Virtual Screening and Pharmacokinetic Studies of Potential MAO-B Inhibitors from Traditional Chinese Medicine

ABSTRACT

Parkinson’s disease (PD) is a chronic neurological disorder of the nervoussystem, initiated by lessened production of dopamine (DA) in the substantia nigra, itaffects circa 50 percent more men than women. Theories reveal that age, genetic andenvironmental factors are involved in PD etiology but age seems to be the mostprominent risk factor. Monoamine oxidase B (MAO-B) play prominent role in theoxidative deamination of DA in the striatum. Inhibition of MAO-B in the brain maydecrease the exhaustion of DA stores and increase endogenous DA level. Glide-XPdocking, Quantum-mechanics Polarized Ligand Docking (QPLD), pharmacokineticstudies and biological activity prediction studies were utilized to explain the bindingmode, molecular interaction, inhibitory potential and pharmacokinetic properties ofTraditional Chinese Medicine (TCM) compounds on MAO-B and compared to standarddrugs used for treatment of PD, selegiline and rasagiline. Molecular docking resultsshowed Rutaecarpine and Chrysophanol to have relatively better inhibitory activitiesthan selegiline and rasagiline. Pharmacokinetic studies revealed that Rutaecarpine andChrysophanol show comparative result with selegiline and rasagiline. Also,Rutaecarpine and Chrysophanol PASS prediction for their monoamine inhibitoryactivity showed greater Pa than Pi value. Our results have shown that Rutaecarpine andChrysophanol can be a better therapeutic candidate in the treatment of PD.