Anti‐Epileptic Drug‐Lipid Conjugates for Delivery to the Brain: In Silico ADMET Prediction, Molecular Docking and Molecular Dynamics Simulations

Abstract

AbstractNeurological disease epilepsy has unfortunately become widespread, affecting around 50 million individuals worldwide. Levetiracetam (LVM) is a newer‐generation drug but its hydrophilic nature restricts its BBB (blood‐brain barrier) permeability. This results in increased dose, dosing frequency, and side effects. Therefore, different lipid‐drug conjugates (LDCs) were studied to identify the compound capable of BBB permeation. The binding potential of LDCs with human brain fatty‐acid binding protein (HBFABP) (PDB id: 1FDQ) was determined by molecular docking through extra‐precision (XP) algorithm of Maestro. In simulations, OPLS3e force field was applied. The ADMET prediction was performed by QikProp and pkCSM web tool. The selected compounds were investigated for LDC‐BFABP complex stability through molecular dynamics (MD) study. All compounds indicated good pharmacokinetic profiles. The LVM‐palmitic acid and LVM‐stearic acid conjugates indicated higher docking scores and greater stability than LVM alone. Thus, they can be selected as potential molecules for further drug development to obtain clinically useful LDC for treatment of CNS disorder.