Comparative Analysis of Potentiality of Esculin and Hinokitol (Β-Thujaplicin) as Anti-Parkinsonism Drugs: A Pilot in Silico Study

Abstract

<p><strong>Objective: </strong>Parkinson’s disease (PD) is a leading cause of mental disability and death worldwide. Even though there are many advances in drug development against PD, a potent low dosage drug with fewer side effects are still in its nursery. This is a pioneer <em>in silico</em> attempt to test the anti-PD actions of esculin and hinokitol to act novel drugs.</p><p><strong>Methods: </strong>In this study, using Auto dock tools 4.2, esculin and hinokitol (β-Thujaplicin) were predicted for its inhibitory actions with Alpha-Synuclein (AS) Apo site, Dopamine D3 Receptor (D3R), Glycogen Synthase Kinase-3 Beta (GSK3β), Mono Oxidase B (MAO-B), Parkin and Tyrosine 3-Hydroxylase (TH) with levodopa standard. The reliability of the 3D predicted model of these proteins were analysed using RAMPAGE. Further, the blood-brain barrier (BBB) crossing ability of the natural compounds were analysed using cbligand. The <em>In silico </em>ADME (Absorption, Distribution, Metabolism, Excretion) properties of esculin and hinokitol were compared with that of levodopa using molinspiration and admetSAR @ LMMD software.<strong></strong></p><p><strong>Results: </strong>The predictions were that hinokitol, being blood-brain barrier positive (BBB+) with fewer side effects could be a potent anti-PD drug than esculin as it proved to be blood-brain barrier negative (BBB-). Hinokitol was predicted to be good inhibitors of AS, MAO-B and Parkin.</p><p><strong>Conclusion: </strong>The study revealed that hinokitol could be a potent anti-PD drug, being BBB+. Hinokitol was additionally predicted as a good inhibitor of AS, MAO-B and Parkin than levodopa standard.</p><p> </p>

Design, Synthesis, and Antileukemic Evaluation of a Novel Mikanolide Derivative Through the Ras/Raf/MEK/ERK Pathway

“…The molecular docking simulation was performed via the AutoDock Vina program (Morris et al, 2009;Varier et al, 2017). ERK (PDB code: 5V60) interaction with U0126 (PubChem ID: 3006531) and 3g were carefully analyzed.…”