Multi-target Phenylpropanoids Against Epilepsy
- Authors: Rodrigues T.1, Dias A.2, dos Santos A.3, Monteiro A.4, Oliveira M.2, Pires H.2, de Sousa N.4, da Silva Stiebbe Salvadori M.2, Scotti M.4, Scotti L.4
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Affiliations:
- Cheminformatics Laboratory, Institute of Drugs and Medicines Research,, Federal University of Paraíba
- Psychopharmacology Laboratory, Institute of Drugs and Medicines Research, Federal University of Paraíba
- Psychopharmacology Laboratory, Institute of Drugs and Medicines Research, Federal University of Paraíba
- Cheminformatics Laboratory, Institute of Drugs and Medicines Research, Federal University of Paraíba
- Issue: Vol 22, No 13 (2024)
- Pages: 2168-2190
- Section: Neurology
- URL: https://rjpbr.com/1570-159X/article/view/644480
- DOI: https://doi.org/10.2174/1570159X22666240524160126
- ID: 644480
Cite item
Full Text
Abstract
:Epilepsy is a neurological disease with no defined cause, characterized by recurrent epilep- tic seizures. These occur due to the dysregulation of excitatory and inhibitory neurotransmitters in the central nervous system (CNS). Psychopharmaceuticals have undesirable side effects; many patients require more than one pharmacotherapy to control crises. With this in mind, this work emphasizes the discovery of new substances from natural products that can combat epileptic seizures. Using in silico techniques, this review aims to evaluate the antiepileptic and multi-target activity of phenylpropanoid derivatives. Initially, ligand-based virtual screening models (LBVS) were performed with 468 phe- nylpropanoid compounds to predict biological activities. The LBVS were developed for the targets al- pha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), voltage-gated calcium channel T- type (CaV), gamma-aminobutyric acid A (GABAA), gamma-aminobutyric acid transporter type 1 (GAT-1), voltage-gated potassium channel of the Q family (KCNQ), voltage-gated sodium channel (NaV), and N-methyl D-aspartate (NMDA). The compounds that had good results in the LBVS were analyzed for the absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and later, the best molecules were evaluated in the molecular docking consensus. The TR430 com- pound showed the best results in pharmacokinetic parameters; its oral absorption was 99.03%, it did not violate any Lipinski rule, it showed good bioavailability, and no cytotoxicity was observed either from the molecule or from the metabolites in the evaluated parameters. TR430 was able to bind with GABAA (activation) and AMPA (inhibition) targets and demonstrated good binding energy and sig- nificant interactions with both targets. The studied compound showed to be a promising molecule with a possible multi-target activity in both fundamental pharmacological targets for the treatment of epi- lepsy.
Keywords
About the authors
Teresa Rodrigues
Cheminformatics Laboratory, Institute of Drugs and Medicines Research,, Federal University of Paraíba
Email: info@benthamscience.net
Arthur Dias
Psychopharmacology Laboratory, Institute of Drugs and Medicines Research, Federal University of Paraíba
Email: info@benthamscience.net
Aline dos Santos
Psychopharmacology Laboratory, Institute of Drugs and Medicines Research, Federal University of Paraíba
Email: info@benthamscience.net
Alex Monteiro
Cheminformatics Laboratory, Institute of Drugs and Medicines Research, Federal University of Paraíba
Email: info@benthamscience.net
Mayara Oliveira
Psychopharmacology Laboratory, Institute of Drugs and Medicines Research, Federal University of Paraíba
Email: info@benthamscience.net
Hugo Pires
Psychopharmacology Laboratory, Institute of Drugs and Medicines Research, Federal University of Paraíba
Email: info@benthamscience.net
Natália de Sousa
Cheminformatics Laboratory, Institute of Drugs and Medicines Research, Federal University of Paraíba
Email: info@benthamscience.net
Mirian da Silva Stiebbe Salvadori
Psychopharmacology Laboratory, Institute of Drugs and Medicines Research, Federal University of Paraíba
Email: info@benthamscience.net
Marcus Scotti
Cheminformatics Laboratory, Institute of Drugs and Medicines Research, Federal University of Paraíba
Email: info@benthamscience.net
Luciana Scotti
Cheminformatics Laboratory, Institute of Drugs and Medicines Research, Federal University of Paraíba
Author for correspondence.
Email: info@benthamscience.net
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