Computational Screening and Validation of Suitable Natural Compounds Against Peripheral Metabolism of L-Dopa: An Alternative Approach Towards Treatment of Parkinson’s Disease

Posted: 19 Feb 2020

See all articles by Surya Narayan Rath

Surya Narayan Rath

Odisha University of Agriculture and Technology - Department of Bioinformatics

Manorama Patri

Ravenshaw University - School of Life Sciences

Date Written: February 19, 2020

Abstract

Progressive loss of dopaminergic neurons within substantia nigra pars compacta causes motor related symptoms in Parkinson’s disease (PD). Therefore, administration of exogenous Levodopa (L-DOPA) has become a common practise to maintain the dopamine level within the midbrain which provides symptomatic relief to PD patients. But, peripheral degradation of (L-DOPA) occurs due to enzymatic activity of two major proteins such as Dopa decarboxylase (DDC, E.C. 4.1.1.28) and Catechol-O-methyltransferase (COMT, EC 2.1.1.6) therefore only 1-5% of L-DOPA reaches to dopaminergic neurons. To get rid of this situation, few peripheral DDC inhibitors (Carbidopa or Benserazide) and COMT inhibitors (Entacapone or Tolcapone) are co-supplemented along with L-DOPA therapy to prolong the availability of L-DOPA within the brain. On the contrary, as PD is an irreversible disorder thus continuous use of those synthetic drugs induces threat to patient’s hepatic and cardiac health which has risen as a major problem. Therefore, scientific community have been focused to discover suitable drug like natural compounds as an alternative of synthetic medicines. In this context, the present study is planned for in silico discovery of bioactive compounds and evaluation of their effectiveness as potent inhibitors against human DDC and COMT through virtual screening, molecular docking, ADMET analysis, pharmacophore study, and molecular dynamics simulation. This study identified few potent plant oriented drug like natural compounds with good inhibitory effect against both peripheral COMT and DDC and thus may be extended for further experimental validation to be used as adjuvant therapy in L-DOPA treatment.

Keywords: Parkinson’s disease, levodopa, DDC, COMT, natural compounds

Suggested Citation

Rath, Surya Narayan and Patri, Manorama, Computational Screening and Validation of Suitable Natural Compounds Against Peripheral Metabolism of L-Dopa: An Alternative Approach Towards Treatment of Parkinson’s Disease (February 19, 2020). Proceedings of International Conference on Drug Discovery (ICDD) 2020, Available at SSRN: https://ssrn.com/abstract=3540847

Surya Narayan Rath

Odisha University of Agriculture and Technology - Department of Bioinformatics ( email )

Bhubaneswar, Odisha, 751003
India

Manorama Patri (Contact Author)

Ravenshaw University - School of Life Sciences ( email )

Cuttack, Odisha
India

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