600119 Tamil Nadu, India. mathponz@yahoo.co.in
Raj
Nixon N
NN
Sugappriya
M
M
Priyadarshini
Sangeetha M
SM
D001665:Binding Sites; D018938:Caco-2 Cells; D019295:Computational Biology; D017076:Computer-Aided Design; D003510:Cyclohexanes / Q000494:pharmacology; D015195:Drug Design; D055808:Drug Discovery; D004610:Ellagic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D054086:KATP Channels / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D040681:Structural Homology, Protein; D013453:Sulfonylurea Compounds / Q000494:pharmacology
D003510:Cyclohexanes; D007004:Hypoglycemic Agents; D054086:KATP Channels; D008024:Ligands; D013453:Sulfonylurea Compounds; D004610:Ellagic Acid; D000077715:Nateglinide; D010649:Phenylalanine; C057619:glimepiride