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In silico studies of natural product-like caffeine derivatives as potential MAO-B inhibitors/AA2AR antagonists for the treatment of Parkinson's disease.
J Integr Bioinform. 2022 Dec 01; 19(4)JI

Abstract

Parkinson's disease is considered the second most frequent neurodegenerative disease. It is described by the loss of dopaminergic neurons in the mid-brain. For many decades, L-DOPA has been considered as the gold standard for treating Parkinson's disease motor symptoms, however, due to the decrease of efficacy, in the long run, there is an urgent need for novel antiparkinsonian drugs. Caffeine derivatives have been reported several times for their neuroprotective properties and dual blockade of monoamine oxidase (MAO) and adenosine A2A receptors (AA2AR). Natural products are currently attracting more focus due to structural diversity and safety in contrast to synthetic drugs. In the present work, computational studies were conducted on natural product-like caffeine derivatives to search for novel potent candidates acting as dual MAO-B inhibitors/AA2AR antagonists for Parkinson's disease. Our findings revealed two natural products among the top hits: CNP0202316 and CNP0365210 fulfill the requirements of drugs acting on the brain. The selected lead compounds were further studied using molecular dynamics simulation to assess their stability with MAO-B. Current findings might shift the interest towards natural-based compounds and could be exploited to further optimize caffeine derivatives into a successful dual-target-directed drug for managing and halting the neuronal damage in Parkinson's disease patients.

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Authors+Show Affiliations

Boulaamane Y
Laboratory of Innovative Technologies, National School of Applied Sciences of Tangier, Abdelmalek Essaadi University, Tetouan, Morocco.
Ibrahim MAA
Computational Chemistry Laboratory, Chemistry Department, Faculty of Science, Minia University, Minia, 61519, Egypt.
Britel MR
Laboratory of Innovative Technologies, National School of Applied Sciences of Tangier, Abdelmalek Essaadi University, Tetouan, Morocco.
Maurady A
Laboratory of Innovative Technologies, National School of Applied Sciences of Tangier, Abdelmalek Essaadi University, Tetouan, Morocco. Faculty of Sciences and Techniques of Tangier, Abdelmalek Essaadi University, Tetouan, Morocco.

MeSH

HumansCaffeineParkinson DiseaseMonoamine Oxidase InhibitorsNeurodegenerative DiseasesAdenosine A2 Receptor AntagonistsMonoamine Oxidase

Pub Type(s)

Journal Article

Language

eng

PubMed ID

36112816

Citation

Boulaamane, Yassir, et al. "In Silico Studies of Natural Product-like Caffeine Derivatives as Potential MAO-B inhibitors/AA2AR Antagonists for the Treatment of Parkinson's Disease." Journal of Integrative Bioinformatics, vol. 19, no. 4, 2022.
Boulaamane Y, Ibrahim MAA, Britel MR, et al. In silico studies of natural product-like caffeine derivatives as potential MAO-B inhibitors/AA2AR antagonists for the treatment of Parkinson's disease. J Integr Bioinform. 2022;19(4).
Boulaamane, Y., Ibrahim, M. A. A., Britel, M. R., & Maurady, A. (2022). In silico studies of natural product-like caffeine derivatives as potential MAO-B inhibitors/AA2AR antagonists for the treatment of Parkinson's disease. Journal of Integrative Bioinformatics, 19(4). https://doi.org/10.1515/jib-2021-0027
Boulaamane Y, et al. In Silico Studies of Natural Product-like Caffeine Derivatives as Potential MAO-B inhibitors/AA2AR Antagonists for the Treatment of Parkinson's Disease. J Integr Bioinform. 2022 Dec 1;19(4) PubMed PMID: 36112816.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In silico studies of natural product-like caffeine derivatives as potential MAO-B inhibitors/AA2AR antagonists for the treatment of Parkinson's disease. AU - Boulaamane,Yassir, AU - Ibrahim,Mahmoud A A, AU - Britel,Mohammed Reda, AU - Maurady,Amal, Y1 - 2022/09/19/ PY - 2021/08/28/received PY - 2022/06/24/accepted PY - 2022/9/17/pubmed PY - 2023/1/3/medline PY - 2022/9/16/entrez KW - ADMET prediction KW - caffeine KW - molecular dynamics simulation KW - natural products KW - neuroprotection KW - structure-based virtual screening JF - Journal of integrative bioinformatics JO - J Integr Bioinform VL - 19 IS - 4 N2 - Parkinson's disease is considered the second most frequent neurodegenerative disease. It is described by the loss of dopaminergic neurons in the mid-brain. For many decades, L-DOPA has been considered as the gold standard for treating Parkinson's disease motor symptoms, however, due to the decrease of efficacy, in the long run, there is an urgent need for novel antiparkinsonian drugs. Caffeine derivatives have been reported several times for their neuroprotective properties and dual blockade of monoamine oxidase (MAO) and adenosine A2A receptors (AA2AR). Natural products are currently attracting more focus due to structural diversity and safety in contrast to synthetic drugs. In the present work, computational studies were conducted on natural product-like caffeine derivatives to search for novel potent candidates acting as dual MAO-B inhibitors/AA2AR antagonists for Parkinson's disease. Our findings revealed two natural products among the top hits: CNP0202316 and CNP0365210 fulfill the requirements of drugs acting on the brain. The selected lead compounds were further studied using molecular dynamics simulation to assess their stability with MAO-B. Current findings might shift the interest towards natural-based compounds and could be exploited to further optimize caffeine derivatives into a successful dual-target-directed drug for managing and halting the neuronal damage in Parkinson's disease patients. SN - 1613-4516 UR - https://www.unboundmedicine.com/medline/citation/36112816/In_silico_studies_of_natural_product_like_caffeine_derivatives_as_potential_MAO_B_inhibitors/AA2AR_antagonists_for_the_treatment_of_Parkinson's_disease_ DB - PRIME DP - Unbound Medicine ER -