Bioactive Constituents of Safflower plant as potential inhibitors of mutant Leucine-rich repeat kinase 2 (LRRK2): Docking, Pharmacokinetics properties and Molecular Dynamics studies

Abstract

Background Parkinson’s disease has posed a global health threat with no disease-modifying treatment and prolonged use of available drugs such as Levodopa (L-dopa) causes debilitating side effects. This study focused on adopting in-silico approach to investigate the drug likeliness and pharmacokinetics of some Safflower plant phytochemicals as potential therapeutics. A manually curated library of 120 phytochemicals (from different parts of Safflower plant) was first screened virtually for adherence to the Lipinski’s rule of 5 using the SwissADME server. Binding interactions were studied using Discovery Studio Visualizer. Site-specific docking was performed using AutoDock Vina and the docking parameters were set based on the score of Standard drug. The docking scores were validated by Mcule server. ADMET (Adsorption, distribution, metabolism, excretion and toxicity) properties were predicted using swissadme while carcinogenicity and toxicity were predicted using CarcinoPred-EL and PkCSM tools respectively. MD (Molecular dynamics) simulations were performed in GROMACS for 200ns to estimate the stability of the receptor and the protein – ligand complexes. Results Eight compounds; Serotobenine, Kaempferol, Nb-PCoumaroyltryptamine, N-Coumaroyl Serotonin, N-Feruloylserotonin, Scutellarein, Acacetin and Trans-Chalcone were identified as potential inhibitors of LRRK2 with no or mild toxicity. Molecular dynamics show more stability in molecular recognition to C1B (N-Coumaroyl-Serotonin) compound than C4B (Serotobenine). Conclusion Some of the compounds identified in the Safflower have the potential to be drug candidates for the treatment of Parkinson’s disease caused by mutant LRRK2 (Leucine-rich repeat kinase 2), owing to their recorded low binding energy and stability in the target.

Casuarina glauca branchlets’ extract as a potential treatment for ulcerative colitis: chemical composition, in silico and in vivo studies

“…Furthermore, it was reported that a low energy complex and a compatible ligand can lead to potent activity (Agarwal and Mehrotra, 2016). Consequently, the recent molecular docking studies have demonstrated promising outcomes in terms of the binding affinity between CGBRE components and three targeted proteins, namely, EGFR, LRRK2, and HSP90A, which aligned with previous investigations conducted on these proteins (Mohamed et al, 2022;Omena-Okpowe et al, 2022). These findings suggest that CGBRE may be effective in the prevention or treatment of ulcerative colitis mediated by these proteins.…”