Identification of Gly/NMDA receptor Antagonist from Chromolaena odorata’s Derived compounds using Induced Fit Docking and ADME study

The ionotropic activation of N-methyl-D-aspartic acid (NMDA) plays asignificant role in different type of neurodegenerative disease, as it is a tetramer withtwo Glycine binding subunit and two glutamate subunits. NMDA receptor can beinhibited by either blocking of the glycine site or glutamate site. Previously reportedinhibitors of NMDA receptor focus on the inhibition of the glutamate subunit, which wasreported to be associated with side effects such as ataxia, memory deficits, andneurotoxicity. Therefore, different compounds with antagonistic effect are beenexplored on Gly/NMDA site. Glide XP docking was employed in screening phytoconstituent of Chromolaena odorata against Gly/NMDA receptor for hit compounds withantagonistic properties. The hit compounds were further subjected to Induced fitdocking (IFD) and Lipinski rule of five. The final selection was based on Rigid XP dockingscore using co-crystallized ligand as threshold docking score, interaction with receptorsite residues, and IFD score. Ferulic acid, caffeic acid and scutellarein recorded bindingaffinity of -8.752Kcal/mol, 10.004 Kcal/mol and -9.096 Kcal/mol respectively, which ishigher than the binding affinity of co-crystallized ligand. Induced fit score obtained were-614.38, -614.03 and -616.31 for ferulic acid, caffeic acid and scutellarein respectively.The result obtained in this study shows the potency of phytochemical from C. odorata toinhibit NMDA receptor. ADME study showed that the drug-like nature of thesecompounds.

Lead finding from whole plant of Marrubium vulgare L. with Hepatoprotective Potentials through in silico methods

Objective: In the present study an attempt has been made to study the antihepatotoxic activity of active compounds in this plant through in silico methods. Methods: We have taken 12 compounds form this plant. All the compounds were further subjected to molecular propertied prediction and drug likeness by Molinspiration and found in compliance with Lipinski’s rule of five. Biochemical parameters like SGOT and SGPT were determined by Reitman and Frankel, ALP by Kind and King, TP by reported methods of Wooton. Results: All the compounds were showed expected similar bioactivity especially in case of enzyme inhibition. Compound Vulgarin showed no violation with good drug likeness score and biological activity as compare to standard drug Silibinin. Vulgarin exhibited a significant antihepatotoxic activity by reducing the elevated levels of serum enzymes such as serum glutamate oxaloacetate transaminase (SGOT) serum glutamate pyruvate oxaloacetate transaminase (SGPT) and alkaline phosphatase (ALP) while the total protein (TP) levels were increased when compared with standard drug silymarin against CCl4-induced toxicity in Wistar rats. These biochemical observations were also supplemented by histopathological examinations of the liver sections. Conclusions: We found that Vulgarin one of the twelve compounds is showed better drug likeness and biological activity against Silibinin. So this particular compound can be taken as lead compound for further drug discovery for hepatotoxic activity.