Pharmacophore study, molecular docking and molecular dynamic simulation of virgin coconut oil derivatives as anti-inflammatory agent against COX-2

Abstract

Background Virgin coconut oil is mostly made up of saturated fatty acids in which approximately 72% are medium chain triglycerides. Medium chain triglycerides can be digested into medium chain fatty acids and medium chain monoglycerides which are bioactive components. Therefore, it is very important to study the in-silico ability of some Virgin coconut oil derivatives, namely, medium chain fatty acids and medium chain monoglycerides to inhibit Cyclooxygenase 2 (COX-2) protein for prevention of excessive inflammatory response. Results Pharmacophore study displayed monolaurin with two hydrogen bond donor, three hydrogen bond acceptor and five hydrophobic interactions, while lauric acid presented two hydrogen bond acceptor, five hydrophobic interactions and a negative ion interaction. Molecular docking underlined the ability of monolaurin in the inhibition of COX-2 protein which causes inflammatory action with a decent result of energy binding affinity of − 7.58 kcal/mol and 15 interactions out of which 3 are strong hydrogen bond with TYR385 (3.00 Å), PHE529 (2.77 Å), and GLY533 (3.10 Å) residues of the protein. Monolaurin was employed as hydrogen bond acceptor to the side of residue TYR385 of COX-2 protein with an occupancy of 67.03% and was observed to be long-living during the entire 1000 frames of the molecular dynamic simulation. The analysis of RMSD score of the Monolaurin–COX-2 complex backbone was calculated to be low (1.137 $$\pm$$ ± 0.153 Å) and was in a stable range of 0.480 to 1.520 Å. Redocking of this complex still maintained a strong hydrogen bond (2.87 Å) with the main residue TYR385. AMDET results where promising for medium chain fatty acids and medium chain monoglycerides with good physicochemical drug scores. Conclusions This can be concluded from the results obtained that the monolaurin has strong interactions with COX-2 protein to disrupt its function due to significant hydrogen bonds and hydrophobic interactions with amino acid residues present in the target protein’s active site. These results displayed a very significant anti-inflammatory potential of monolaurin and a new promising drug candidates as anti-inflammatory agent. Graphical Abstract

Discovery of andrographolide hit analog as a potent cyclooxygenase-2 inhibitor through consensus MD-simulation, electrostatic potential energy simulation and ligand efficiency metrics

“…The efficacy of this analog was compared with other natural compounds as well as synthetic compounds for COX-2 inhibition. The binding energy for A3 from docking analysis was found to be − 8.56 kcal/mol which is better than virgin coconut oil derivatives (BE range for the derivatives: − 5.65 kcal/mol to − 7.58 kcal/mol), alliin (− 4.90 kcal/mol), pinoresinolm (− 8.38 kcal/mol), and syringaresinol (− 8.23 kcal/mol) [90][91][92][93] . Further, MD simulation as well as EPE docking simulation analysis were carried for the complex stability for A3.…”

3D‐QSAR pharmacophore modeling, virtual screening, molecular docking, MD simulations, in vitro and in vivo studies to identify potential anti‐hyperplasia drugs

“…It also influences the selectivity, affinity for binding, and stabilizing effect of the small molecules with the receptor. [71,72] MD simulation was run for the top five hits using the Schrodinger software for 100 ns. Two molecules, that is, Ebs and Mbv showed the The Root Mean Square Fluctuation (RMSF) informs us about the fluctuations that are indicated in the protein chain.…”

“…Similarly From reported studies, the therapeutic index suggests that Ebs has a broad therapeutic range. [71]…”