Title:In-silico Prediction of the Beta-carboline Alkaloids Harmine and Harmaline as Potent Drug Candidates for the Treatment of Parkinson’s disease
Volume: 20
Issue: 3
Author(s): Rumpa Banerjee*, Mukesh Kumar, Isha Gaurav*, Sudha Thakur, Abhimanyu Thakur, Kunal Singh, Sanchari Karak, Rajeswar Das and Mohit Chhabra
Affiliation:
- Eminent College of Pharmaceutical Technology, Barasat, Kolkata,India
- Department of Botany, Patna Women’s College, Patna, Bihar,India
Keywords:
Anti-Parkinson's drug, neurodegenerative disease, neuroscience, pharmacology, molecular docking, toxicity profile.
Abstract:
Background: Parkinson’s disease (PD) is a progressive neurodegenerative disease manifested
by core symptoms of loss of motor control and postural instability. Loss of dopaminergic
neurons is the cause of PD, thus enhancing dopamine level by pharmacological treatment is one of
the key treatment strategies for PD. However, the limitations of current treatment strategies open
the possibility of novel drug candidates for the treatment of PD.
Objective: To investigate the anti-PD potential of Harmine and Harmaline. We aim to evaluate the
therapeutic potential of Harmine and Harmaline by in-silico approaches; molecular docking, pharmacokinetic
and Prediction of Activity Spectra for Substances (PASS) analysis were used for evaluating
the therapeutic potential of Harmine and Harmaline and standard drug levodopa (L-DOPA).
Methods: Auto dock vina was used for molecular docking of all three compounds against D2- and
D3- dopamine receptors. The pharmacokinetics (PKs) and toxicity profile were predicted by
pkCSM, and the pharmacological activity was predicted by PASS analysis.
Results: Molecular docking showed a higher binding affinity of Harmine and Harmaline as compared
to L-DOPA, and these results were supported by in-silico pharmacokinetic and toxicity profiling.
Moreover, PASS analysis showed anti-PD activity of Harmine and Harmaline.
Conclusion: Harmine and Harmaline exhibit higher binding affinity towards D2- and D3- dopamine
receptors compared to L-DOPA, and PKs and toxicity profile support their potential as
drug candidates for PD therapy.
