Objective: This study aims to identify novel dopamine D2 receptor agonists through the computational drug discovery pipeline.

Background: Parkinson’s disease (PD) is a neurodegenerative disorder that has emerged as one of the most serious health issues of the twenty-first century. Because of the formation of by-products (Lewy bodies) and the lack of a dopamine neurotransmitter, it affects the nigrostriatal pathway in the brain. Bradykinesia, tremor, rigidity, and postural instability are some of the clinical manifestations. Non-motor symptoms, such as cognitive impairment and emotional and behavioural dysfunction, are also common. Dopamine receptor agonists are commonly used medications in the treatment of Parkinson’s disease. However, the available drugs have limited efficacy and are associated with serious side effects, just like all other medications currently available to treat Parkinson’s disease. As a result, there is an urgent need to develop new therapeutic compounds for Parkinson’s disease. 

Method:

The chemical structure in 2D format of compounds present in turmeric imcluding Ar-turmeroone, corymbolone, curucumin, curdione, Xylopropamine etc. and Ropinirole (Standard Drug) were retrieved from PubChem compound database and Dopamine (D2) receptor was retrieved from protein data bank repository. Receptor and ligand preparation was done using Pymol and computational docking analysis was performed using PyRx, AutoDock Vina option based on scoring functions. The AMET properties of the compounds were predicted using AMET 2.0 server.

Results: Xylopropamine has a binding affinity of -14.7 kcal/mol and MMGB/SA binding free energy of -49.78 kcal/mol while the standard compound has a binding energy of -8.0 kcal/mol. The lead compound also has a Molecular Weight (MW) of 163.26 g/mol, the number of hydrogen bond donor is 1, the number of hydrogen bond acceptors is 1, the LogP is 2.78 and the number of rotatable bonds is 2.

Conclusion: Docking studies and ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) properties evaluation of xylopropamine with dopamine D2 receptor showed that this ligand is a drugable molecule which docked well with the receptor. Therefore, xylopropamine plays an important role in stimulating dopamine (D2) receptors and thus should be implicated as a potential therapeutic agent in Parkinson’s disease. 

« Back to 2023 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/identification-of-xylopropamine-as-a-potential-dopamine-d2-receptor-agonist-through-computational-drug-discovery-pipeline/