PMID- 20865534
OWN - NLM
STAT- MEDLINE
DCOM- 20110203
LR  - 20181201
IS  - 0065-2598 (Print)
IS  - 0065-2598 (Linking)
VI  - 680
DP  - 2010
TI  - Modeling of ATP-sensitive inward rectifier potassium channel 11 and inhibition 
      mechanism of the natural ligand, ellagic acid, using molecular docking.
PG  - 489-95
LID - 10.1007/978-1-4419-5913-3_55 [doi]
AB  - 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.
FAU - Mathew, Alex J
AU  - Mathew AJ
AD  - Department of Bioinformatics, Sathyabama University, Chennai, 600119 Tamil Nadu, 
      India. mathponz@yahoo.co.in
FAU - Raj, Nixon N
AU  - Raj NN
FAU - Sugappriya, M
AU  - Sugappriya M
FAU - Priyadarshini, Sangeetha M
AU  - Priyadarshini SM
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Adv Exp Med Biol
JT  - Advances in experimental medicine and biology
JID - 0121103
RN  - 0 (Cyclohexanes)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (KATP Channels)
RN  - 0 (Ligands)
RN  - 0 (Sulfonylurea Compounds)
RN  - 19YRN3ZS9P (Ellagic Acid)
RN  - 41X3PWK4O2 (Nateglinide)
RN  - 47E5O17Y3R (Phenylalanine)
RN  - 6KY687524K (glimepiride)
SB  - IM
MH  - Binding Sites
MH  - Caco-2 Cells
MH  - Computational Biology
MH  - Computer-Aided Design
MH  - Cyclohexanes/pharmacology
MH  - Drug Design
MH  - Drug Discovery
MH  - Ellagic Acid/chemistry/pharmacokinetics/*pharmacology
MH  - Humans
MH  - Hypoglycemic Agents/chemistry/pharmacokinetics/pharmacology
MH  - In Vitro Techniques
MH  - KATP Channels/*antagonists & inhibitors/*chemistry
MH  - Ligands
MH  - Models, Molecular
MH  - Nateglinide
MH  - Phenylalanine/analogs & derivatives/pharmacology
MH  - Structural Homology, Protein
MH  - Sulfonylurea Compounds/pharmacology
EDAT- 2010/09/25 06:00
MHDA- 2011/02/04 06:00
CRDT- 2010/09/25 06:00
PHST- 2010/09/25 06:00 [entrez]
PHST- 2010/09/25 06:00 [pubmed]
PHST- 2011/02/04 06:00 [medline]
AID - 10.1007/978-1-4419-5913-3_55 [doi]
PST - ppublish
SO  - Adv Exp Med Biol. 2010;680:489-95. doi: 10.1007/978-1-4419-5913-3_55.