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.
ABSTRACT
Bacteria resistance to antibacterial antibiotics is made possible by theproduction of beta-lactamase. Beta-lactamase enzyme confers resistance by breakingopen the Beta-lactam structure of antibiotics, thereby deactivating their antibacterialproperties. As a result of this, attention shifted into identifying potential lead inhibitorof beta-lactamase, with ability to reduce resistance encountered in bacteria antibiotics.The computational approach was employed in the generation of QSAR model usingAutomated QSAR, and in the docking of ligands from Chromolaena odorata with Betalactamase. The best model obtained was KPLS_Dendritic_43 (R2 = 0.8564 andQ2=0.7819), and was used in predicting the bioactivity of the lead compounds. Dockingstudy revealed that the ligands bind with a higher binding score than co-crystallizedligand and other standard drug employed in this study. Tianshic acid and chromomoraterecorded binding energy of -9.305 and -7.989 respectively. The drug-like properties ofthe ligands were evaluated using the Lipinski rule of Five, which revealed that C. odorataligands do not only inhibit the activity of beta-lactamase, but the ligands are also druglike. Therefore, further studies are needed to adequately justify the mechanism of actionof these ligands as a beta-lactamase inhibitor.