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Structure-based design and analysis of MAO-B inhibitors for Parkinson’s disease: using in silico approaches

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Abstract

Parkinson’s disease (PD) is a degenerative disorder of the CNS, characterized by cerebral depletion of dopamine (DA), hence one of the approaches to delay the depletion of DA is to inhibit its oxidative deamination. Monoamine oxidases (MAO) carry out the oxidative deamination of monoamines like DA. These are intracellular enzymes, located on the outer mitochondrial membrane. MAO-A and MAO-B are the two subtypes of which MAO-B is the most predominant enzyme and is commonly found in the brain. Inhibition of the MAO-B enzyme boosts the effect of both endogenous and exogenous DA. In this study, we have carried out crystal structure analysis and structure-based design of MAO-B inhibitors. We also performed molecular dynamics, flexible docking, induced-fit docking and ADME prediction of the newly designed compounds.

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Acknowledgments

The authors would like to thank the Department of Science and Technology (DST) and the Council of Scientific and Industrial Research (CSIR), New Delhi, India for their financial assistance.

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Authors and Affiliations

  1. Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar (Mohali), 160062, Punjab, India

    Pavan Kare, Jyotsna Bhat & M. Elizabeth Sobhia

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  1. Pavan Kare
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  2. Jyotsna Bhat
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  3. M. Elizabeth Sobhia
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Correspondence to M. Elizabeth Sobhia.

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Kare, P., Bhat, J. & Sobhia, M.E. Structure-based design and analysis of MAO-B inhibitors for Parkinson’s disease: using in silico approaches. Mol Divers 17, 111–122 (2013). https://doi.org/10.1007/s11030-012-9420-z

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