Druggability and Binding Site Interaction Studies of Potential Metabolites Isolated from Marine Sponge Aurora globostellata against Human Epidermal Growth Factor Receptor-2.

To study the involvement of compounds stigmasterol and oleic acid isolated from marine sponge Aurora globostellata and docking against the Human Epidermal Growth Factor Receptor-2 in breast cancer. The comparative molecular docking was performed with the natural compounds from marine sponge and the synthetic drugs used in breast cancer treatment against the target HER2. The molecular docking analysis was done using GLIDE in Schrodinger software package. The ADME properties were calculated using the Qikprop. The observation of the common binding site for all the ligands confirms the binding pocket; where the isolated compound Stigmasterol agrees well with the binding residues and thus can be optimized further to arrive at a molecule that has a high binding affinity and low binding constant. The results of the docking studies carried out on HER2 provide an insight for the compound stigmasterol to have drug like properties than oleic acid. These results are supportive to confirm the marine sponges as a better lead for cancer therapeutics.

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.